WorldWideScience

Sample records for cancer microrna network

  1. MicroRNA regulation network in colorectal cancer metastasis

    Institute of Scientific and Technical Information of China (English)

    Jiao-Jiao; Zhou; Shu; Zheng; Li-Feng; Sun; Lei; Zheng

    2014-01-01

    Colorectal cancer is the third most common cancer worldwide. Metastasis is a major cause of colorectal cancer-related death. Mechanisms of metastasis remain largely obscure. MicroRNA is one of the most important epigenetic regulators by targeting mRNAs posttranscriptionally. Accumulated evidence has supported its significant role in the metastasis of colorectal cancer, including epithelial-mesenchymal transition and angiogenesis. Dissecting microRNAome potentially identifies specific microRNAs as biomarkers of colorectal cancer metastasis. Better understanding of the complex network of microRNAs in colorectal cancer metastasis provide new insights in the biological process of metastasis and in the potential targets for colorectal cancer therapies and for diagnosis of recurrent and metastatic colorectal cancer.

  2. Genetic variation in microRNA networks: the implications for cancer research

    OpenAIRE

    Ryan, Bríd M.; Ana I Robles; Curtis C Harris

    2010-01-01

    Many studies have highlighted the role that microRNAs have in physiological processes and how their deregulation can lead to cancer. More recently it has been proposed that the presence of single nucleotide polymorphisms in microRNA genes, their processing machinery and target binding sites affects cancer risk, treatment efficacy and patient prognosis. In reviewing this new field of cancer biology, we describe the methodological approaches of these studies and make recommendations for which s...

  3. MicroRNA functional network in pancreatic cancer: From biology to biomarkers of disease

    Indian Academy of Sciences (India)

    Jin Wang; Subrata Sen

    2011-08-01

    MicroRNAs (miRs), the 17- to 25-nucleotide-long non-coding RNAs, regulate expression of approximately 30% of the protein-coding genes at the post-transcriptional level and have emerged as critical components of the complex functional pathway networks controlling important cellular processes, such as proliferation, development, differentiation, stress response' and apoptosis. Abnormal expression levels of miRs, regulating critical cancerassociated pathways, have been implicated to play important roles in the oncogenic processes, functioning both as oncogenes and as tumour suppressor genes. Elucidation of the genetic networks regulated by the abnormally expressing miRs in cancer cells is proving to be extremely significant in understanding the role of these miRs in the induction of malignant-transformation-associated phenotypic changes. As a result, the miRs involved in the oncogenic transformation process are being investigated as novel biomarkers of disease detection and prognosis as well as potential therapeutic targets for human cancers. In this \\article, we review the existing literature in the field documenting the significance of aberrantly expressed miRs in human pancreatic cancer and discuss how the oncogenic miRs may be involved in the genetic networks regulating functional pathways deregulated in this malignancy.

  4. Neural network cascade optimizes microRNA biomarker selection for nasopharyngeal cancer prognosis.

    Science.gov (United States)

    Zhu, Wenliang; Kan, Xuan

    2014-01-01

    MicroRNAs (miRNAs) have been shown to be promising biomarkers in predicting cancer prognosis. However, inappropriate or poorly optimized processing and modeling of miRNA expression data can negatively affect prediction performance. Here, we propose a holistic solution for miRNA biomarker selection and prediction model building. This work introduces the use of a neural network cascade, a cascaded constitution of small artificial neural network units, for evaluating miRNA expression and patient outcome. A miRNA microarray dataset of nasopharyngeal carcinoma was retrieved from Gene Expression Omnibus to illustrate the methodology. Results indicated a nonlinear relationship between miRNA expression and patient death risk, implying that direct comparison of expression values is inappropriate. However, this method performs transformation of miRNA expression values into a miRNA score, which linearly measures death risk. Spearman correlation was calculated between miRNA scores and survival status for each miRNA. Finally, a nine-miRNA signature was optimized to predict death risk after nasopharyngeal carcinoma by establishing a neural network cascade consisting of 13 artificial neural network units. Area under the ROC was 0.951 for the internal validation set and had a prediction accuracy of 83% for the external validation set. In particular, the established neural network cascade was found to have strong immunity against noise interference that disturbs miRNA expression values. This study provides an efficient and easy-to-use method that aims to maximize clinical application of miRNAs in prognostic risk assessment of patients with cancer. PMID:25310846

  5. Neural network cascade optimizes microRNA biomarker selection for nasopharyngeal cancer prognosis.

    Directory of Open Access Journals (Sweden)

    Wenliang Zhu

    Full Text Available MicroRNAs (miRNAs have been shown to be promising biomarkers in predicting cancer prognosis. However, inappropriate or poorly optimized processing and modeling of miRNA expression data can negatively affect prediction performance. Here, we propose a holistic solution for miRNA biomarker selection and prediction model building. This work introduces the use of a neural network cascade, a cascaded constitution of small artificial neural network units, for evaluating miRNA expression and patient outcome. A miRNA microarray dataset of nasopharyngeal carcinoma was retrieved from Gene Expression Omnibus to illustrate the methodology. Results indicated a nonlinear relationship between miRNA expression and patient death risk, implying that direct comparison of expression values is inappropriate. However, this method performs transformation of miRNA expression values into a miRNA score, which linearly measures death risk. Spearman correlation was calculated between miRNA scores and survival status for each miRNA. Finally, a nine-miRNA signature was optimized to predict death risk after nasopharyngeal carcinoma by establishing a neural network cascade consisting of 13 artificial neural network units. Area under the ROC was 0.951 for the internal validation set and had a prediction accuracy of 83% for the external validation set. In particular, the established neural network cascade was found to have strong immunity against noise interference that disturbs miRNA expression values. This study provides an efficient and easy-to-use method that aims to maximize clinical application of miRNAs in prognostic risk assessment of patients with cancer.

  6. Network analysis of microRNAs and their regulation in human ovarian cancer

    KAUST Repository

    Schmeier, Sebastian

    2011-11-03

    Background: MicroRNAs (miRNAs) are small non-coding RNA molecules that repress the translation of messenger RNAs (mRNAs) or degrade mRNAs. These functions of miRNAs allow them to control key cellular processes such as development, differentiation and apoptosis, and they have also been implicated in several cancers such as leukaemia, lung, pancreatic and ovarian cancer (OC). Unfortunately, the specific machinery of miRNA regulation, involving transcription factors (TFs) and transcription co-factors (TcoFs), is not well understood. In the present study we focus on computationally deciphering the underlying network of miRNAs, their targets, and their control mechanisms that have an influence on OC development.Results: We analysed experimentally verified data from multiple sources that describe miRNA influence on diseases, miRNA targeting of mRNAs, and on protein-protein interactions, and combined this data with ab initio transcription factor binding site predictions within miRNA promoter regions. From these analyses, we derived a network that describes the influence of miRNAs and their regulation in human OC. We developed a methodology to analyse the network in order to find the nodes that have the largest potential of influencing the network\\'s behaviour (network hubs). We further show the potentially most influential miRNAs, TFs and TcoFs, showing subnetworks illustrating the involved mechanisms as well as regulatory miRNA network motifs in OC. We find an enrichment of miRNA targeted OC genes in the highly relevant pathways cell cycle regulation and apoptosis.Conclusions: We combined several sources of interaction and association data to analyse and place miRNAs within regulatory pathways that influence human OC. These results represent the first comprehensive miRNA regulatory network analysis for human OC. This suggests that miRNAs and their regulation may play a major role in OC and that further directed research in this area is of utmost importance to enhance

  7. MicroRNA-1 properties in cancer regulatory networks and tumor biology.

    Science.gov (United States)

    Weiss, Martin; Brandenburg, Lars-Ove; Burchardt, Martin; Stope, Matthias B

    2016-08-01

    Short non-coding microRNAs have been identified to orchestrate crucial mechanisms in cancer progression and treatment resistance. MicroRNAs are involved in posttranscriptional modulation of gene expression and therefore represent promising targets for anticancer therapy. As mircoRNA-1 (miR-1) exerted to be predominantly downregulated in the majority of examined tumors, miR-1 is classified to be a tumor suppressor with high potential to diminish tumor development and therapy resistance. Here we review the complex functionality of miR-1 in tumor biology. PMID:27286699

  8. MicroRNA and cancer

    DEFF Research Database (Denmark)

    Jansson, Martin D; Lund, Anders H

    2012-01-01

    biological phenomena and pathologies. The best characterized non-coding RNA family consists in humans of about 1400 microRNAs for which abundant evidence have demonstrated fundamental importance in normal development, differentiation, growth control and in human diseases such as cancer. In this review, we...... summarize the current knowledge and concepts concerning the involvement of microRNAs in cancer, which have emerged from the study of cell culture and animal model systems, including the regulation of key cancer-related pathways, such as cell cycle control and the DNA damage response. Importantly, microRNA...

  9. Therapeutic resistance in cancer: microRNA regulation of EGFR signaling networks

    International Nuclear Information System (INIS)

    Receptor tyrosine kinases (RTKs) such as the epidermal growth factor receptor (EGFR) regulate cellular homeostatic processes. EGFR activates downstream signaling cascades that promote tumor cell survival, proliferation and migration. Dysregulation of EGFR signaling as a consequence of overexpression, amplification and mutation of the EGFR gene occurs frequently in several types of cancers and many become dependent on EGFR signaling to maintain their malignant phenotypes. Consequently, concerted efforts have been mounted to develop therapeutic agents and strategies to effectively inhibit EGFR. However, limited therapeutic benefits to cancer patients have been derived from EGFR-targeted therapies. A well-documented obstacle to improved patient survival is the presence of EGFR-inhibitor resistant tumor cell variants within heterogeneous tumor cell masses. Here, we summarize the mechanisms by which tumors resist EGFR-targeted therapies and highlight the emerging role of microRNAs (miRs) as downstream effector molecules utilized by EGFR to promote tumor initiation, progression and that play a role in resistance to EGFR inhibitors. We also examine evidence supporting the utility of miRs as predictors of response to targeted therapies and novel therapeutic agents to circumvent EGFR-inhibitor resistance mechanisms

  10. Network-Based Approaches to Understand the Roles of miR-200 and Other microRNAs in Cancer.

    Science.gov (United States)

    Bracken, Cameron P; Khew-Goodall, Yeesim; Goodall, Gregory J

    2015-07-01

    microRNAs (miRNA) are well suited to the task of regulating gene expression networks, because any given miRNA has the capacity to target dozens, if not hundreds, of genes. The simultaneous targeting of multiple genes within a pathway may enable miRNAs to more strongly regulate the pathway, or to achieve more subtle control through the targeting of distinct subnetworks of genes. Therefore, as our capacity to discover miRNA targets en masse increases, so must our consideration of the complex networks in which these genes participate. We highlight recent studies in which the comprehensive identification of targets has been used to elucidate miRNA-regulated gene networks in cancer, focusing especially upon miRNAs such as members of the miR-200 family that regulate epithelial-mesenchymal transition (EMT), a reversible phenotypic switch whereby epithelial cells take on the more invasive properties of their mesenchymal counterparts. These studies have expanded our understanding of the roles of miRNAs in EMT, which were already known to form important regulatory loops with key transcription factors to regulate the epithelial or mesenchymal properties of cells. PMID:26069247

  11. Epithelial Plasticity in Cancer: Unmasking a MicroRNA Network for TGF-β-, Notch-, and Wnt-Mediated EMT

    Directory of Open Access Journals (Sweden)

    Eugenio Zoni

    2015-01-01

    Full Text Available Epithelial-to-mesenchymal transition (EMT is a reversible process by which cancer cells can switch from a sessile epithelial phenotype to an invasive mesenchymal state. EMT enables tumor cells to become invasive, intravasate, survive in the circulation, extravasate, and colonize distant sites. Paracrine heterotypic stroma-derived signals as well as paracrine homotypic or autocrine signals can mediate oncogenic EMT and contribute to the acquisition of stem/progenitor cell properties, expansion of cancer stem cells, development of therapy resistance, and often lethal metastatic disease. EMT is regulated by a variety of stimuli that trigger specific intracellular signalling pathways. Altered microRNA (miR expression and perturbed signalling pathways have been associated with epithelial plasticity, including oncogenic EMT. In this review we analyse and describe the interaction between experimentally validated miRs and their target genes in TGF-β, Notch, and Wnt signalling pathways. Interestingly, in this process, we identified a “signature” of 30 experimentally validated miRs and a cluster of validated target genes that seem to mediate the cross talk between TGF-β, Notch, and Wnt signalling networks during EMT and reinforce their connection to the regulation of epithelial plasticity in health and disease.

  12. Key nodes of a microRNA network associated with the integrated mesenchymal subtype of high-grade serous ovarian cancer

    Institute of Scientific and Technical Information of China (English)

    Yan Sun; Da Yang; Wei Zhang; Fei Guo; Marina Bagnoli; Feng-Xia Xue; Bao-Cun Sun; Ilya Shmulevich; Delia Mezzanzanica; Ke-Xin Chen; Anil K. Sood

    2015-01-01

    Metastasis is the main cause of cancer mortality. One of the initiating events of cancer metastasis of epithelial tumors is epithelial-to-mesenchymal transition (EMT), during which cells dedifferentiate from a relatively rigid cell structure/morphology to a flexible and changeable structure/morphology often associated with mesenchymal cells. The presence of EMT in human epithelial tumors is reflected by the increased expression of genes and levels of proteins that are preferentialy present in mesenchymal cels. The combined presence of these genes forms the basis of mesenchymal gene signatures, which are the foundation for classifying a mesenchymal subtype of tumors. Indeed, tumor classification schemes that use clustering analysis of large genomic characterizations, like The Cancer Genome Atlas (TCGA), have defined mesenchymal subtype in a number of cancer types, such as high-grade serous ovarian cancer and glioblastoma. However, recent analyses have shown that gene expression-based classifications of mesenchymal subtypes often do not associate with poor survival. This“paradox” can be ameliorated using integrated analysis that combines multiple data types. We recently found that integrating mRNA and microRNA (miRNA) data revealed an integrated mesenchymal subtype that is consistently associated with poor survival in multiple cohorts of patients with serous ovarian cancer. This network consists of 8 major miRNAs and 214 mRNAs. Among the 8 miRNAs, 4 are known to be regulators of EMT. This review provides a summary of these 8 miRNAs, which were associated with the integrated mesenchymal subtype of serous ovarian cancer.

  13. Novel role of microRNAs in prostate cancer

    Institute of Scientific and Technical Information of China (English)

    YU Jun-jie; XIA Shu-jie

    2013-01-01

    Objective To discuss the novel biomarkers of microRNAs in prostate cancer.Data sources The literatures about microRNAs and prostate cancer cited in this review were obtained mainly from Pubmed published in English from 2004 to 2012.Study selection Original articles regarding the novel role of microRNAs in prostate cancer were selected.Results MicroRNAs play an important role in prostate cancer such as cell differentiation,proliferation,apoptosis,and invasion.Especially microRNAs correlate with prostate cancer cell epithelial-mesenchymal transition (EMT),cancer stem cells (CSCs),drug sensitivity,cancer microenvironment,energy metabolism,androgen independence transformation,and diagnosis prediction.Conclusions MicroRNAs are involved in various aspects of prostate cancer biology.The role of microRNA in the initiation and development of prostate cancer deserves further study.

  14. Resveratrol, MicroRNAs, Inflammation, and Cancer

    Directory of Open Access Journals (Sweden)

    Esmerina Tili

    2011-01-01

    Full Text Available MicroRNAs are short noncoding RNAs that regulate the expression of many target genes posttranscriptionally and are thus implicated in a wide array of cellular and developmental processes. The expression of miR-155 or miR-21 is upregulated during the course of the inflammatory response, but these microRNAs are also considered oncogenes due to their upregulation of expression in several types of tumors. Furthermore, it is now well established that inflammation is associated with the induction or the aggravation of nearly 25% of cancers. Therefore, the above microRNAs are thought to link inflammation and cancer. Recently, resveratrol (trans-3,4′,5-trihydroxystilbene, a natural polyphenol with antioxidant, anti-inflammatory, and anticancer properties, currently at the stage of preclinical studies for human cancer prevention, has been shown to induce the expression of miR-663, a tumor-suppressor and anti-inflammatory microRNA, while downregulating miR-155 and miR-21. In this paper we will discuss how the use of resveratrol in therapeutics may benefit from the preanalyses on the status of expression of miR-155 or miR-21 as well as of TGFβ1. In addition, we will discuss how resveratrol activity might possibly be enhanced by simultaneously manipulating the levels of its key target microRNAs, such as miR-663.

  15. Control of metastatic progression by microRNA regulatory networks.

    Science.gov (United States)

    Pencheva, Nora; Tavazoie, Sohail F

    2013-06-01

    Aberrant microRNA (miRNA) expression is a defining feature of human malignancy. Specific miRNAs have been identified as promoters or suppressors of metastatic progression. miRNAs control metastasis through divergent or convergent regulation of metastatic gene pathways. Some miRNA regulatory networks govern cell-autonomous cancer phenotypes, whereas others modulate the cell-extrinsic composition of the metastatic microenvironment. The use of small RNAs as probes into the molecular and cellular underpinnings of metastasis holds promise for the identification of candidate genes for potential therapeutic intervention. PMID:23728460

  16. MicroRNA Methylation in Colorectal Cancer.

    Science.gov (United States)

    Kaur, Sippy; Lotsari-Salomaa, Johanna E; Seppänen-Kaijansinkko, Riitta; Peltomäki, Päivi

    2016-01-01

    Epigenetic alterations such as DNA methylation, histone modifications and non-coding RNA (including microRNA) associated gene silencing have been identified as a major characteristic in human cancers. These alterations may occur more frequently than genetic mutations and play a key role in silencing tumor suppressor genes or activating oncogenes, thereby affecting multiple cellular processes. In recent years, studies have shown that microRNAs, that act as posttranscriptional regulators of gene expression are frequently deregulated in colorectal cancer (CRC), via aberrant DNA methylation. Over the past decade, technological advances have revolutionized the field of epigenetics and have led to the identification of numerous epigenetically dysregulated miRNAs in CRC, which are regulated by CpG island hypermethylation and DNA hypomethylation. In addition, aberrant DNA methylation of miRNA genes holds a great promise in several clinical applications such as biomarkers for early screening, prognosis, and therapeutic applications in CRC. PMID:27573897

  17. Characteristics of microRNA co-target networks

    Science.gov (United States)

    Lee, Chang-Yong

    2011-07-01

    The database of microRNAs and their predicted target genes in humans were used to extract a microRNA co-target network. Based on the finding that more than two miRNAs can target the same gene, we constructed a microRNA co-target network and analyzed it from the perspective of the complex network. We found that a network having a positive assortative mixing can be characterized by small-world and scale-free characteristics which are found in most complex networks. The network was further analyzed by the nearest-neighbor average connectivity, and it was shown that the more assortative a microRNA network is, the wider the range of increasing average connectivity. In particular, an assortative network has a power-law relationship of the average connectivity with a positive exponent. A percolation analysis of the network showed that, although the network is diluted, there is no percolation transition in the network. From these findings, we infer that the microRNAs in the network are clustered together, forming a core group. The same analyses carried out on different species confirmed the robustness of the main results found in the microRNA networks of humans.

  18. MicroRNA Polymorphisms in Cancer: A Literature Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Pipan, Veronika; Zorc, Minja; Kunej, Tanja, E-mail: tanja.kunej@bf.uni-lj.si [Department of Animal Science, Biotechnical Faculty, University of Ljubljana, Groblje 3, SI-1230 Domzale (Slovenia)

    2015-09-09

    Single nucleotide polymorphisms (SNPs) located in microRNA (miRNA) genes (miR-SNPs) have attracted increasing attention in recent years due to their involvement in the development of various types of cancer. Therefore, a systematic review on this topic was needed. From 55 scientific publications we collected 20 SNPs, which are located within 18 miRNA encoding genes and have been associated with 16 types of cancer. Among 20 miRNA gene polymorphisms 13 are located within the premature miRNA region, five within mature, and two within mature seed miRNA region. We graphically visualized a network of miRNA-cancer associations which revealed miRNA genes and cancer types with the highest number of connections. Our study showed that, despite a large number of variations currently known to be located within miRNA genes in humans, most of them have not yet been tested for association with cancer. MicroRNA SNPs collected in this study represent only 0.43% of known miRNA gene variations (20/4687). Results of the present study will be useful to researchers investigating the clinical use of miRNAs, such as the roles of miRNAs as diagnostic markers and therapeutic targets.

  19. MicroRNA Polymorphisms in Cancer: A Literature Analysis

    International Nuclear Information System (INIS)

    Single nucleotide polymorphisms (SNPs) located in microRNA (miRNA) genes (miR-SNPs) have attracted increasing attention in recent years due to their involvement in the development of various types of cancer. Therefore, a systematic review on this topic was needed. From 55 scientific publications we collected 20 SNPs, which are located within 18 miRNA encoding genes and have been associated with 16 types of cancer. Among 20 miRNA gene polymorphisms 13 are located within the premature miRNA region, five within mature, and two within mature seed miRNA region. We graphically visualized a network of miRNA-cancer associations which revealed miRNA genes and cancer types with the highest number of connections. Our study showed that, despite a large number of variations currently known to be located within miRNA genes in humans, most of them have not yet been tested for association with cancer. MicroRNA SNPs collected in this study represent only 0.43% of known miRNA gene variations (20/4687). Results of the present study will be useful to researchers investigating the clinical use of miRNAs, such as the roles of miRNAs as diagnostic markers and therapeutic targets

  20. Screening key microRNAs for castration-resistant prostate cancer based on miRNA/mRNA functional synergistic network.

    Science.gov (United States)

    Zhu, Jin; Wang, Sugui; Zhang, Wenyu; Qiu, Junyi; Shan, Yuxi; Yang, Dongrong; Shen, Bairong

    2015-12-22

    High-throughput methods have been used to explore the mechanisms by which androgen-sensitive prostate cancer (ASPC) develops into castration-resistant prostate cancer (CRPC). However, it is difficult to interpret cryptic results by routine experimental methods. In this study, we performed systematic and integrative analysis to detect key miRNAs that contribute to CRPC development. From three DNA microarray datasets, we retrieved 11 outlier microRNAs (miRNAs) that had expression discrepancies between ASPC and CRPC using a specific algorithm. Two of the miRNAs (miR-125b and miR-124) have previously been shown to be related to CRPC. Seven out of the other nine miRNAs were confirmed by quantitative PCR (Q-PCR) analysis. MiR-210, miR-218, miR-346, miR-197, and miR-149 were found to be over-expressed, while miR-122, miR-145, and let-7b were under-expressed in CRPC cell lines. GO and KEGG pathway analyses revealed that miR-218, miR-197, miR-145, miR-122, and let-7b, along with their target genes, were found to be involved in the PI3K and AKT3 signaling network, which is known to contribute to CRPC development. We then chose five miRNAs to verify the accuracy of the analysis. The target genes of each miRNA were altered significantly upon transfection of specific miRNA mimics in the C4-2 CRPC cell line, which was consistent with our pathway analysis results. Finally, we hypothesized that miR-218, miR-145, miR-197, miR-149, miR-122, and let-7b may contribute to the development of CRPC through the influence of Ras, Rho proteins, and the SCF complex. Further investigation is needed to verify the functions of the identified novel pathways in CRPC development. PMID:26540468

  1. MicroRNAs and cancer resistance: A new molecular plot.

    Science.gov (United States)

    Fanini, F; Fabbri, M

    2016-05-01

    The most common cause of cancer relapse is drug resistance, acquired or intrinsic, which strongly limits the efficacy of both conventional and new targeted chemotherapy. MicroRNAs (miRNAs) are a growing, large family of short noncoding RNAs frequently dysregulated in malignancies. Although the mechanism of miRNA-mediated drug resistance is not fully understood, an increasing amount of evidence suggests their involvement in the acquisition of tumor cell drug resistance, pointing towards the need for novel and more innovative therapeutic approaches. Use of antagomiRs or mimics can modulate specific miRNAs in order to restore gene networks and signaling pathways, perhaps optimizing chemotherapies by increasing cancer cell sensitivity to drugs. The aim of this review is to provide a state-of-the-art scenario with regard to the most recent discoveries in the field of miRNAs involved in the process of resistance to cancer therapy. PMID:26875151

  2. Genome Wide Expression Profiling of Cancer Cell Lines Cultured in Microgravity Reveals Significant Dysregulation of Cell Cycle and MicroRNA Gene Networks.

    Science.gov (United States)

    Vidyasekar, Prasanna; Shyamsunder, Pavithra; Arun, Rajpranap; Santhakumar, Rajalakshmi; Kapadia, Nand Kishore; Kumar, Ravi; Verma, Rama Shanker

    2015-01-01

    Zero gravity causes several changes in metabolic and functional aspects of the human body and experiments in space flight have demonstrated alterations in cancer growth and progression. This study reports the genome wide expression profiling of a colorectal cancer cell line-DLD-1, and a lymphoblast leukemic cell line-MOLT-4, under simulated microgravity in an effort to understand central processes and cellular functions that are dysregulated among both cell lines. Altered cell morphology, reduced cell viability and an aberrant cell cycle profile in comparison to their static controls were observed in both cell lines under microgravity. The process of cell cycle in DLD-1 cells was markedly affected with reduced viability, reduced colony forming ability, an apoptotic population and dysregulation of cell cycle genes, oncogenes, and cancer progression and prognostic markers. DNA microarray analysis revealed 1801 (upregulated) and 2542 (downregulated) genes (>2 fold) in DLD-1 cultures under microgravity while MOLT-4 cultures differentially expressed 349 (upregulated) and 444 (downregulated) genes (>2 fold) under microgravity. The loss in cell proliferative capacity was corroborated with the downregulation of the cell cycle process as demonstrated by functional clustering of DNA microarray data using gene ontology terms. The genome wide expression profile also showed significant dysregulation of post transcriptional gene silencing machinery and multiple microRNA host genes that are potential tumor suppressors and proto-oncogenes including MIR22HG, MIR17HG and MIR21HG. The MIR22HG, a tumor-suppressor gene was one of the highest upregulated genes in the microarray data showing a 4.4 log fold upregulation under microgravity. Real time PCR validated the dysregulation in the host gene by demonstrating a 4.18 log fold upregulation of the miR-22 microRNA. Microarray data also showed dysregulation of direct targets of miR-22, SP1, CDK6 and CCNA2. PMID:26295583

  3. Integrated analysis of microRNA regulatory network in nasopharyngeal carcinoma with deep sequencing

    OpenAIRE

    Wang, Fan; Lu, Juan; Peng, Xiaohong; Jie WANG; LIU, XIONG; Chen, Xiaomei; Jiang, Yiqi; LI, XIANGPING; Zhang, Bao

    2016-01-01

    Background MicroRNAs (miRNAs) have been shown to play a critical role in the development and progression of nasopharyngeal carcinoma (NPC). Although accumulating studies have been performed on the molecular mechanisms of NPC, the miRNA regulatory networks in cancer progression remain largely unknown. Laser capture microdissection (LCM) and deep sequencing are powerful tools that can help us to detect the integrated view of miRNA-target network. Methods Illumina Hiseq2000 deep sequencing was u...

  4. MicroRNA Related Polymorphisms and Breast Cancer Risk

    DEFF Research Database (Denmark)

    Khan, Sofia; Greco, Dario; Michailidou, Kyriaki;

    2014-01-01

    Genetic variations, such as single nucleotide polymorphisms (SNPs) in microRNAs (miRNA) or in the miRNA binding sites may affect the miRNA dependent gene expression regulation, which has been implicated in various cancers, including breast cancer, and may alter individual susceptibility to cancer...

  5. MicroRNA in rectal cancer

    Science.gov (United States)

    Azizian, Azadeh; Gruber, Jens; Ghadimi, B Michael; Gaedcke, Jochen

    2016-01-01

    In rectal cancer, one of the most common cancers worldwide, the proper staging of the disease determines the subsequent therapy. For those with locally advanced rectal cancer, a neoadjuvant chemoradiotherapy (CRT) is recommended before any surgery. However, response to CRT ranges from complete response (responders) to complete resistance (non-responders). To date we are not able to separate in advance the first group from the second, due to the absence of a valid biomarker. Therefore all patients receive the same therapy regardless of whether they reap benefits. On the other hand almost all patients receive a surgical resection after the CRT, although a watch-and-wait procedure or an endoscopic resection might be sufficient for those who responded well to the CRT. Being highly conserved regulators of gene expression, microRNAs (miRNAs) seem to be promising candidates for biomarkers. Many studies have been analyzing the miRNAs expressed in rectal cancer tissue to determine a specific miRNA profile for the ailment. Unfortunately, there is only a small overlap of identified miRNAs between different studies, posing the question as to whether different methods or differences in tissue storage may contribute to that fact or if the results simply are not reproducible, due to unknown factors with undetected influences on miRNA expression. Other studies sought to find miRNAs which correlate to clinical parameters (tumor grade, nodal stage, metastasis, survival) and therapy response. Although several miRNAs seem to have an impact on the response to CRT or might predict nodal stage, there is still only little overlap between different studies. We here aimed to summarize the current literature on rectal cancer and miRNA expression with respect to the different relevant clinical parameters. PMID:27190581

  6. Identification of Gene and MicroRNA Signatures for Oral Cancer Developed from Oral Leukoplakia

    OpenAIRE

    Guanghui Zhu; Yuan He; Shaofang Yang; Beimin Chen; Min Zhou; Xin-Jian Xu

    2015-01-01

    In clinic, oral leukoplakia (OLK) may develop into oral cancer. However, the mechanism underlying this transformation is still unclear. In this work, we present a new pipeline to identify oral cancer related genes and microRNAs (miRNAs) by integrating both gene and miRNA expression profiles. In particular, we find some network modules as well as their miRNA regulators that play important roles in the development of OLK to oral cancer. Among these network modules, 91.67% of genes and 37.5% of ...

  7. Functional screens for cancer-modulating microRNAs

    OpenAIRE

    Poell, J.B.

    2012-01-01

    MicroRNAs (miRNAs) are small non-coding RNAs that control various cellular processes by inhibiting messenger RNAs (mRNAs) with partially complementary target sites. Many molecular pathways that are commonly perturbed in cancer, are subject to miRNA regulation. Introducing or reconstituting specific miRNAs in cancer cells may disrupt cancer progression, and ameliorate disease outcome. To identify cancer-modulating miRNAs, I created a lentiviral expression library containing the majority of all...

  8. Dysregulation of microRNA biogenesis machinery in cancer.

    Science.gov (United States)

    Hata, Akiko; Kashima, Risa

    2016-01-01

    MicroRNAs (miRNAs) are integral to the gene regulatory network. A single miRNA is capable of controlling the expression of hundreds of protein coding genes and modulate a wide spectrum of biological functions, such as proliferation, differentiation, stress responses, DNA repair, cell adhesion, motility, inflammation, cell survival, senescence and apoptosis, all of which are fundamental to tumorigenesis. Overexpression, genetic amplification, and gain-of-function mutation of oncogenic miRNAs ("onco-miRs") as well as genetic deletion and loss-of-function mutation of tumor suppressor miRNAs ("suppressor-miRs") are linked to human cancer. In addition to the dysregulation of a specific onco-miR or suppressor-miRs, changes in global miRNA levels resulting from a defective miRNA biogenesis pathway play a role in tumorigenesis. The function of individual onco-miRs and suppressor-miRs and their target genes in cancer has been described in many different articles elsewhere. In this review, we primarily focus on the recent development regarding the dysregulation of the miRNA biogenesis pathway and its contribution to cancer. PMID:26628006

  9. MicroRNA-126 inhibits the proliferation of lung cancer cell line A549

    Institute of Scientific and Technical Information of China (English)

    Xun Yang; Bei-Bei Chen; Ming-Hua Zhang; Xin-Rong Wang

    2015-01-01

    Objective:To study the role of microRNA-126 in the development of lung cancer.Methods:The biological function of microRNA-126 was detected using EdU assay and CCK-8 assay;the target gene of microRNA-126 was analyzed using real time RT-PCR and Western blot assay.Results: In A549 cell line, overexpression of microRNA-126 inhibits the proliferation rate; VEGF is the target gene of microRNA-126; microRNA-126 exerts its function via regulating VEGF protein level.Conclusions: microRNA-126 inhibits the proliferation in A549 cell line.

  10. Hypoxia-regulated microRNAs in human cancer

    Institute of Scientific and Technical Information of China (English)

    Guomin SHEN; Xiaobo LI; Yong-feng JIA; Gary A PIAZZA; Yaguang XI

    2013-01-01

    Hypoxia plays an important role in the tumor microenvironment by allowing the development and maintenance of cancer cells,but the regulatory mechanisms by which tumor cells adapt to hypoxic conditions are not yet well understood.MicroRNAs are recognized as a new class of master regulators that control gene expression and are responsible for many normal and pathological cellular processes.Studies have shown that hypoxia inducible factor 1 (HIF1) regulates a panel of microRNAs,whereas some of microRNAs target HIF1.The interaction between microRNAs and HIF1 can account for many vital events relevant to tumorigenesis,such as angiogenesis,metabolism,apoptosis,cell cycle regulation,proliferation,metastasis,and resistance to anticancer therapy.This review will summarize recent findings on the roles of hypoxia and microRNAs in human cancer and illustrate the machinery by which microRNAs interact with hypoxia in tumor cells,It is expected to update our knowledge about the regulatory roles of microRNAs in regulating tumor microenvironments and thus benefit the development of new anticancer drugs.

  11. Bladder Cancer Advocacy Network

    Science.gov (United States)

    ... future bladder cancer research through the Patient Survey Network. Read More... Don’t Miss the 2016 BCAN ... Click here for more details Bladder Cancer Advocacy Network 4915 St. Elmo Avenue, Suite 202 Bethesda, Maryland ...

  12. The role of microRNAs in bladder cancer

    OpenAIRE

    ENOKIDA, HIDEKI; YOSHINO, HIROFUMI; Matsushita, Ryosuke; Nakagawa, Masayuki

    2016-01-01

    Bladder cancer (BC) is the fifth most common cancer worldwide and is associated with significant morbidity and mortality. The prognosis of muscle invasive BC is poor, and recurrence is common after radical surgery or chemotherapy. Therefore, new diagnostic methods and treatment modalities are critical. MicroRNAs (miRNAs), a class of small noncoding RNAs, regulate the expression of protein-coding genes by repressing translation or cleaving RNA transcripts in a sequence-specific manner. miRNAs ...

  13. Prognostic microRNAs in cancer tissue from patients operated for pancreatic cancer--five microRNAs in a prognostic index

    DEFF Research Database (Denmark)

    Schultz, Nicolai A; Andersen, Klaus; Roslind, Anne;

    2012-01-01

    The aim of the present study was to identify a panel of microRNAs (miRNAs) that can predict overall survival (OS) in non micro-dissected cancer tissues from patients operated for pancreatic cancer (PC).......The aim of the present study was to identify a panel of microRNAs (miRNAs) that can predict overall survival (OS) in non micro-dissected cancer tissues from patients operated for pancreatic cancer (PC)....

  14. MicroRNAs in Hepatobiliary and Pancreatic Cancers

    Directory of Open Access Journals (Sweden)

    Yoshimasa eSaito

    2011-09-01

    Full Text Available MicroRNAs (miRNAs are small non-coding RNAs that function as endogenous silencers of numerous target genes. Hundreds of human miRNAs have been identified in the human genome. miRNAs are expressed in a tissue-specific manner and play important roles in cell proliferation, apoptosis, and differentiation. Aberrant expression of miRNAs may also contribute to the development and progression of human hepatobiliary and pancreatic cancers. Recent studies have shown that some miRNAs play roles as tumor suppressors or oncogenes in hepatobiliary and pancreatic cancers. miR-122, let-7 family, and miR-101 are downregulated in hepatocellular carcinoma (HCC, suggesting that it is a potential tumor suppressor of HCC. miR-221 and miR-222 are up-regulated in HCC and may act as oncogenic miRNAs in hepatocarcinogenesis. miRNA expression profiling may be a powerful clinical tool for diagnosis and regulation of miRNA expression could be a novel therapeutic strategy for hepatobiliary and pancreatic cancers. In this review, we summarize current knowledge about the roles of important tumor suppressor microRNAs and oncogenic microRNAs in hepatobiliary and pancreatic cancers.

  15. Regulatory MicroRNA Networks: Complex Patterns of Target Pathways for Disease-related and Housekeeping MicroRNAs

    Directory of Open Access Journals (Sweden)

    Sachli Zafari

    2015-06-01

    Full Text Available Blood-based microRNA (miRNA signatures as biomarkers have been reported for various pathologies, including cancer, neurological disorders, cardiovascular diseases, and also infections. The regulatory mechanism behind respective miRNA patterns is only partially understood. Moreover, “preserved” miRNAs, i.e., miRNAs that are not dysregulated in any disease, and their biological impact have been explored to a very limited extent. We set out to systematically determine their role in regulatory networks by defining groups of highly-dysregulated miRNAs that contribute to a disease signature as opposed to preserved housekeeping miRNAs. We further determined preferential targets and pathways of both dysregulated and preserved miRNAs by computing multi-layer networks, which were compared between housekeeping and dysregulated miRNAs. Of 848 miRNAs examined across 1049 blood samples, 8 potential housekeepers showed very limited expression variations, while 20 miRNAs showed highly-dysregulated expression throughout the investigated blood samples. Our approach provides important insights into miRNAs and their role in regulatory networks. The methodology can be applied to systematically investigate the differences in target genes and pathways of arbitrary miRNA sets.

  16. Uncovering growth-suppressive MicroRNAs in lung cancer

    DEFF Research Database (Denmark)

    Liu, Xi; Sempere, Lorenzo F; Galimberti, Fabrizio;

    2009-01-01

    PURPOSE: MicroRNA (miRNA) expression profiles improve classification, diagnosis, and prognostic information of malignancies, including lung cancer. This study uncovered unique growth-suppressive miRNAs in lung cancer. EXPERIMENTAL DESIGN: miRNA arrays were done on normal lung tissues and...... adenocarcinomas from wild-type and proteasome degradation-resistant cyclin E transgenic mice to reveal repressed miRNAs in lung cancer. Real-time and semiquantitative reverse transcription-PCR as well as in situ hybridization assays validated these findings. Lung cancer cell lines were derived from each......-malignant human lung tissue bank. RESULTS: miR-34c, miR-145, and miR-142-5p were repressed in transgenic lung cancers. Findings were confirmed by real-time and semiquantitative reverse transcription-PCR as well as in situ hybridization assays. Similar miRNA profiles occurred in human normal versus malignant lung...

  17. MicroRNAs and Recent Insights into Pediatric Ovarian Cancers

    Directory of Open Access Journals (Sweden)

    Jessica Anne Crawford

    2013-04-01

    Full Text Available Ovarian cancer is the most common pediatric gynecologic malignancy. When diag-nosed in children, ovarian cancers present unique challenges that differ dramatically from those faced by adults. Here, we review the spectrum of ovarian cancers found in young women and girls and discuss the biology of these diseases. A number of advances have re-cently shed significant new understanding on the potential causes of ovarian cancer in this unique population. Particular emphasis is placed on understanding how altered expression of non-coding RNA transcripts known as microRNAs play a key role in the etiology of ovarian germ cell and sex cord-stromal tumors. Emerging transgenic models for these diseases are also reviewed. Lastly, future challenges and opportunities for understanding pediatric ovarian cancers, delineating clinically useful biomarkers and developing targeted therapies are discussed.

  18. MicroRNA-21 regulates stemness in cancer cells

    OpenAIRE

    Kang, Hong-Yo

    2013-01-01

    MicroRNA-21 (miR-21) functions have been linked to cancer progression and chemo- or radiotherapy resistance. While an increasing number of studies have reported a potential role of miR-21 expression in promoting growth of a small population of stem/progenitor cells, knowledge on its role as a regulator of stemness in cancers remains limited. In a previous issue of Stem Cell Research &Therapy, Chung and colleagues provide evidence that miR-21 is highly expressed in stem/progenitor populations ...

  19. Identification of differentially expressed microRNAs in human male breast cancer

    Directory of Open Access Journals (Sweden)

    Schipper Elisa

    2010-03-01

    Full Text Available Abstract Background The discovery of small non-coding RNAs and the subsequent analysis of microRNA expression patterns in human cancer specimens have provided completely new insights into cancer biology. Genetic and epigenetic data indicate oncogenic or tumor suppressor function of these pleiotropic regulators. Therefore, many studies analyzed the expression and function of microRNA in human breast cancer, the most frequent malignancy in females. However, nothing is known so far about microRNA expression in male breast cancer, accounting for approximately 1% of all breast cancer cases. Methods The expression of 319 microRNAs was analyzed in 9 primary human male breast tumors and in epithelial cells from 15 male gynecomastia specimens using fluorescence-labeled bead technology. For identification of differentially expressed microRNAs data were analyzed by cluster analysis and selected statistical methods. Expression levels were validated for the most up- or down-regulated microRNAs in this training cohort using real-time PCR methodology as well as in an independent test cohort comprising 12 cases of human male breast cancer. Results Unsupervised cluster analysis separated very well male breast cancer samples and control specimens according to their microRNA expression pattern indicating cancer-specific alterations of microRNA expression in human male breast cancer. miR-21, miR519d, miR-183, miR-197, and miR-493-5p were identified as most prominently up-regulated, miR-145 and miR-497 as most prominently down-regulated in male breast cancer. Conclusions Male breast cancer displays several differentially expressed microRNAs. Not all of them are shared with breast cancer biopsies from female patients indicating male breast cancer specific alterations of microRNA expression.

  20. MicroRNA in rectal cancer

    OpenAIRE

    Azizian, Azadeh; Gruber, Jens; Ghadimi, B. Michael; Gaedcke, Jochen

    2016-01-01

    In rectal cancer, one of the most common cancers worldwide, the proper staging of the disease determines the subsequent therapy. For those with locally advanced rectal cancer, a neoadjuvant chemoradiotherapy (CRT) is recommended before any surgery. However, response to CRT ranges from complete response (responders) to complete resistance (non-responders). To date we are not able to separate in advance the first group from the second, due to the absence of a valid biomarker. Therefore all pati...

  1. MicroRNAs and Chinese Medicinal Herbs: New Possibilities in Cancer Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Hong, Ming; Wang, Ning; Tan, Hor Yue [School of Chinese Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong (China); Tsao, Sai-Wah [Department of Anatomy, Li KaShing Faculty of Medicine, The University of Hong Kong, Hong Kong (China); Feng, Yibin, E-mail: yfeng@hku.hk [School of Chinese Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong (China)

    2015-08-24

    In recent decades Chinese medicine has been used worldwide as a complementary and alternative medicine to treat cancer. Plenty of studies have shown that microRNAs (miRNAs) play fundamental roles in many pathological processes, including cancer, while the anti-cancer mechanisms of Chinese medicinal herbs targeting miRNAs also have been extensively explored. Our previous studies and those of others on Chinese medicinal herbs and miRNAs in various cancer models have provided a possibility of new cancer therapies, for example, up-regulating the expression of miR-23a may activate the positive regulatory network of p53 and miR-23a involved in the mechanism underlying the anti-tumor effect of berberine in hepatocellular carcinoma (HCC). In this review, we survey the role of Chinese medicinal herbal products in regulating miRNAs in cancer and the use of mediating miRNAs for cancer treatment. In addition, the controversial roles of herb-derived exogenous miRNAs in cancer treatment are also discussed. It is expected that targeting miRNAs would provide a novel therapeutic approach in cancer therapy by improving overall response and survival outcomes in cancer treatment, especially when combined with conventional therapeutics and Chinese medicinal herbal products.

  2. MicroRNAs and Chinese Medicinal Herbs: New Possibilities in Cancer Therapy

    Directory of Open Access Journals (Sweden)

    Ming Hong

    2015-08-01

    Full Text Available In recent decades Chinese medicine has been used worldwide as a complementary and alternative medicine to treat cancer. Plenty of studies have shown that microRNAs (miRNAs play fundamental roles in many pathological processes, including cancer, while the anti-cancer mechanisms of Chinese medicinal herbs targeting miRNAs also have been extensively explored. Our previous studies and those of others on Chinese medicinal herbs and miRNAs in various cancer models have provided a possibility of new cancer therapies, for example, up-regulating the expression of miR-23a may activate the positive regulatory network of p53 and miR-23a involved in the mechanism underlying the anti-tumor effect of berberine in hepatocellular carcinoma (HCC. In this review, we survey the role of Chinese medicinal herbal products in regulating miRNAs in cancer and the use of mediating miRNAs for cancer treatment. In addition, the controversial roles of herb-derived exogenous miRNAs in cancer treatment are also discussed. It is expected that targeting miRNAs would provide a novel therapeutic approach in cancer therapy by improving overall response and survival outcomes in cancer treatment, especially when combined with conventional therapeutics and Chinese medicinal herbal products.

  3. MicroRNAs and Chinese Medicinal Herbs: New Possibilities in Cancer Therapy

    International Nuclear Information System (INIS)

    In recent decades Chinese medicine has been used worldwide as a complementary and alternative medicine to treat cancer. Plenty of studies have shown that microRNAs (miRNAs) play fundamental roles in many pathological processes, including cancer, while the anti-cancer mechanisms of Chinese medicinal herbs targeting miRNAs also have been extensively explored. Our previous studies and those of others on Chinese medicinal herbs and miRNAs in various cancer models have provided a possibility of new cancer therapies, for example, up-regulating the expression of miR-23a may activate the positive regulatory network of p53 and miR-23a involved in the mechanism underlying the anti-tumor effect of berberine in hepatocellular carcinoma (HCC). In this review, we survey the role of Chinese medicinal herbal products in regulating miRNAs in cancer and the use of mediating miRNAs for cancer treatment. In addition, the controversial roles of herb-derived exogenous miRNAs in cancer treatment are also discussed. It is expected that targeting miRNAs would provide a novel therapeutic approach in cancer therapy by improving overall response and survival outcomes in cancer treatment, especially when combined with conventional therapeutics and Chinese medicinal herbal products

  4. MicroRNAs and Chinese Medicinal Herbs: New Possibilities in Cancer Therapy.

    Science.gov (United States)

    Hong, Ming; Wang, Ning; Tan, Hor Yue; Tsao, Sai-Wah; Feng, Yibin

    2015-01-01

    In recent decades Chinese medicine has been used worldwide as a complementary and alternative medicine to treat cancer. Plenty of studies have shown that microRNAs (miRNAs) play fundamental roles in many pathological processes, including cancer, while the anti-cancer mechanisms of Chinese medicinal herbs targeting miRNAs also have been extensively explored. Our previous studies and those of others on Chinese medicinal herbs and miRNAs in various cancer models have provided a possibility of new cancer therapies, for example, up-regulating the expression of miR-23a may activate the positive regulatory network of p53 and miR-23a involved in the mechanism underlying the anti-tumor effect of berberine in hepatocellular carcinoma (HCC). In this review, we survey the role of Chinese medicinal herbal products in regulating miRNAs in cancer and the use of mediating miRNAs for cancer treatment. In addition, the controversial roles of herb-derived exogenous miRNAs in cancer treatment are also discussed. It is expected that targeting miRNAs would provide a novel therapeutic approach in cancer therapy by improving overall response and survival outcomes in cancer treatment, especially when combined with conventional therapeutics and Chinese medicinal herbal products. PMID:26305257

  5. Genome Wide Expression Profiling of Cancer Cell Lines Cultured in Microgravity Reveals Significant Dysregulation of Cell Cycle and MicroRNA Gene Networks

    OpenAIRE

    Vidyasekar, Prasanna; Shyamsunder, Pavithra; Arun, Rajpranap; Santhakumar, Rajalakshmi; Kapadia, Nand Kishore; Kumar, Ravi; Verma, Rama Shanker

    2015-01-01

    Zero gravity causes several changes in metabolic and functional aspects of the human body and experiments in space flight have demonstrated alterations in cancer growth and progression. This study reports the genome wide expression profiling of a colorectal cancer cell line-DLD-1, and a lymphoblast leukemic cell line-MOLT-4, under simulated microgravity in an effort to understand central processes and cellular functions that are dysregulated among both cell lines. Altered cell morphology, red...

  6. MicroRNAs as molecular markers in lung cancer

    Directory of Open Access Journals (Sweden)

    Javier Silva

    2013-10-01

    Full Text Available Lung cancer is the most common cause of cancer death in the western world for both men and women. Lung cancer appears to be a perfect candidate for a screening program, since it is the number one cancer killer, it has a long preclinical phase, curative treatment for the minority of patients who are diagnosed early and a target population at risk (smokers and it is also a major economic burden. The earliest approaches to identifying cancer markers were based on preliminary clinical or pathological observations, although molecular biology is a strong candidate for occupying a place among the set of methods. In search of markers, several alterations, such as mutations, loss of heterozygosity, microsatellite instability, DNA methylation, mitochondrial DNA mutations, viral DNA, modified expression of mRNA, miRNA and proteins, and structurally altered proteins have all been analysed. MicroRNAs (miRNA are small RNA molecules, about 19-25 nucleotides long and encoded in genomes of plants, animals, fungi and viruses. It has been reported that miRNAs may have multiple functions in lung development and that aberrant expression of miRNAs could induce lung tumorigenesis. We review here the role of miRNAs in lung tumorigenesis and also as a novel type of biomarker.-----------------------------------Cite this article as:Silva J, Garcia V, Lopez-Gonzalez A, Provencio M. MicroRNAs as molecular markers in lung cancer. Int J Cancer Ther Oncol 2013;1(1:010111. DOI: http://dx.doi.org/10.14319/ijcto.0101.11

  7. Emerging roles of microRNAs in the Wnt signaling network.

    Science.gov (United States)

    Schepeler, Troels

    2013-01-01

    The Wnt signaling network is known to regulate many cellular processes and is of crucial importance during development and in pathological conditions, including cancer. Small noncoding RNAs from the microRNA family (miRNAs) are important elements in the post-transcriptional control of gene expression. In this work, I review the cross talk between miRNAs and the canonical Wnt signaling pathway in various biological processes with particular emphasis on carcinogenesis. Because alterations of miRNA activity and aberrant Wnt signaling are each intimately linked to tumor biology, deciphering the complex interplay between these two regulatory modules is essential to advance our understanding of the integrated functions of miRNAs in signal transduction cascades and develop rational treatment regimens against cancer. PMID:23614621

  8. MicroRNAs in cancers and neurodegenerative disorders

    OpenAIRE

    Saito, Yoshimasa; Saito, Hidetsugu

    2012-01-01

    MicroRNAs (miRNAs) are small non-coding RNAs which function as endogenous silencers of various target genes. miRNAs are expressed in a tissue-specific manner and playing important roles in cell proliferation, apoptosis, and differentiation during mammalian development. Links between miRNAs and the initiation and progression of human diseases including cancer are becoming increasingly apparent. Recent studies have revealed that some miRNAs such as miR-9, miR-29 family, and miR-34 family are di...

  9. Intratumoral Heterogeneity of MicroRNA Expression in Rectal Cancer

    OpenAIRE

    Anne Haahr Mellergaard Eriksen; Rikke Fredslund Andersen; Boye Schnack Nielsen; Flemming Brandt Sørensen; Ane Lindegaard Appelt; Anders Jakobsen; Torben Frøstrup Hansen

    2016-01-01

    Introduction An increasing number of studies have investigated microRNAs (miRNAs) as potential markers of diagnosis, treatment and prognosis. So far, agreement between studies has been minimal, which may in part be explained by intratumoral heterogeneity of miRNA expression. The aim of the present study was to assess the heterogeneity of a panel of selected miRNAs in rectal cancer, using two different technical approaches. Materials and Methods The expression of the investigated miRNAs was an...

  10. PDGF induced microRNA alterations in cancer cells

    OpenAIRE

    Shao, Minghai; Rossi, Simona; Chelladurai, Bhadrani; Shimizu, Masayoshi; Ntukogu, Obiageli; Ivan, Mircea; Calin, George A.; Matei, Daniela

    2011-01-01

    Platelet derived growth factor (PDGF) regulates gene transcription by binding to specific receptors. PDGF plays a critical role in oncogenesis in brain and other tumors, regulates angiogenesis, and remodels the stroma in physiologic conditions. Here, we show by using microRNA (miR) arrays that PDGFs regulate the expression and function of miRs in glioblastoma and ovarian cancer cells. The two PDGF ligands AA and BB affect expression of several miRs in ligand-specific manner; the most robust c...

  11. The therapeutic potential of MicroRNAs in cancer

    DEFF Research Database (Denmark)

    Thorsen, Susanne; Obad, S.; Jensen, N.F.;

    2012-01-01

    MicroRNAs (miRNAs) have been uncovered as important posttranscriptional regulators of nearly every biological process in the cell. Furthermore, mounting evidence implies that miRNAs play key roles in the pathogenesis of cancer and that many miRNAs can function either as oncogenes or tumor...... suppressors. Thus, miRNAs have rapidly emerged as promising targets for the development of novel anticancer therapeutics. The development of miRNA-based cancer therapeutics relies on restoring the activity of tumor suppressor miRNAs using double-stranded miRNA mimics or inhibition of oncogenic miRNAs using...... single-stranded antisense oligonucleotides, termed antimiRs. In the present review, we focus on recent advancements in the discovery and development of miRNA-based cancer therapeutics using these 2 approaches. In addition, we summarize selected studies, in which modulation of miRNA activity in...

  12. Distinct microRNA alterations characterize high- and low-grade bladder cancer.

    OpenAIRE

    Catto, J W F; Miah, S; Owen, H C; Bryant, H.; Myers, K.; Dudziec, E.; Larre, S.; Milo, M.; Rehman, I; Rosario, D. J.; Di Martino, E; Knowles, M. A.; Meuth, M; Harris, A.L.; Hamdy, F C

    2009-01-01

    Urothelial carcinoma of the bladder (UCC) is a common disease that arises by at least two different molecular pathways. The biology of UCC is incompletely understood, making the management of this disease difficult. Recent evidence implicates a regulatory role for microRNA in cancer. We hypothesized that altered microRNA expression contributes to UCC carcinogenesis. To test this hypothesis, we examined the expression of 322 microRNAs and their processing machinery in 78 normal and malignant u...

  13. The Potential of MicroRNAs in Personalized Medicine against Cancers

    OpenAIRE

    Anne Saumet; Anthony Mathelier; Charles-Henri Lecellier

    2014-01-01

    MicroRNAs orchestrate the expression of the genome and impact many, if not all, cellular processes. Their deregulation is thus often causative of human malignancies, including cancers. Numerous studies have implicated microRNAs in the different steps of tumorigenesis including initiation, progression, metastasis, and resistance to chemo/radiotherapies. Thus, microRNAs constitute appealing targets for novel anticancer therapeutic strategies aimed at restoring their expression or function. As m...

  14. MicroRNA signatures as clinical biomarkers in lung cancer

    Directory of Open Access Journals (Sweden)

    Markou A

    2015-05-01

    Full Text Available Athina Markou, Martha Zavridou, Evi S Lianidou Analysis of Circulating Tumor Cells, Lab of Analytical Chemistry, Department of Chemistry, University of Athens, Athens, Greece Abstract: Even if early lung cancer detection has been recently significantly improved, the invasive nature of current diagnostic procedures, and a relatively high percentage of false positives, is limiting the application of modern detection tools. The discovery and clinical evaluation of novel specific and robust non-invasive biomarkers for diagnosis of lung cancer at an early stage, as well as for better prognosis and prediction of therapy response, is very challenging. MicroRNAs (miRNAs can play an important role in the diagnosis and management of lung cancer patients, as important and reliable biomarkers for cancer detection and prognostic prediction, and even as promising as novel targets for cancer therapy. miRNAs are important in cancer pathogenesis, and deregulation of their expression levels has been detected not only in lung cancer but in many other human tumor types. Numerous studies strongly support the potential of miRNAs as biomarkers in non-small-cell lung cancer, and there is increasing evidence that altered miRNA expression is associated with tumor progression and survival. It is worth mentioning also that detection of miRNAs circulating in plasma or serum has enormous potential, because miRNAs serve as non-invasive biomarkers not only for the diagnosis and prognosis of the disease, but also as novel response and sensitivity predictors for cancer treatment. In this review, we summarize the current findings on the critical role of miRNAs in lung cancer tumorigenesis and highlight their potential as circulating biomarkers in lung cancer. Our review is based on papers that have been published after 2011, and includes the key words “miRNAs” and “lung cancer”. Keywords: non-small-cell lung carcinoma, miRNAs, tumor biomarkers, circulating miRNAs, liquid

  15. Prognostic Role of Common MicroRNA Polymorphisms in Cancers: Evidence from a Meta-Analysis

    OpenAIRE

    Xia, Lingzi; Ren, Yangwu; Fang, Xue; Yin, Zhihua; Li, Xuelian; Wu, Wei; Guan, Peng; Baosen ZHOU

    2014-01-01

    Background The morbidity and mortality of cancer increase remarkably every year. It's a heavy burden for family and society. The detection of prognostic biomarkers can help to improve the theraputic effect and prolong the lifetime of patients. microRNAs have an influential role in cancer prognosis. The results of articles discussing the relationship between microRNA polymorphisms and cancer prognosis are inconsistent. Methods We conduct a meta-analysis of 19 publications concerning the associ...

  16. Therapeutic Use of MicroRNAs in Lung Cancer

    Directory of Open Access Journals (Sweden)

    Orazio Fortunato

    2014-01-01

    Full Text Available Lung cancer is a leading cause of cancer deaths worldwide. Although the molecular pathways of lung cancer have been partly known, the high mortality rate is not markedly changed. MicroRNAs (miRNAs are small noncoding RNAs that actively modulate cell physiological processes as apoptosis, cell-cycle control, cell proliferation, DNA repair, and metabolism. Several studies demonstrated that miRNAs are involved in the pathogenesis of lung diseases including lung cancer and they negatively regulate gene and protein expression by acting as oncogenes or tumor suppressors. In this review we summarize the current knowledge on the role of miRNAs and their target genes in lung tumorigenesis and evaluate their potential use as therapeutic agents in lung cancer. In particular, we describe methodological approaches such as inhibition of oncogenic miRNAs or replacement of tumor suppressor miRNAs, both in in vitro and in vivo assays. Furthermore we discuss new strategies to achieve in vivo tissue specific delivery, potential off-target effects, and safety of miRNAs systemic delivery.

  17. Therapeutic evaluation of microRNA-15a and microRNA-16 in ovarian cancer

    Science.gov (United States)

    Dhar Dwivedi, Shailendra Kumar; Mustafi, Soumyajit Banerjee; Mangala, Lingegowda S.; Jiang, Dahai; Pradeep, Sunila; Rodriguez-Aguayo, Cristian; Ling, Hui; Ivan, Cristina; Mukherjee, Priyabrata; Calin, George A.; Lopez-Berestein, Gabriel; Sood, Anil K.; Bhattacharya, Resham

    2016-01-01

    Treatment of chemo-resistant ovarian cancer (OvCa) remains clinically challenging and there is a pressing need to identify novel therapeutic strategies. Here we report that multiple mechanisms that promote OvCa progression and chemo-resistance could be inhibited by ectopic expression of miR-15a and miR-16. Significant correlations between low expression of miR-16, high expression of BMI1 and shortened overall survival (OS) were noted in high grade serous (HGS) OvCa patients upon analysis of The Cancer Genome Atlas (TCGA). Targeting BMI1, in vitro with either microRNA reduced clonal growth of OvCa cells. Additionally, epithelial to mesenchymal transition (EMT) as well as expression of the cisplatin transporter ATP7B were inhibited by miR-15a and miR-16 resulting in decreased degradation of the extra-cellular matrix and enhanced sensitization of OvCa cells to cisplatin. Nanoliposomal delivery of the miR-15a and miR-16 combination, in a pre-clinical chemo-resistant orthotopic mouse model of OvCa, demonstrated striking reduction in tumor burden compared to cisplatin alone. Thus, with the advent of miR replacement therapy some of which are in Phase 2 clinical trials, miR-15a and miR-16 represent novel ammunition in the anti-OvCa arsenal. PMID:26918603

  18. The Roles of MicroRNAs in Breast Cancer

    International Nuclear Information System (INIS)

    MicroRNAs (miRNAs) constitute a large family of small, approximately 20–22 nucleotide, non-coding RNAs that regulate the expression of target genes, mainly at the post-transcriptional level. Accumulating lines of evidence have indicated that miRNAs play important roles in the maintenance of biological homeostasis and that aberrant expression levels of miRNAs are associated with the onset of many diseases, including cancer. In various cancers, miRNAs play important roles in tumor initiation, drug resistance and metastasis. Recent studies reported that miRNAs could also be secreted via small endosome-derived vesicles called exosomes, which are derived from multiple cell types, including dendritic cells, lymphocytes, and tumor cells. Exosomal miRNAs play an important role in cell-to-cell communication and have been investigated as prognostic and diagnostic biomarkers. In this review, we summarize the major findings related to the functions of miRNAs in breast cancer, which is the most frequent cancer in women, and discuss the potential clinical uses of miRNAs, including their roles as therapeutic targets and diagnostic markers

  19. The Roles of MicroRNAs in Breast Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Takahashi, Ryou-u [Division of Molecular and Cellular Medicine, National Cancer Center Research Institute 1-1, Tsukiji 5-chome, Chuo-ku, Tokyo 104-0045 (Japan); Miyazaki, Hiroaki [Division of Molecular and Cellular Medicine, National Cancer Center Research Institute 1-1, Tsukiji 5-chome, Chuo-ku, Tokyo 104-0045 (Japan); Department of Oral and Maxillofacial Surgery, Showa University School of Dentistry, 1-5-8 Hatanodai Shinagawa-ku, Tokyo 142-8555 (Japan); Ochiya, Takahiro, E-mail: tochiya@ncc.go.jp [Division of Molecular and Cellular Medicine, National Cancer Center Research Institute 1-1, Tsukiji 5-chome, Chuo-ku, Tokyo 104-0045 (Japan)

    2015-04-09

    MicroRNAs (miRNAs) constitute a large family of small, approximately 20–22 nucleotide, non-coding RNAs that regulate the expression of target genes, mainly at the post-transcriptional level. Accumulating lines of evidence have indicated that miRNAs play important roles in the maintenance of biological homeostasis and that aberrant expression levels of miRNAs are associated with the onset of many diseases, including cancer. In various cancers, miRNAs play important roles in tumor initiation, drug resistance and metastasis. Recent studies reported that miRNAs could also be secreted via small endosome-derived vesicles called exosomes, which are derived from multiple cell types, including dendritic cells, lymphocytes, and tumor cells. Exosomal miRNAs play an important role in cell-to-cell communication and have been investigated as prognostic and diagnostic biomarkers. In this review, we summarize the major findings related to the functions of miRNAs in breast cancer, which is the most frequent cancer in women, and discuss the potential clinical uses of miRNAs, including their roles as therapeutic targets and diagnostic markers.

  20. MicroRNA related polymorphisms and breast cancer risk.

    Directory of Open Access Journals (Sweden)

    Sofia Khan

    Full Text Available Genetic variations, such as single nucleotide polymorphisms (SNPs in microRNAs (miRNA or in the miRNA binding sites may affect the miRNA dependent gene expression regulation, which has been implicated in various cancers, including breast cancer, and may alter individual susceptibility to cancer. We investigated associations between miRNA related SNPs and breast cancer risk. First we evaluated 2,196 SNPs in a case-control study combining nine genome wide association studies (GWAS. Second, we further investigated 42 SNPs with suggestive evidence for association using 41,785 cases and 41,880 controls from 41 studies included in the Breast Cancer Association Consortium (BCAC. Combining the GWAS and BCAC data within a meta-analysis, we estimated main effects on breast cancer risk as well as risks for estrogen receptor (ER and age defined subgroups. Five miRNA binding site SNPs associated significantly with breast cancer risk: rs1045494 (odds ratio (OR 0.92; 95% confidence interval (CI: 0.88-0.96, rs1052532 (OR 0.97; 95% CI: 0.95-0.99, rs10719 (OR 0.97; 95% CI: 0.94-0.99, rs4687554 (OR 0.97; 95% CI: 0.95-0.99, and rs3134615 (OR 1.03; 95% CI: 1.01-1.05 located in the 3' UTR of CASP8, HDDC3, DROSHA, MUSTN1, and MYCL1, respectively. DROSHA belongs to miRNA machinery genes and has a central role in initial miRNA processing. The remaining genes are involved in different molecular functions, including apoptosis and gene expression regulation. Further studies are warranted to elucidate whether the miRNA binding site SNPs are the causative variants for the observed risk effects.

  1. MicroRNA biomarkers in whole blood for detection of pancreatic cancer

    DEFF Research Database (Denmark)

    Schultz, Nicolai A; Dehlendorff, Christian; Jensen, Benny V;

    2014-01-01

    IMPORTANCE Biomarkers for the early diagnosis of patients with pancreatic cancer are needed to improve prognosis. OBJECTIVES To describe differences in microRNA expression in whole blood between patients with pancreatic cancer, chronic pancreatitis, and healthy participants and to identify panels...... of microRNAs for use in diagnosis of pancreatic cancer compared with the cancer antigen 19-9 (CA19-9). DESIGN, SETTING, AND PARTICIPANTS A case-control study that included 409 patients with pancreatic cancer and 25 with chronic pancreatitis who had been included prospectively in the Danish BIOPAC...... (Biomarkers in Patients with Pancreatic Cancer) study (July 2008-October 2012) plus 312 blood donors as healthy participants. The microRNA expressions in pretreatment whole blood RNA samples were collected and analyzed in 3 randomly determined subcohorts: discovery cohort (143 patients with pancreatic cancer...

  2. SNPing cancer in the bud: microRNA and microRNA-target site polymorphisms as diagnostic and prognostic biomarkers in cancer

    OpenAIRE

    Salzman, David W.; Weidhaas, Joanne B

    2012-01-01

    MicroRNAs are master regulators of gene expression and control many biological pathways such as cell growth, differentiation and apoptosis. Deregulation of microRNA expression and activity results in a myriad of diseases including cancer. Recently, several reports have indicated that single nucleotide polymorphisms (SNPs) in microRNAs and microRNA-target sites impact microRNA biology and associate with cancer risk, treatment response and outcome. In this review we will describe these findings...

  3. MicroRNA expression profiles in human cancer cells after ionizing radiation

    International Nuclear Information System (INIS)

    MicroRNAs are regulators of central cellular processes and are implicated in the pathogenesis and prognosis of human cancers. MicroRNAs also modulate responses to anti-cancer therapy. In the context of radiation oncology microRNAs were found to modulate cell death and proliferation after irradiation. However, changes in microRNA expression profiles in response to irradiation have not been comprehensively analyzed so far. The present study's intend is to present a broad screen of changes in microRNA expression following irradiation of different malignant cell lines. 1100 microRNAs (Sanger miRBase release version 14.0) were analyzed in six malignant cell lines following irradiation with clinically relevant doses of 2.0 Gy. MicroRNA levels 6 hours after irradiation were compared to microRNA levels in non-irradiated cells using the 'Geniom Biochip MPEA homo sapiens'. Hierarchical clustering analysis revealed a pattern, which significantly (p = 0.014) discerned irradiated from non-irradiated cells. The expression levels of a number of microRNAs known to be involved in the regulation of cellular processes like apoptosis, proliferation, invasion, local immune response and radioresistance (e. g. miR-1285, miR-24-1, miR-151-5p, let-7i) displayed 2 - 3-fold changes after irradiation. Moreover, several microRNAs previously not known to be radiation-responsive were discovered. Ionizing radiation induced significant changes in microRNA expression profiles in 3 glioma and 3 squamous cell carcinoma cell lines. The functional relevance of these changes is not addressed but should by analyzed by future work especially focusing on clinically relevant endpoints like radiation induced cell death, proliferation, migration and metastasis

  4. MicroRNA in prostate cancer: Practical aspects.

    Science.gov (United States)

    Patil, Pallavi A; Magi-Galluzzi, Cristina

    2015-12-01

    In the last decade, microRNAs (miRNAs) have emerged as biomarkers for cancer diagnosis, prognosis, therapy and prediction of treatment response and have earned a promising role in prostate cancer (PCa) management. A plethora of studies has been conducted on miRNA expression in PCa compared to non-neoplastic prostatic tissue, in PCa of different histologic grades and pathologic stages, in castration resistance prostate cancer (CRPC), in metastatic disease and in response to therapy, with evidence pointing towards distinctive miRNAs differentially expressed in each of these phases. In addition to tissue, miRNA can be detected in blood, serum, and urine. The aim of this review is to survey studies conducted on human prostate tissue and biofluids and to consolidate trustworthy data on the role of miRNA in the occurrence and progression of PCa, with a delineation of differentially expressed miRNAs and an analysis of their association with PCa prognosis, progression to CRPC and metastatic disease, as well as their correlation with response to chemotherapy and hormonal therapy. Changes in circulating miRNAs may represent potentially useful non-invasive biomarkers for PCa diagnosis, staging and prediction of outcome. PMID:26186079

  5. MicroRNAs in cancer: lessons from melanoma.

    Science.gov (United States)

    Greenberg, Eyal; Nemlich, Yael; Markel, Gal

    2014-01-01

    Melanoma is a high-grade, poorly differentiated malignant tumor of pigment-producing cells (melanocytes), accounting for more than 70% of the skin cancer related deaths. Although new lines of targeted therapy and immunotherapy were introduced lately, durable responses are not common as it is hard to target the elusive metastatic phenotype. microRNAs (miRNAs) are short non-coding RNA molecules that function as specific epigenetic regulators of the transcriptome. miRNAs are involved in a broad spectrum of physiological and pathological processes, including cancer-related functions such as proliferation, cell cycle, migration, invasion, immune evasion and drug resistance. These functions are mostly regulated in melanoma through four molecular deregulated pathways, including the RAS/MAPK pathway, the MITF pathway, the p16INK4A-CDK4-RB pathway and the PI3K-AKT pathway. miRNAs provide a strong platform for delineation of cancer mechanisms. Here we review the diverse roles of miRNAs in melanoma cell biology. Studying miRNA-mediated regulation of aggressive and tumor related features is expected to provide novel mechanistic insights that may pave the way for new diagnostic, prognostic and predictive tools as well as new molecular targets for future therapy. PMID:24479804

  6. Circulating MicroRNAs as Biomarkers in Biliary Tract Cancers

    Science.gov (United States)

    Letelier, Pablo; Riquelme, Ismael; Hernández, Alfonso H.; Guzmán, Neftalí; Farías, Jorge G.; Roa, Juan Carlos

    2016-01-01

    Biliary tract cancers (BTCs) are a group of highly aggressive malignant tumors with a poor prognosis. The current diagnosis is based mainly on imaging and intraoperative exploration due to brush cytology havinga low sensitivity and the standard markers, such as carcinoembryonic antigen (CEA) and carbohydrate 19-9 (CA19-9), not having enough sensitivity nor specificity to be used in a differential diagnosis and early stage detection. Thus, better non-invasive methods that can distinguish between normal and pathological tissue are needed. MicroRNAs (miRNAs) are small, single-stranded non-coding RNA molecules of ~20–22 nucleotides that regulate relevant physiological mechanisms and can also be involved in carcinogenesis. Recent studies have demonstrated that miRNAs are detectable in multiple body fluids, showing great stability, either free or trapped in circulating microvesicles, such as exosomes. miRNAs are ideal biomarkers that may be used in screening and prognosis in biliary tract cancers, aiding also in the clinical decisions at different stages of cancer treatment. This review highlights the progress in the analysis of circulating miRNAs in serum, plasma and bile as potential diagnostic and prognostic markers of BTCs. PMID:27223281

  7. MicroRNA Regulation of Human Breast Cancer Stem Cells

    Directory of Open Access Journals (Sweden)

    Yohei Shimono

    2015-12-01

    Full Text Available MicroRNAs (miRNAs are involved in virtually all biological processes, including stem cell maintenance, differentiation, and development. The dysregulation of miRNAs is associated with many human diseases including cancer. We have identified a set of miRNAs differentially expressed between human breast cancer stem cells (CSCs and non-tumorigenic cancer cells. In addition, these miRNAs are similarly upregulated or downregulated in normal mammary stem/progenitor cells. In this review, we mainly describe the miRNAs that are dysregulated in human breast CSCs directly isolated from clinical specimens. The miRNAs and their clusters, such as the miR-200 clusters, miR-183 cluster, miR-221-222 cluster, let-7, miR-142 and miR-214, target the genes and pathways important for stem cell maintenance, such as the self-renewal gene BMI1, apoptosis, Wnt signaling, Notch signaling, and epithelial-to-mesenchymal transition. In addition, the current evidence shows that metastatic breast CSCs acquire a phenotype that is different from the CSCs in a primary site. Thus, clarifying the miRNA regulation of the metastatic breast CSCs will further advance our understanding of the roles of human breast CSCs in tumor progression.

  8. RNA Helicase DDX5 Regulates MicroRNA Expression and Contributes to Cytoskeletal Reorganization in Basal Breast Cancer Cells

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Daojing; Huang, Jing; Hu, Zhi

    2011-11-15

    RNA helicase DDX5 (also p68) is involved in all aspects of RNA metabolism and serves as a transcriptional co-regulator, but its functional role in breast cancer remains elusive. Here, we report an integrative biology study of DDX5 in breast cancer, encompassing quantitative proteomics, global MicroRNA profiling, and detailed biochemical characterization of cell lines and human tissues. We showed that protein expression of DDX5 increased progressively from the luminal to basal breast cancer cell lines, and correlated positively with that of CD44 in the basal subtypes. Through immunohistochemistry analyses of tissue microarrays containing over 200 invasive human ductal carcinomas, we observed that DDX5 was upregulated in the majority of malignant tissues, and its expression correlated strongly with those of Ki67 and EGFR in the triple-negative tumors. We demonstrated that DDX5 regulated a subset of MicroRNAs including miR-21 and miR-182 in basal breast cancer cells. Knockdown of DDX5 resulted in reorganization of actin cytoskeleton and reduction of cellular proliferation. The effects were accompanied by upregulation of tumor suppressor PDCD4 (a known miR-21 target); as well as upregulation of cofilin and profilin, two key proteins involved in actin polymerization and cytoskeleton maintenance, as a consequence of miR-182 downregulation. Treatment with miR-182 inhibitors resulted in morphologic phenotypes resembling those induced by DDX5 knockdown. Using bioinformatics tools for pathway and network analyses, we confirmed that the network for regulation of actin cytoskeleton was predominantly enriched for the predicted downstream targets of miR-182. Our results reveal a new functional role of DDX5 in breast cancer via the DDX5→miR-182→actin cytoskeleton pathway, and suggest the potential clinical utility of DDX5 and its downstream MicroRNAs in the theranostics of breast cancer.

  9. Arm Selection Preference of MicroRNA-193a Varies in Breast Cancer

    Science.gov (United States)

    Tsai, Kuo-Wang; Leung, Chung-Man; Lo, Yi-Hao; Chen, Ting-Wen; Chan, Wen-Ching; Yu, Shou-Yu; Tu, Ya-Ting; Lam, Hing-Chung; Li, Sung-Chou; Ger, Luo-Ping; Liu, Wen-Shan; Chang, Hong-Tai

    2016-01-01

    MicroRNAs (miRNAs) are short noncoding RNAs derived from the 3′ and 5′ ends of the same precursor. However, the biological function and mechanism of miRNA arm expression preference remain unclear in breast cancer. We found significant decreases in the expression levels of miR-193a-5p but no significant differences in those of miR-193a-3p in breast cancer. MiR-193a-3p suppressed breast cancer cell growth and migration and invasion abilities, whereas miR-193a-5p suppressed cell growth but did not influence cell motility. Furthermore, NLN and CCND1, PLAU, and SEPN1 were directly targeted by miR-193a-5p and miR-193a-3p, respectively, in breast cancer cells. The endogenous levels of miR-193a-5p and miR-193a-3p were significantly increased by transfecting breast cancer cells with the 3′UTR of their direct targets. Comprehensive analysis of The Cancer Genome Atlas database revealed significant differences in the arm expression preferences of several miRNAs between breast cancer and adjacent normal tissues. Our results collectively indicate that the arm expression preference phenomenon may be attributable to the target gene amount during breast cancer progression. The miRNA arm expression preference may be a means of modulating miRNA function, further complicating the mRNA regulatory network. Our findings provide a new insight into miRNA regulation and an application for breast cancer therapy. PMID:27307030

  10. Wnt-signalling pathways and microRNAs network in carcinogenesis: experimental and bioinformatics approaches.

    Science.gov (United States)

    Onyido, Emenike K; Sweeney, Eloise; Nateri, Abdolrahman Shams

    2016-01-01

    Over the past few years, microRNAs (miRNAs) have not only emerged as integral regulators of gene expression at the post-transcriptional level but also respond to signalling molecules to affect cell function(s). miRNAs crosstalk with a variety of the key cellular signalling networks such as Wnt, transforming growth factor-β and Notch, control stem cell activity in maintaining tissue homeostasis, while if dysregulated contributes to the initiation and progression of cancer. Herein, we overview the molecular mechanism(s) underlying the crosstalk between Wnt-signalling components (canonical and non-canonical) and miRNAs, as well as changes in the miRNA/Wnt-signalling components observed in the different forms of cancer. Furthermore, the fundamental understanding of miRNA-mediated regulation of Wnt-signalling pathway and vice versa has been significantly improved by high-throughput genomics and bioinformatics technologies. Whilst, these approaches have identified a number of specific miRNA(s) that function as oncogenes or tumour suppressors, additional analyses will be necessary to fully unravel the links among conserved cellular signalling pathways and miRNAs and their potential associated components in cancer, thereby creating therapeutic avenues against tumours. Hence, we also discuss the current challenges associated with Wnt-signalling/miRNAs complex and the analysis using the biomedical experimental and bioinformatics approaches. PMID:27590724

  11. Prioritization of disease microRNAs through a human phenome-microRNAome network

    Directory of Open Access Journals (Sweden)

    Liu Yunlong

    2010-05-01

    Full Text Available Abstract Background The identification of disease-related microRNAs is vital for understanding the pathogenesis of diseases at the molecular level, and is critical for designing specific molecular tools for diagnosis, treatment and prevention. Experimental identification of disease-related microRNAs poses considerable difficulties. Computational analysis of microRNA-disease associations is an important complementary means for prioritizing microRNAs for further experimental examination. Results Herein, we devised a computational model to infer potential microRNA-disease associations by prioritizing the entire human microRNAome for diseases of interest. We tested the model on 270 known experimentally verified microRNA-disease associations and achieved an area under the ROC curve of 75.80%. Moreover, we demonstrated that the model is applicable to diseases with which no known microRNAs are associated. The microRNAome-wide prioritization of microRNAs for 1,599 disease phenotypes is publicly released to facilitate future identification of disease-related microRNAs. Conclusions We presented a network-based approach that can infer potential microRNA-disease associations and drive testable hypotheses for the experimental efforts to identify the roles of microRNAs in human diseases.

  12. Identification and Pathway Analysis of microRNAs with No Previous Involvement in Breast Cancer

    Science.gov (United States)

    Rebollar-Vega, Rosa; Quintanar-Jurado, Valeria; Maffuz-Aziz, Antonio; Jimenez-Sanchez, Gerardo; Bautista-Piña, Veronica; Arellano-Llamas, Rocio; Hidalgo-Miranda, Alfredo

    2012-01-01

    microRNA expression signatures can differentiate normal and breast cancer tissues and can define specific clinico-pathological phenotypes in breast tumors. In order to further evaluate the microRNA expression profile in breast cancer, we analyzed the expression of 667 microRNAs in 29 tumors and 21 adjacent normal tissues using TaqMan Low-density arrays. 130 miRNAs showed significant differential expression (adjusted P value = 0.05, Fold Change = 2) in breast tumors compared to the normal adjacent tissue. Importantly, the role of 43 of these microRNAs has not been previously reported in breast cancer, including several evolutionary conserved microRNA*, showing similar expression rates to that of their corresponding leading strand. The expression of 14 microRNAs was replicated in an independent set of 55 tumors. Bioinformatic analysis of mRNA targets of the altered miRNAs, identified oncogenes like ERBB2, YY1, several MAP kinases, and known tumor-suppressors like FOXA1 and SMAD4. Pathway analysis identified that some biological process which are important in breast carcinogenesis are affected by the altered microRNA expression, including signaling through MAP kinases and TP53 pathways, as well as biological processes like cell death and communication, focal adhesion and ERBB2-ERBB3 signaling. Our data identified the altered expression of several microRNAs whose aberrant expression might have an important impact on cancer-related cellular pathways and whose role in breast cancer has not been previously described. PMID:22438871

  13. Circulating microRNAs: Novel biomarkers for esophageal cancer

    Directory of Open Access Journals (Sweden)

    Sheng-Li Zhou, Li-Dong Wang

    2010-05-01

    Full Text Available Esophageal carcinogenesis is a multi-stage process, involving a variety of changes in gene expression and physiological structure change. MicroRNAs (miRNAs are a class of small non-coding endogenous RNA molecules. Recent innovation in miRNAs profiling technology have shed new light on the pathology of esophageal carcinoma (EC, and also heralded great potential for exploring novel biomarkers for both EC diagnosis and treatment. Frequent dysregulation of miRNA in malignancy highlights the study of molecular factors upstream of gene expression following the extensive investigation on elucidating the important role of miRNA in carcinogenesis. We herein present a thorough review of the role of miRNAs in EC, addressing miRNA functions, their putative role as oncogenes or tumor suppressors and their potential target genes. The recent progresses in discovering the quantifiable circulating cancer-associated miRNAs indicate the potential clinical use of miRNAs as novel minimally invasive biomarkers for EC and other cancers. We also discuss the potential role of miRNAs in detection, screening and surveillance of EC as miRNAs can be a potential target in personalized treatment of EC.

  14. Computational prediction of microRNA networks incorporating environmental toxicity and disease etiology

    Science.gov (United States)

    Li, Jie; Wu, Zengrui; Cheng, Feixiong; Li, Weihua; Liu, Guixia; Tang, Yun

    2014-07-01

    MicroRNAs (miRNAs) play important roles in multiple biological processes and have attracted much scientific attention recently. Their expression can be altered by environmental factors (EFs), which are associated with many diseases. Identification of the phenotype-genotype relationships among miRNAs, EFs, and diseases at the network level will help us to better understand toxicology mechanisms and disease etiologies. In this study, we developed a computational systems toxicology framework to predict new associations among EFs, miRNAs and diseases by integrating EF structure similarity and disease phenotypic similarity. Specifically, three comprehensive bipartite networks: EF-miRNA, EF-disease and miRNA-disease associations, were constructed to build predictive models. The areas under the receiver operating characteristic curves using 10-fold cross validation ranged from 0.686 to 0.910. Furthermore, we successfully inferred novel EF-miRNA-disease networks in two case studies for breast cancer and cigarette smoke. Collectively, our methods provide a reliable and useful tool for the study of chemical risk assessment and disease etiology involving miRNAs.

  15. Dynamics and pattern formation in a cancer network with diffusion

    Science.gov (United States)

    Zheng, Qianqian; Shen, Jianwei

    2015-10-01

    Diffusion is ubiquitous inside cells, and it is capable of inducing spontaneous pattern formation in reaction-diffusion systems on a spatially homogeneous domain. In this paper, we investigate the dynamics of a diffusive cancer network regulated by microRNA and obtain the condition that the network undergoes a Hopf bifurcation and a Turing pattern bifurcation. In addition, we also develop the amplitude equation of the network model by using Taylor series expansion, multi-scaling and further expansion in powers of a small parameter. As a result of these analyses, we obtain the explicit condition on how the dynamics of the diffusive cancer network evolve. These results reveal that this system has rich dynamics, such as spotted stripe and hexagon patterns. The bifurcation diagram helps us understand the biological mechanism in the cancer network. Finally, numerical simulations confirm our analytical results.

  16. MicroRNAs in Cancer: the 22nd Hiroshima Cancer Seminar/the 4th Japanese Association for RNA Interference Joint International Symposium, 30 August 2012, Grand Prince Hotel Hiroshima.

    Science.gov (United States)

    Tahara, Hidetoshi; Kay, Mark A; Yasui, Wataru; Tahara, Eiichi

    2013-05-01

    The joint international symposium of the 22nd Hiroshima Cancer Seminar and the 4th Japanese Association for RNA Interference focused on a pivotal role of microRNAs in carcinogenesis, progression and therapy of human cancer. Mammalian immune regulator MCPIP1 (Zc3h12a) RNase acts as a novel suppressor of microRNA activity and biogenesis, suggesting the involvement of MCPIP1 in the alteration of microRNA biogenesis in tumorigenesis. Gene set enrichment analysis and functional assignment of microRNAs via enrichment analysis enable the prediction of microRNA activities from mRNA expression data by combining rank-based enrichment analysis and weighted evaluation of microRNA-mRNA interactions. MiR-124 and miR-203 function as tumor-suppressor microRNAs silenced by DNA methylation in hepatocellular carcinoma. Stella-induced DNA hypomethylation would confer the pathogenic function of DNA hypomethylation in cancer. Senescence-associated microRNA, miR-22, suppresses tumor growth and metastasis in vivo in a murine breast cancer model, and exosomal senescence-associated microRNA may affect the tumor microenvironment. The therapeutic potential of microRNAs for preventing and treating lung cancer using the Kras(LSL-G12D/+);p53(LSL-R172H/+)mouse model suggests that miR-34 may be useful in sensitizing tumors to other conventional therapeutics. MiR-1 and miR-133a cluster may function as tumor suppressors regulating novel pathways in human cancers. The down-regulation of miR-148a is implicated in invasion of gastric cancer, while high miR-21 expression in colorectal cancer is associated with poor survival. Neutral sphingomyelinase 2 regulates exosomal microRNA secretion and promotes angiogenesis within the tumor microenvironment as well as metastasis; in particular, the exosomal miR-210 secretion by neutral sphingomyelinase 2 confers the formation of the tumor vessel network. PMID:23487440

  17. Circulating microRNAs are associated with docetaxel chemotherapy outcome in castration-resistant prostate cancer

    OpenAIRE

    Lin, H-M.; Castillo, L.; Mahon, K L; Chiam, K; Lee, B Y; Nguyen, Q.; Boyer, M. J.; Stockler, M R; Pavlakis, N; Marx, G.; Mallesara, G; Gurney, H; Clark, S J; Swarbrick, A; Daly, R. J.

    2014-01-01

    Background: Docetaxel is the first-line chemotherapy for castration-resistant prostate cancer (CRPC). However, response rates are ∼50% and determined quite late in the treatment schedule, thus non-responders are subjected to unnecessary toxicity. The potential of circulating microRNAs as early biomarkers of docetaxel response in CRPC patients was investigated in this study. Methods: Global microRNA profiling was performed on docetaxel-resistant and sensitive cell lines to identify candidate c...

  18. Screening risk microRNAs of ovarian cancer with functional genomics%功能基因组学方法筛选卵巢癌风险 microRNA

    Institute of Scientific and Technical Information of China (English)

    郭秋艳; 张广美

    2012-01-01

    目的:寻找新的卵巢癌发病相关microRNA并为研究人员提供优化后的卵巢癌风险microRNA参照列表.方法:通过在生物网络中度量microRNA靶基因与卵巢癌基因间的功能相似性设计并实现优化卵巢癌风险microRNA计算学方法.采用留一法交叉证实检测该方法的准确性.应用该方法对人类1527个microRNA进行优化排序.结果:留一法交叉证实所得ROC曲线下面积0.92,该方法有着较高的灵敏度和特异度.排序后,一些已知的卵巢癌相关microRNA如let-7、miR-34/200排在了优化结果的前20位.与新一代测序数据结果进行比较,发现排序前20位microRNA中的大部分都在正常和卵巢癌组织中呈差异表达.结论:应用计算学方法可筛选出卵巢癌相关microRNA,并提供优化后的风险microRNA列表.miR-449a等7个未被报道与卵巢癌有关的miRNA有望成为新的卵巢癌相关的风险因子.%Objective: To find new ovarian cancer related microRNAs, provide optimized reference list of ovarian cancer related microRNAs for the researchers. Methods: The optimized computation method of ovarian cancer related microRNAs was designed and realized by measuring the functional similarity of microRNAs target gene and ovarian cancer gene in biological network. Leave - one - out was used to determine the accuracy of the method. The method was used for optimum ranging of 1 527 human raicroRNAs. Results: Leave -one -out confirmed that the area under ROC curve was 0. 92, the method had high sensitivity and specificity. After sequencing, some known ovarian cancer related microRNAs were ranked in lop 20 of the microRNA list, such as let -7 and miR - 34/200. Compared with new sequencing data, the most of top 20 microRNAs expressed in normal ovarian tissue and ovarian cancer tissue differentially. Conclusion: Computation method can screen out ovarian cancer related microRNAs and provide optimized reference list of ovarian cancer related microRNAs. Seven

  19. MicroRNAs: From Female Fertility, Germ Cells, and Stem Cells to Cancer in Humans

    Directory of Open Access Journals (Sweden)

    Irma Virant-Klun

    2016-01-01

    Full Text Available MicroRNAs are a family of naturally occurring small noncoding RNA molecules that play an important regulatory role in gene expression. They are suggested to regulate a large proportion of protein encoding genes by mediating the translational suppression and posttranscriptional control of gene expression. Recent findings show that microRNAs are emerging as important regulators of cellular differentiation and dedifferentiation, and are deeply involved in developmental processes including human preimplantation development. They keep a balance between pluripotency and differentiation in the embryo and embryonic stem cells. Moreover, it became evident that dysregulation of microRNA expression may play a fundamental role in progression and dissemination of different cancers including ovarian cancer. The interest is still increased by the discovery of exosomes, that is, cell-derived vesicles, which can carry different proteins but also microRNAs between different cells and are involved in cell-to-cell communication. MicroRNAs, together with exosomes, have a great potential to be used for prognosis, therapy, and biomarkers of different diseases including infertility. The aim of this review paper is to summarize the existent knowledge on microRNAs related to female fertility and cancer: from primordial germ cells and ovarian function, germinal stem cells, oocytes, and embryos to embryonic stem cells.

  20. A Cancer-Indicative microRNA Pattern in Normal Prostate Tissue

    Directory of Open Access Journals (Sweden)

    Thorsten Schlomm

    2013-03-01

    Full Text Available We analyzed the levels of selected micro-RNAs in normal prostate tissue to assess their potential to indicate tumor foci elsewhere in the prostate. Histologically normal prostate tissue samples from 31 prostate cancer patients and two cancer negative control groups with either unsuspicious or elevated prostate specific antigen (PSA levels (14 and 17 individuals, respectively were analyzed. Based on the expression analysis of 157 microRNAs in a pool of prostate tissue samples and information from data bases/literature, we selected eight microRNAs for quantification by real-time polymerase chain reactions (RT-PCRs. Selected miRNAs were analyzed in histologically tumor-free biopsy samples from patients and healthy controls. We identified seven microRNAs (miR-124a, miR-146a & b, miR-185, miR-16 and let-7a & b, which displayed significant differential expression in normal prostate tissue from men with prostate cancer compared to both cancer negative control groups. Four microRNAs (miR-185, miR-16 and let-7a and let-7b remained to significantly discriminate normal tissues from prostate cancer patients from those of the cancer negative control group with elevated PSA levels. The transcript levels of these microRNAs were highly indicative for the presence of cancer in the prostates, independently of the PSA level. Our results suggest a microRNA-pattern in histologically normal prostate tissue, indicating prostate cancer elsewhere in the organ.

  1. MicroRNAs and Chinese Medicinal Herbs: New Possibilities in Cancer Therapy

    OpenAIRE

    Ming Hong; Ning Wang; Hor Yue Tan; Sai-Wah Tsao; Yibin Feng

    2015-01-01

    In recent decades Chinese medicine has been used worldwide as a complementary and alternative medicine to treat cancer. Plenty of studies have shown that microRNAs (miRNAs) play fundamental roles in many pathological processes, including cancer, while the anti-cancer mechanisms of Chinese medicinal herbs targeting miRNAs also have been extensively explored. Our previous studies and those of others on Chinese medicinal herbs and miRNAs in various cancer models have provided a possibility of ne...

  2. Discovery of microRNA regulatory networks by integrating multidimensional high-throughput data.

    Science.gov (United States)

    Yang, Jian-Hua; Qu, Liang-Hu

    2013-01-01

    MicroRNAs (miRNAs) are endogenous non-coding RNAs (ncRNAs) of approximately 22 nt that regulate the expression of a large fraction of genes by targeting messenger RNAs (mRNAs). However, determining the biologically significant targets of miRNAs is an ongoing challenge. In this chapter, we describe how to identify miRNA-target interactions and miRNA regulatory networks from high-throughput deep sequencing, CLIP-Seq (HITS-CLIP, PAR-CLIP) and degradome sequencing data using starBase platforms. In starBase, several web-based and stand-alone computational tools were developed to discover Argonaute (Ago) binding and cleavage sites, miRNA-target interactions, perform enrichment analysis of miRNA target genes in Gene Ontology (GO) categories and biological pathways, and identify combinatorial effects between Ago and other RNA-binding proteins (RBPs). Investigating target pathways of miRNAs in human CLIP-Seq data, we found that many cancer-associated miRNAs modulate cancer pathways. Performing an enrichment analysis of genes targeted by highly expressed miRNAs in the mouse brain showed that many miRNAs are involved in cancer-associated MAPK signaling and glioma pathways, as well as neuron-associated neurotrophin signaling and axon guidance pathways. Moreover, thousands of combinatorial binding sites between Ago and RBPs were identified from CLIP-Seq data suggesting RBPs and miRNAs coordinately regulate mRNA transcripts. As a means of comprehensively integrating CLIP-Seq and Degradome-Seq data, the starBase platform is expected to identify clinically relevant miRNA-target regulatory relationships, and reveal multi-dimensional post-transcriptional regulatory networks involving miRNAs and RBPs. starBase is available at http://starbase.sysu.edu.cn/ . PMID:23377977

  3. Fluorescence In Situ Hybridization for MicroRNA Detection in Archived Oral Cancer Tissues

    Directory of Open Access Journals (Sweden)

    Zonggao Shi

    2012-01-01

    Full Text Available The noncoding RNA designated as microRNA (miRNA is a large group of small single-stranded regulatory RNA and has generated wide-spread interest in human disease studies. To facilitate delineating the role of microRNAs in cancer pathology, we sought to explore the feasibility of detecting microRNA expression in formalin-fixed paraffin-embedded (FFPE tissues. Using FFPE materials, we have compared fluorescent in situ hybridization (FISH procedures to detect miR-146a with (a different synthetic probes: regular custom DNA oligonucleotides versus locked nucleic acid (LNA incorporated DNA oligonucleotides; (b different reporters for the probes: biotin versus digoxigenin (DIG; (c different visualization: traditional versus tyramide signal amplification (TSA system; (d different blocking reagents for endogenous peroxidase. Finally, we performed miR-146a FISH on a commercially available oral cancer tissue microarray, which contains 40 cases of oral squamous cell carcinoma (OSCC and 10 cases of normal epithelia from the human oral cavity. A sample FISH protocol for detecting miR-146a is provided. In summary, we have established reliable in situ hybridization procedures for detecting the expression of microRNA in FFPE oral cancer tissues. This method is an important tool for studies on the involvement of microRNA in oral cancer pathology and may have potential prognostic or diagnostic value.

  4. Circulating exosomal microRNAs as biomarkers of colon cancer.

    Directory of Open Access Journals (Sweden)

    Hiroko Ogata-Kawata

    Full Text Available PURPOSE: Exosomal microRNAs (miRNAs have been attracting major interest as potential diagnostic biomarkers of cancer. The aim of this study was to characterize the miRNA profiles of serum exosomes and to identify those that are altered in colorectal cancer (CRC. To evaluate their use as diagnostic biomarkers, the relationship between specific exosomal miRNA levels and pathological changes of patients, including disease stage and tumor resection, was examined. EXPERIMENTAL DESIGN: Microarray analyses of miRNAs in exosome-enriched fractions of serum samples from 88 primary CRC patients and 11 healthy controls were performed. The expression levels of miRNAs in the culture medium of five colon cancer cell lines were also compared with those in the culture medium of a normal colon-derived cell line. The expression profiles of miRNAs that were differentially expressed between CRC and control sample sets were verified using 29 paired samples from post-tumor resection patients. The sensitivities of selected miRNAs as biomarkers of CRC were evaluated and compared with those of known tumor markers (CA19-9 and CEA using a receiver operating characteristic analysis. The expression levels of selected miRNAs were also validated by quantitative real-time RT-PCR analyses of an independent set of 13 CRC patients. RESULTS: The serum exosomal levels of seven miRNAs (let-7a, miR-1229, miR-1246, miR-150, miR-21, miR-223, and miR-23a were significantly higher in primary CRC patients, even those with early stage disease, than in healthy controls, and were significantly down-regulated after surgical resection of tumors. These miRNAs were also secreted at significantly higher levels by colon cancer cell lines than by a normal colon-derived cell line. The high sensitivities of the seven selected exosomal miRNAs were confirmed by a receiver operating characteristic analysis. CONCLUSION: Exosomal miRNA signatures appear to mirror pathological changes of CRC patients and

  5. Prognostic Values of microRNAs in Colorectal Cancer

    Directory of Open Access Journals (Sweden)

    Yaguang Xi

    2006-01-01

    Full Text Available The functions of non-coding microRNAs (miRNAs in tumorigenesis are just beginning to emerge. Previous studies from our laboratory have identifi ed a number of miRNAs that were deregulated in colon cancer cell lines due to the deletion of the p53 tumor suppressor gene. In this study, the in vivo signifi cance of some of these miRNAs was further evaluated using colorectal clinical samples. Ten miRNAs (hsa-let-7b, hsa-let-7g, hsa-miR-15b, hsa-miR-181b, hsa-miR-191, hsa-miR-200c, hsa-miR-26a, hsa-miR-27a, hsa-miR-30a-5p and hsa-miR-30c were evaluated for their potential prognostic value in colorectal cancer patients. Forty eight snap frozen clinical colorectal samples (24 colorectal cancer and 24 paired normal patient samples with detailed clinical follow-up information were selected . The expression levels of 10 miRNAs were quantified via qRT-PCR analysis. The statistical signifi cance of these markers for disease prognosis was evaluated using a two tailed paired Wilcoxon test. A Kaplan-Meier survival curve was generated followed by performing a Logrank test. Among the ten miRNAs, hsa-miR-15b (p = 0.0278, hsa-miR-181b (p = 0.0002, hsa-miR-191 (p = 0.0264 and hsa-miR-200c (p = 0.0017 were signifi cantly over-expressed in tumors compared to normal colorectal samples. Kaplan-Meier survival analysis indicated that hsa-miR-200c was signifi cantly associated with patient survival (p = 0.0122. The patients (n = 15 with higher hsa-miR-200c expression had a shorter survival time (median survival = 26 months compared to patients (n = 9 with lower expression (median survival = 38 months. Sequencing analysis revealed that hsa-miR-181b (p = 0.0098 and hsa-miR-200c (p = 0.0322 expression were strongly associated with the mutation status of the p53 tumor suppressor gene. Some of these miRNAs may function as oncogenes due to their over-expression in tumors. hsa-miR-200c may be a potential novel prognostic factor in colorectal cancer.

  6. Profiling of microRNA-mRNA reveals roles of microRNAs in cervical cancer

    Institute of Scientific and Technical Information of China (English)

    MA Ding; ZHANG You-yi; GUO Yan-li; LI Zi-jian; GENG Li

    2012-01-01

    Background Cervical cancer is one of the most common malignant tumors in women.This study was designed to explore the expression profiles of microRNAs (miRNAs) and mRNAs and the gene regulation network in cervical tumorigenesis and to find candidate molecular markers and key tumorigenic genes in cervical cancer.Methods miRNAs and mRNAs expression microarrays were used to detect the expression of miRNAs and mRNAs in normal and cancer cervical tissues.TargetScan 5.0 database (UK) was used to predict the target genes of the miRNAs,analyze their intersection with differentially expressed mRNAs and negatively correlate the intersection with miRNAs.Bioinformatic approaches were used to analyze functions and pathways of the target genes and establish miRNA-gene network.Results Twenty-nine miRNAs and 2036 mRNAs were differentially expressed in normal and cervical tumor tissues.Among them,13 miRNAs and 754 mRNAs were up-regulated in cervical tumor tissues and 16 miRNAs and 1282 RNA were down-regulated.The 327 target genes negatively related to miRNAs in the intersection were involved in functions and signal pathways.Down-regulated miRNAs targeted genes and up-regulated miRNAs targeted genes were involved in 415 and 163 functions,respectively,and in 37 and 17 significant pathways,respectively (P <0.05,false discovery rate (FDR) <0.05).We constructed the miRNAs-gene network and found that hsa-miR-15a,hsa-miR-106b and hsa-miR-20b were key nodes in the network.Conclusions The differentially expressed miRNAs and mRNAs in cervical cancer and related miRNA-gene network have been identified.They play important roles in cervical tumorigenesis and are involved in many important biological functions and signal transduction pathways.These findings lay a foundation for research on the molecular mechanism of miRNAs in the pathogenesis of cervical cancer.

  7. Elevated levels of circulating microRNA-200 family members correlate with serous epithelial ovarian cancer

    Directory of Open Access Journals (Sweden)

    Kan Casina WS

    2012-12-01

    Full Text Available Abstract Background There is a critical need for improved diagnostic markers for high grade serous epithelial ovarian cancer (SEOC. MicroRNAs are stable in the circulation and may have utility as biomarkers of malignancy. We investigated whether levels of serum microRNA could discriminate women with high-grade SEOC from age matched healthy volunteers. Methods To identify microRNA of interest, microRNA expression profiling was performed on 4 SEOC cell lines and normal human ovarian surface epithelial cells. Total RNA was extracted from 500 μL aliquots of serum collected from patients with SEOC (n = 28 and age-matched healthy donors (n = 28. Serum microRNA levels were assessed by quantitative RT-PCR following preamplification. Results microRNA (miR-182, miR-200a, miR-200b and miR-200c were highly overexpressed in the SEOC cell lines relative to normal human ovarian surface epithelial cells and were assessed in RNA extracted from serum as candidate biomarkers. miR-103, miR-92a and miR -638 had relatively invariant expression across all ovarian cell lines, and with small-nucleolar C/D box 48 (RNU48 were assessed in RNA extracted from serum as candidate endogenous normalizers. No correlation between serum levels and age were observed (age range 30-79 years for any of these microRNA or RNU48. Individually, miR-200a, miR-200b and miR-200c normalized to serum volume and miR-103 were significantly higher in serum of the SEOC cohort (P  Conclusions We identified serum microRNAs able to discriminate patients with high grade SEOC from age-matched healthy controls. The addition of these microRNAs to current testing regimes may improve diagnosis for women with SEOC.

  8. Identification of microRNAs associated with tamoxifen resistance in breast cancer

    OpenAIRE

    Lau, Lai-yee.; 劉麗儀.

    2011-01-01

    Tamoxifen is the most widely used endocrine therapy for both early and advanced estrogen receptor (ER) positive breast cancer patients. About half of the patients that initially respond to the antiestrogen become estrogen-independent and ultimately develop resistance to the treatment. The precise molecular mechanisms of tamoxifen resistance remain poorly understood. Dysregulation of microRNAs (miRNAs) has been frequently reported in breast cancer and linked to cancer development, progression...

  9. MicroRNAs and long non-coding RNAs: prospects in diagnostics and therapy of cancer:

    OpenAIRE

    Hauptman, Nina; Glavač, Damjan

    2013-01-01

    Background Non-coding RNAs (ncRNAs) are key regulatory molecules in cellular processes, and are potential biomarkers in many diseases. Currently, microRNAs and long non-coding RNAs are being pursued as diagnostic and prognostic biomarkers, and as therapeutic tools in cancer, since their expression profiling is able to distinguish different cancer types and classify their sub-types. Conclusions There are numerous studies confirming involvement of ncRNAs in cancer initiation, development and pr...

  10. Analysis of microarray-identified genes and microRNAs associated with drug resistance in ovarian cancer.

    Science.gov (United States)

    Zou, Jing; Yin, Fuqiang; Wang, Qi; Zhang, Wei; Li, Li

    2015-01-01

    The aim of this study was to identify potential microRNAs and genes associated with drug resistance in ovarian cancer through web-available microarrays. The drug resistant-related microRNA microarray dataset GS54665 and mRNA dataset GSE33482, GSE28646, and GSE15372 were downloaded from the Gene Expression Omnibus database. Dysregulated microRNAs/genes were screened with GEO2R and were further identified in SKOV3 (SKOV3/DDP) and A2780 (A2780/DDP) cells by real-time quantitative PCR (qRT-PCR), and then their associations with drug resistance was analyzed by comprehensive bioinformatic analyses. Nine microRNAs (microRNA-199a-5p, microRNA-199a-3p, microRNA-199b-3p, microRNA-215, microRNA-335, microRNA-18b, microRNA-363, microRNA-645 and microRNA-141) and 38 genes were identified to be differentially expressed in drug-resistant ovarian cancer cells, with seven genes (NHSL1, EPHA3, USP51, ZSCAN4, EPHA7, SNCA and PI15) exhibited exactly the same expression trends in all three microarrays. Biological process annotation and pathway enrichment analysis of the 9 microRNAs and 38 genes identified several drug resistant-related signaling pathways, and the microRNA-mRNA interaction revealed the existence of a targeted regulatory relationship between the 9 microRNAs and most of the 38 genes. The expression of 9 microRNAs and the 7 genes by qRT-PCR in SKOV3/DDP and A2780/DDP cells indicating a consistent expression profile with the microarrays. Among those, the expression of EPHA7 and PI15 were negatively correlated with that of microRNA-141, and they were also identified as potential targets of this microRNA via microRNA-mRNA interaction. We thus concluded that microRNA-141, EPHA7, and PI15 might jointly participate in the regulation of drug resistance in ovarian cancer and serve as potential targets in targeted therapies. PMID:26261572

  11. Intratumoral Heterogeneity of MicroRNA Expression in Rectal Cancer

    Science.gov (United States)

    Andersen, Rikke Fredslund; Nielsen, Boye Schnack; Sørensen, Flemming Brandt; Appelt, Ane Lindegaard; Jakobsen, Anders; Hansen, Torben Frøstrup

    2016-01-01

    Introduction An increasing number of studies have investigated microRNAs (miRNAs) as potential markers of diagnosis, treatment and prognosis. So far, agreement between studies has been minimal, which may in part be explained by intratumoral heterogeneity of miRNA expression. The aim of the present study was to assess the heterogeneity of a panel of selected miRNAs in rectal cancer, using two different technical approaches. Materials and Methods The expression of the investigated miRNAs was analysed by real-time quantitative polymerase chain reaction (RT-qPCR) and in situ hybridization (ISH) in tumour specimens from 27 patients with T3-4 rectal cancer. From each tumour, tissue from three different luminal localisations was examined. Inter- and intra-patient variability was assessed by calculating intraclass correlation coefficients (ICCs). Correlations between RT-qPCR and ISH were evaluated using Spearman’s correlation. Results ICCsingle (one sample from each patient) was higher than 50% for miRNA-21 and miRNA-31. For miRNA-125b, miRNA-145, and miRNA-630, ICCsingle was lower than 50%. The ICCmean (mean of three samples from each patient) was higher than 50% for miRNA-21(RT-qPCR and ISH), miRNA-125b (RT-qPCR and ISH), miRNA-145 (ISH), miRNA-630 (RT-qPCR), and miRNA-31 (RT-qPCR). For miRNA-145 (RT-qPCR) and miRNA-630 (ISH), ICCmean was lower than 50%. Spearman correlation coefficients, comparing results obtained by RT-qPCR and ISH, respectively, ranged from 0.084 to 0.325 for the mean value from each patient, and from -0.085 to 0.515 in the section including the deepest part of the tumour. Conclusion Intratumoral heterogeneity may influence the measurement of miRNA expression and consequently the number of samples needed for representative estimates. Our findings with two different methods suggest that one sample is sufficient for adequate assessment of miRNA-21 and miRNA-31, whereas more samples would improve the assessment of miRNA-125b, miRNA-145, and miRNA-630

  12. From microRNA functions to microRNA therapeutics: novel targets and novel drugs in breast cancer research and treatment (Review).

    Science.gov (United States)

    Piva, Roberta; Spandidos, Demetrios A; Gambari, Roberto

    2013-10-01

    MicroRNAs (miRNAs or miRs) are a family of small non‑coding RNAs that regulate gene expression by the sequence-selective targeting of mRNAs, leading to translational repression or mRNA degradation, depending on the degree of complementarity with target mRNA sequences. miRNAs play a crucial role in cancer. In the case of breast tumors, several studies have demonstrated a correlation between: i) the expression profile of oncogenic miRNAs (oncomiRs) and tumor suppressor miRNAs; and ii) the tumorigenic potential of triple-negative [estrogen receptor (ER), progesterone receptor (PR) and Her2/neu] primary breast cancers. Among the miRNAs involved in breast cancer, miR-221 plays a crucial role for the following reasons: i) miR-221 is significantly overexpressed in triple-negative primary breast cancer; ii) the oncosuppressor p27Kip1, a validated miR-221 target is downregulated in aggressive cancer cell lines; and iii) the upregulation of a key transcription factor, Slug, appears to be crucial, since it binds to the miR-221/miR-222 promoter and is responsible for the high expression of the miR-221/miR-222 cluster in breast cancer cells. A Slug/miR-221 network has been suggested, linking miR-221 activity with the downregulation of a Slug repressor, leading to Slug/miR-221 upregulation and p27Kip1 downregulation. Interference with this process can be achieved using antisense miRNA (antagomiR) molecules targeting miR-221, inducing the downregulation of Slug and the upregulation of p27Kip1. PMID:23939688

  13. Tumor-Suppressive microRNAs in Lung Cancer: Diagnostic and Therapeutic Opportunities

    OpenAIRE

    Sempere, Lorenzo F; Xi Liu; Ethan Dmitrovsky

    2009-01-01

    Lung cancer is the leading cause of cancer-related death for both men and women in the United States. As for many other cancer types, lung cancer is not a single disease, but rather a variety of diseases that present different histopathological, molecular and clinical characteristics. Improved diagnostic and therapeutic tools are needed to manage and treat lung cancer patients. microRNAs are a recently-discovered class of short non-coding RNAs, which constitutes a novel and functionally-impor...

  14. MicroRNAs as regulators of mitochondrial function: Role in cancer suppression

    Czech Academy of Sciences Publication Activity Database

    Tomasetti, M.; Neužil, Jiří; Dong, L. F.

    2014-01-01

    Roč. 1840, č. 4 (2014), s. 1441-1453. ISSN 0304-4165 R&D Projects: GA ČR(CZ) GAP301/10/1937 Institutional support: RVO:86652036 Keywords : Mitochondrion * MicroRNA * Cancer Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.381, year: 2014

  15. Comparison of MicroRNA Deep Sequencing of Matched Formalin-Fixed Paraffin-Embedded and Fresh Frozen Cancer Tissues

    OpenAIRE

    Wei Meng; McElroy, Joseph P.; Stefano Volinia; Jeff Palatini; Sarah Warner; Ayers, Leona W; Kamalakannan Palanichamy; Arnab Chakravarti; Tim Lautenschlaeger

    2013-01-01

    MicroRNAs regulate several aspects of tumorigenesis and cancer progression. Most cancer tissues are archived formalin-fixed and paraffin-embedded (FFPE). While microRNAs are a more stable form of RNA thought to withstand FFPE-processing and degradation there is only limited evidence for the latter assumption. We examined whether microRNA profiling can be successfully conducted on FFPE cancer tissues using SOLiD ligation based sequencing. Tissue storage times (2-9 years) appeared to not affect...

  16. Identification of a pan-cancer oncogenic microRNA superfamily anchored by a central core seed motif

    Science.gov (United States)

    Hamilton, Mark P.; Rajapakshe, Kimal; Hartig, Sean M.; Reva, Boris; McLellan, Michael D.; Kandoth, Cyriac; Ding, Li; Zack, Travis I.; Gunaratne, Preethi H.; Wheeler, David A.; Coarfa, Cristian; McGuire, Sean E.

    2013-11-01

    MicroRNAs modulate tumorigenesis through suppression of specific genes. As many tumour types rely on overlapping oncogenic pathways, a core set of microRNAs may exist, which consistently drives or suppresses tumorigenesis in many cancer types. Here we integrate The Cancer Genome Atlas (TCGA) pan-cancer data set with a microRNA target atlas composed of publicly available Argonaute Crosslinking Immunoprecipitation (AGO-CLIP) data to identify pan-tumour microRNA drivers of cancer. Through this analysis, we show a pan-cancer, coregulated oncogenic microRNA ‘superfamily’ consisting of the miR-17, miR-19, miR-130, miR-93, miR-18, miR-455 and miR-210 seed families, which cotargets critical tumour suppressors via a central GUGC core motif. We subsequently define mutations in microRNA target sites using the AGO-CLIP microRNA target atlas and TCGA exome-sequencing data. These combined analyses identify pan-cancer oncogenic cotargeting of the phosphoinositide 3-kinase, TGFβ and p53 pathways by the miR-17-19-130 superfamily members.

  17. Current status and implications of microRNAs in ovarian cancer diagnosis and therapy

    Directory of Open Access Journals (Sweden)

    Zaman Mohd Saif

    2012-12-01

    Full Text Available Abstract Ovarian cancer is the fifth most common cancer among women and causes more deaths than any other type of female reproductive cancer. Currently, treatment of ovarian cancer is based on the combination of surgery and chemotherapy. While recurrent ovarian cancer responds to additional chemotherapy treatments, the progression-free interval becomes shorter after each cycle, as chemo-resistance increases until the disease becomes incurable. There is, therefore, a strong need for prognostic and predictive markers to help optimize and personalize treatment in order to improve the outcome of ovarian cancer. An increasing number of studies indicate an essential role for microRNAs in ovarian cancer progression and chemo-resistance. MicroRNAs (miRNAs are small endogenous non-coding RNAs (~22bp which are frequently dysregulated in cancer. Typically, miRNAs are involved in crucial biological processes, including development, differentiation, apoptosis and proliferation. Two families of miRNAs, miR-200 and let-7, are frequently dysregulated in ovarian cancer and have been associated with poor prognosis. Both have been implicated in the regulation of epithelial-to-mesenchymal transition, a cellular transition associated with tumor aggressiveness, tumor invasion and chemo-resistance. Moreover, miRNAs also have possible implications for improving cancer diagnosis; for example miR-200 family, let-7 family, miR-21 and miR-214 may be useful in diagnostic tests to help detect ovarian cancer at an early stage. Additionally, the use of multiple target O-modified antagomirs (MTG-AMO to inhibit oncogenic miRNAs and miRNA replacement therapy for tumor suppressor miRNAs are essential tools for miRNA based cancer therapeutics. In this review we describe the current status of the role miRNAs play in ovarian cancer and focus on the possibilities of microRNA-based therapies and the use of microRNAs as diagnostic tools.

  18. MicroRNAs and the genetic network in aging

    OpenAIRE

    Inukai, Sachi; Slack, Frank

    2013-01-01

    MicroRNAs (miRNAs) comprise a class of small RNAs important for the post-transcriptional regulation of numerous biological processes. Their combinatorial mode of function, in which an individual miRNA can target many genes and multiple miRNAs share targets, makes them especially suited for regulating processes and pathways at the “network” level. In particular, miRNAs have recently been implicated in aging which is a complex process known to involve multiple pathways. Findings from genome-wid...

  19. Quantitative Assessment of the Association between Genetic Variants in MicroRNAs and Colorectal Cancer Risk

    OpenAIRE

    Xiao-Xu Liu; Meng Wang; Dan Xu; Jian-Hai Yang; Hua-Feng Kang; Xi-Jing Wang; Shuai Lin; Peng-Tao Yang; Xing-Han Liu; Zhi-Jun Dai

    2015-01-01

    Background. The associations between polymorphisms in microRNAs and the susceptibility of colorectal cancer (CRC) were inconsistent in previous studies. This study aims to quantify the strength of the correlation between the four common polymorphisms among microRNAs (hsa-mir-146a rs2910164, hsa-mir-149 rs2292832, hsa-mir-196a2 rs11614913, and hsa-mir-499 rs3746444) and CRC risk. Methods. We searched PubMed, Web of Knowledge, and CNKI to find relevant studies. The combined odds ratio (OR) with...

  20. Prognostic Value of MicroRNAs in Preoperative Treated Rectal Cancer

    OpenAIRE

    Azadeh Azizian; Ingo Epping; Frank Kramer; Peter Jo; Markus Bernhardt; Julia Kitz; Gabriela Salinas; Wolff, Hendrik A.; Marian Grade; Tim Beißbarth; B. Michael Ghadimi; Jochen Gaedcke

    2016-01-01

    Background: Patients with locally advanced rectal cancer are treated with preoperative chemoradiotherapy followed by surgical resection. Despite similar clinical parameters (uT2-3, uN+) and standard therapy, patients’ prognoses differ widely. A possible prediction of prognosis through microRNAs as biomarkers out of treatment-naïve biopsies would allow individualized therapy options. Methods: Microarray analysis of 45 microdissected preoperative biopsies from patients with rectal cancer was pe...

  1. MicroRNA-490 inhibits tumorigenesis and progression in breast cancer

    OpenAIRE

    Zhao L; Zheng XY

    2016-01-01

    Lin Zhao,1 Xin-Yu Zheng1,21Department of Breast Surgery, the First Hospital of China Medical University, 2The First Laboratory, Cancer Institute of China Medical University, Shenyang, People’s Republic of ChinaAbstract: MicroRNAs are consistently reported to regulate gene expression in all cancer cell types by modulating a wide range of biological processes, including cell proliferation, differentiation, and apoptosis, which are associated with tumor development and progression. Previou...

  2. Intratumoral Heterogeneity of MicroRNA Expression in Rectal Cancer

    DEFF Research Database (Denmark)

    Eriksen, Anne Haahr Mellergaard; Andersen, Rikke Fredslund; Nielsen, Boye Schnack; Sørensen, Flemming Brandt; Appelt, Ane Lindegaard; Jakobsen, Anders; Hansen, Torben Frøstrup

    2016-01-01

    INTRODUCTION: An increasing number of studies have investigated microRNAs (miRNAs) as potential markers of diagnosis, treatment and prognosis. So far, agreement between studies has been minimal, which may in part be explained by intratumoral heterogeneity of miRNA expression. The aim of the present...

  3. The Role of MicroRNAs as Predictors of Response to Tamoxifen Treatment in Breast Cancer Patients

    Directory of Open Access Journals (Sweden)

    Nina G. Egeland

    2015-10-01

    Full Text Available Endocrine therapy is a key treatment strategy to control or eradicate hormone-responsive breast cancer. However, resistance to endocrine therapy leads to breast cancer relapse. The recent extension of adjuvant tamoxifen treatment up to 10 years actualizes the need for identifying biological markers that may be used to monitor predictors of treatment response. MicroRNAs are promising biomarkers that may fill the gap between preclinical knowledge and clinical observations regarding endocrine resistance. MicroRNAs regulate gene expression by posttranscriptional repression or degradation of mRNA, most often leading to gene silencing. MicroRNAs have been identified directly in the primary tumor, but also in the circulation of breast cancer patients. The few available studies investigating microRNA in patients suggest that seven microRNAs (miR-10a, miR-26, miR-30c, miR-126a, miR-210, miR-342 and miR-519a play a role in tamoxifen resistance. Ingenuity Pathway Analysis (IPA reveals that these seven microRNAs interact more readily with estrogen receptor (ER-independent pathways than ER-related signaling pathways. Some of these pathways are targetable (e.g., PIK3CA, suggesting that microRNAs as biomarkers of endocrine resistance may have clinical value. Validation of the role of these candidate microRNAs in large prospective studies is warranted.

  4. MicroRNA-149 targets GIT1 to suppress integrin signaling and breast cancer metastasis

    OpenAIRE

    Chan, S-H; Huang, W-C; Chang, J-W; Chang, K-J; Kuo, W-H; Wang, M-Y; Lin, K-Y; Uen, Y-H; Hou, M-F; Lin, C-M; Jang, T-H; Tu, C-W; Lee, Y-R; Lee, Y-H; Tien, M-T

    2014-01-01

    Metastasis is the predominant cause of death in breast cancer patients. Several lines of evidence have shown that microRNAs (miRs) can have an important role in cancer metastasis. Using isogenic pairs of low and high metastatic lines derived from a human breast cancer line, we have identified miR-149 to be a suppressor of breast cancer cell invasion and metastasis. We also identified GIT1 (G-protein-coupled receptor kinase-interacting protein 1) as a direct target of miR-149. Knockdown of GIT...

  5. Emerging Evidence for MicroRNAs as Regulators of Cancer Stem Cells

    OpenAIRE

    Sholl, Lynette M.; Aisha Sethi

    2011-01-01

    Cancer stem cells are defined as a subpopulation of cells within a tumor that are capable of self-renewal and differentiation into the heterogeneous cell lineages that comprise the tumor. Many studies indicate that cancer stem cells may be responsible for treatment failure and relapse in cancer patients. The factors that regulate cancer stem cells are not well defined. MicroRNAs (miRNAs) are small non-coding RNAs that regulate translational repression and transcript degradation. miRNAs play a...

  6. MicroRNA-320a promotes 5-FU resistance in human pancreatic cancer cells

    OpenAIRE

    Weibin Wang; Lijun Zhao; Xueju Wei; Lanlan Wang; Siqi Liu; Yu Yang; Fang Wang; Guotao Sun; Junwu Zhang; Yanni Ma; Yupei Zhao; Jia Yu

    2016-01-01

    The drug-resistance of pancreatic cancer cells results in poor therapeutic effect. To predict the therapeutic effect of the chemotherapy drugs to specific patients and to reverse the resistance of pancreatic cancer cells are critical for chemotherapy of pancreatic cancer. MicroRNAs (miRNAs) have been reported to play important roles in the genesis of drug-resistance of various cancer types. There are also many advantages of miRNAs in diagnosis and therapy of disease. Although several miRNAs r...

  7. Performance comparison of digital microRNA profiling technologies applied on human breast cancer cell lines.

    Directory of Open Access Journals (Sweden)

    Erik Knutsen

    Full Text Available MicroRNA profiling represents an important first-step in deducting individual RNA-based regulatory function in a cell, tissue, or at a specific developmental stage. Currently there are several different platforms to choose from in order to make the initial miRNA profiles. In this study we investigate recently developed digital microRNA high-throughput technologies. Four different platforms were compared including next generation SOLiD ligation sequencing and Illumina HiSeq sequencing, hybridization-based NanoString nCounter, and miRCURY locked nucleic acid RT-qPCR. For all four technologies, full microRNA profiles were generated from human cell lines that represent noninvasive and invasive tumorigenic breast cancer. This study reports the correlation between platforms, as well as a more extensive analysis of the accuracy and sensitivity of data generated when using different platforms and important consideration when verifying results by the use of additional technologies. We found all the platforms to be highly capable for microRNA analysis. Furthermore, the two NGS platforms and RT-qPCR all have equally high sensitivity, and the fold change accuracy is independent of individual miRNA concentration for NGS and RT-qPCR. Based on these findings we propose new guidelines and considerations when performing microRNA profiling.

  8. Current status on microRNAs as biomarkers for ovarian cancer.

    Science.gov (United States)

    Prahm, Kira Philipsen; Novotny, Guy Wayne; Høgdall, Claus; Høgdall, Estrid

    2016-05-01

    Ovarian cancer (OC) is the most lethal gynecological malignancy in the Western world, and has a very poor prognosis, often due to late diagnosis and emergence of chemotherapy resistance. Therefore, there is an essential need for new diagnostic and prognostic markers that can improve and initiate more personalized treatment, eventually improving survival of the patients. MicroRNAs are small, non-coding RNA molecules, that post-transcriptionally regulate gene expression. Several studies have within the last decade shown that microRNAs are deregulated in OC and have potential as diagnostic and prognostic biomarkers for OC. Recently studies have also focused on microRNAs as predictors of chemotherapy responses and their potential as therapeutic targets. However, many of the published studies are difficult to interpret as a whole due to various methods of analysis. Future focus should be aimed at developing a general standardized analytical method, which can limit differences between studies thus allowing easier comparison across them. In addition, validation of studies in independent series that ideally should be histotype-specific is essential to determine the clinical role of microRNAs in different types of OC. In this review we summarize the current knowledge of microRNAs as potential biomarkers for OC, with focus on their clinical relevance. PMID:26809719

  9. MicroRNA expression and clinical outcome of small cell lung cancer.

    Directory of Open Access Journals (Sweden)

    Jih-Hsiang Lee

    Full Text Available The role of microRNAs in small-cell lung carcinoma (SCLC is largely unknown. miR-34a is known as a p53 regulated tumor suppressor microRNA in many cancer types. However, its therapeutic implication has never been studied in SCLC, a cancer type with frequent dysfunction of p53. We investigated the expression of a panel of 7 microRNAs (miR-21, miR-29b, miR-34a/b/c, miR-155, and let-7a in 31 SCLC tumors, 14 SCLC cell lines, and 26 NSCLC cell lines. We observed significantly lower miR-21, miR-29b, and miR-34a expression in SCLC cell lines than in NSCLC cell lines. The expression of the 7 microRNAs was unrelated to SCLC patients' clinical characteristics and was neither prognostic in term of overall survival or progression-free survival nor predictive of treatment response. Overexpression or downregulation of miR-34a did not influence SCLC cell viability. The expression of these 7 microRNAs also did not predict in vitro sensitivity to cisplatin or etoposide in SCLC cell lines. Overexpression or downregulation of miR-34a did not influence sensitivity to cisplatin or etoposide in SCLC cell lines. In contrast to downregulation of the miR-34a target genes cMET and Axl by overexpression of miR-34a in NSCLC cell lines, the intrinsic expression of cMET and Axl was low in SCLC cell lines and was not influenced by overexpression of miR-34a. Our results suggest that the expression of the 7 selected microRNAs are not prognostic in SCLC patients, and miR-34a is unrelated to the malignant behavior of SCLC cells and is unlikely to be a therapeutic target.

  10. MicroRNA modulation combined with sunitinib as a novel therapeutic strategy for pancreatic cancer

    Directory of Open Access Journals (Sweden)

    Passadouro M

    2014-07-01

    Full Text Available Marta Passadouro,1,2 Maria C Pedroso de Lima,1,2 Henrique Faneca11Center for Neuroscience and Cell Biology, 2Department of Life Sciences, Faculty of Science and Technology, University of Coimbra, Coimbra, PortugalAbstract: Pancreatic ductal adenocarcinoma (PDAC is a highly aggressive and mortal cancer, characterized by a set of known mutations, invasive features, and aberrant microRNA expression that have been associated with hallmark malignant properties of PDAC. The lack of effective PDAC treatment options prompted us to investigate whether microRNAs would constitute promising therapeutic targets toward the generation of a gene therapy approach with clinical significance for this disease. In this work, we show that the developed human serum albumin–1-palmitoyl-2-oleoyl-sn-glycero-3-ethylphosphocholine:cholesterol/anti-microRNA oligonucleotides (+/– (4/1 nanosystem exhibits the ability to efficiently deliver anti-microRNA oligonucleotides targeting the overexpressed microRNAs miR-21, miR-221, miR-222, and miR-10 in PDCA cells, promoting an almost complete abolishment of microRNA expression. Silencing of these microRNAs resulted in a significant increase in the levels of their targets. Moreover, the combination of microRNA silencing, namely miR-21, with low amounts of the chemotherapeutic drug sunitinib resulted in a strong and synergistic antitumor effect, showing that this combined strategy could be of great importance for therapeutic application in PDAC. Keywords: pancreatic cancer gene therapy, anti-microRNAs oligonucleotides, delivery nanosystems, albumin-associated lipoplexes

  11. Predicting response to preoperative chemotherapy agents by identifying drug action on modeled microRNA regulation networks.

    Directory of Open Access Journals (Sweden)

    Lida Zhu

    Full Text Available Identifying patients most responsive to specific chemotherapy agents in neoadjuvant settings can help to maximize the benefits of treatment and minimize unnecessary side effects. Metagene approaches that predict response based on gene expression signatures derived from an associative analysis of clinical data can identify chance associations caused by the heterogeneity of a tumor, leading to reproducibility issues in independent validations. In this study, to incorporate information from drug mechanisms of action, we explore the potential of microRNA regulation networks as a new feature space for identifying predictive markers. We introduce a measure we term the CoMi (Context-specific-miRNA-regulation pattern to represent a descriptive feature of the miRNA regulation network in the transcriptome. We examine whether the modifications to the CoMi pattern on specific biological processes are a useful representation of drug action by predicting the response to neoadjuvant Paclitaxel treatment in breast cancer and show that the drug counteracts the CoMi network dysregulation induced by tumorigenesis. We then generate a quantitative testbed to investigate the ability of the CoMi pattern to distinguish FDA approved breast cancer drugs from other FDA approved drugs not related to breast cancer. We also compare the ability of the CoMi and metagene methods to predict response to neoadjuvant Paclitaxel treatment in clinical cohorts. We find the CoMi method outperforms the metagene method, achieving area under curve (AUC values of 0.78 and 0.66 respectively. Furthermore, several of the predicted CoMi features highlight the network-based mechanism of drug resistance. Thus, our study suggests that explicitly modeling the drug action using network biology provides a promising approach for predictive marker discovery.

  12. MicroRNA in carcinogenesis & cancer diagnostics: A new paradigm

    OpenAIRE

    Ahmad, Javed; Seyed E Hasnain; Siddiqui, Maqsood A; Ahamed, Maqusood; Musarrat, Javed; Al-Khedhairy, Abdulaziz A.

    2013-01-01

    MicroRNAs (miRNAs) are small 22-25 nucleotides long non-coding RNAs, that are conserved during evolution, and control gene expression in metazoan animals, plants, viruses, and bacteria primarily at post-transcriptional and transcriptional levels. MiRNAs ultimately regulate target gene expression by degrading the corresponding mRNA and/or inhibiting their translation. Currently, the critical functions of miRNAs have been established in regulating immune system, cell proliferation, differentiat...

  13. MicroRNA expression profile in head and neck cancer: HOX-cluster embedded microRNA-196a and microRNA-10b dysregulation implicated in cell proliferation

    International Nuclear Information System (INIS)

    Current evidence implicates aberrant microRNA expression patterns in human malignancies; measurement of microRNA expression may have diagnostic and prognostic applications. Roles for microRNAs in head and neck squamous cell carcinomas (HNSCC) are largely unknown. HNSCC, a smoking-related cancer, is one of the most common malignancies worldwide but reliable diagnostic and prognostic markers have not been discovered so far. Some studies have evaluated the potential use of microRNA as biomarkers with clinical application in HNSCC. MicroRNA expression profile of oral squamous cell carcinoma samples was determined by means of DNA microarrays. We also performed gain-of-function assays for two differentially expressed microRNA using two squamous cell carcinoma cell lines and normal oral keratinocytes. The effect of the over-expression of these molecules was evaluated by means of global gene expression profiling and cell proliferation assessment. Altered microRNA expression was detected for a total of 72 microRNAs. Among these we found well studied molecules, such as the miR-17-92 cluster, comprising potent oncogenic microRNA, and miR-34, recently found to interact with p53. HOX-cluster embedded miR-196a/b and miR-10b were up- and down-regulated, respectively, in tumor samples. Since validated HOX gene targets for these microRNAs are not consistently deregulated in HNSCC, we performed gain-of-function experiments, in an attempt to outline their possible role. Our results suggest that both molecules interfere in cell proliferation through distinct processes, possibly targeting a small set of genes involved in cell cycle progression. Functional data on miRNAs in HNSCC is still scarce. Our data corroborate current literature and brings new insights into the role of microRNAs in HNSCC. We also show that miR-196a and miR-10b, not previously associated with HNSCC, may play an oncogenic role in this disease through the deregulation of cell proliferation. The study of microRNA

  14. Unraveling the mystery of cancer by secretory microRNA: Horizontal microRNA transfer between living cells

    Directory of Open Access Journals (Sweden)

    Nobuyoshi eKosaka

    2012-01-01

    Full Text Available microRNAs (miRNAs have been identified as a fine-tuner in a wide array of biological processes, including development, organogenesis, metabolism, and homeostasis. Deregulation of miRNA leads to the disease status, especially cancer. This occurs through a variety of mechanisms, such as genetic alterations, epigenetic regulation, or altered expression of transcription factors, which target miRNAs. Recently, it was discovered that extracellular miRNAs circulate in the blood of both healthy and diseased patients. Most of the circulating miRNAs are included in RNA-binding proteins, apoptotic bodies, microvesicles, and exosomes. However, the secretory mechanism and biological function, as well as the meaning of the existence of extracellular miRNAs, remain largely unclear. In this article, we summarize the latest and most significant discoveries of original research on secretory miRNA involvement in many aspects of physiological and pathological conditions, with a special focus on cancer. In addition, we discuss a new aspect of cancer research that is revealed by the emergence of secretory miRNA.

  15. Arm Selection Preference of MicroRNA-193a Varies in Breast Cancer

    OpenAIRE

    Kuo-Wang Tsai; Chung-Man Leung; Yi-Hao Lo; Ting-Wen Chen; Wen-Ching Chan; Shou-Yu Yu; Ya-Ting Tu; Hing-Chung Lam; Sung-Chou Li; Luo-Ping Ger; Wen-Shan Liu; Hong-Tai Chang

    2016-01-01

    MicroRNAs (miRNAs) are short noncoding RNAs derived from the 3′ and 5′ ends of the same precursor. However, the biological function and mechanism of miRNA arm expression preference remain unclear in breast cancer. We found significant decreases in the expression levels of miR-193a-5p but no significant differences in those of miR-193a-3p in breast cancer. MiR-193a-3p suppressed breast cancer cell growth and migration and invasion abilities, whereas miR-193a-5p suppressed cell growth but did n...

  16. MicroRNA-18a as a promising biomarker for cancer detection: a meta-analysis

    OpenAIRE

    Jin, Shan; Tan, Shi-Sheng; Li, Hang

    2015-01-01

    Patients with cancer discovered at an early stage have relatively high survival rates. Increasing researches have shown the potential of detecting dysregulated microRNA-18a (miR-18a) to diagnose cancer. However, non-uniform results in previous studies were found. Thus, this meta-analysis was conducted to further explore the clinical applicability of miR-18a as an ideal biomarker for cancer detection. Suitable articles were obtained from online databases like PubMed, Embase, Cochrane, CBM and ...

  17. Role of microRNAs in cancers of the female reproductive tract: insights from recent clinical and experimental discovery studies.

    Science.gov (United States)

    Logan, Monica; Hawkins, Shannon M

    2015-02-01

    microRNAs (miRNAs) are small RNA molecules that represent the top of the pyramid of many tumorigenesis cascade pathways as they have the ability to affect multiple, intricate, and still undiscovered downstream targets. Understanding how miRNA molecules serve as master regulators in these important networks involved in cancer initiation and progression open up significant innovative areas for therapy and diagnosis that have been sadly lacking for deadly female reproductive tract cancers. This review will highlight the recent advances in the field of miRNAs in epithelial ovarian cancer, endometrioid endometrial cancer and squamous-cell cervical carcinoma focusing on studies associated with actual clinical information in humans. Importantly, recent miRNA profiling studies have included well-characterized clinical specimens of female reproductive tract cancers, allowing for studies correlating miRNA expression with clinical outcomes. This review will summarize the current thoughts on the role of miRNA processing in unique miRNA species present in these cancers. In addition, this review will focus on current data regarding miRNA molecules as unique biomarkers associated with clinically significant outcomes such as overall survival and chemotherapy resistance. We will also discuss why specific miRNA molecules are not recapitulated across multiple studies of the same cancer type. Although the mechanistic contributions of miRNA molecules to these clinical phenomena have been confirmed using in vitro and pre-clinical mouse model systems, these studies are truly only the beginning of our understanding of the roles miRNAs play in cancers of the female reproductive tract. This review will also highlight useful areas for future research regarding miRNAs as therapeutic targets in cancers of the female reproductive tract. PMID:25294164

  18. The role of microRNAs in human liver cancers.

    Science.gov (United States)

    Braconi, Chiara; Henry, Jon C; Kogure, Takayuki; Schmittgen, Thomas; Patel, Tushar

    2011-12-01

    Hepatocellular carcinoma (HCC) is a primary malignancy of the liver of global importance. Recent studies of the expression and role of microRNA (miRNA) in HCC are providing new insights into disease pathogenesis. In addition, therapeutic efforts targeting specific miRNAs are being evaluated in animal models of HCC. The potential of miRNAs as biomarkers of disease or prognostic markers is being explored. Herein, we review studies of miRNA expression in human HCC, and discuss recent advances in knowledge about the involvement and role of selected miRNAs in disease pathogenesis, as biomarkers, or as therapeutic targets for HCC. PMID:22082761

  19. Urine microRNAs as biomarkers for bladder cancer: a diagnostic meta-analysis

    OpenAIRE

    Cheng Y; Deng X; Yang X; Zhang X; Li P; Tao J; Lu Q; Wang Z

    2015-01-01

    Yidong Cheng,* Xiaheng Deng,* Xiao Yang,* Pengchao Li, Xiaolei Zhang, Peng Li, Jun Tao, Qiang Lu, Zengjun Wang Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, People’s Republic of China *These authors contributed equally to this work Background: The diagnostic value of microRNA (miRNA) detection in patients with bladder cancer (BCa) is controversial. We performed a diagnostic meta-analysis to evaluate current evidence on the use of mi...

  20. Human cancer cell line microRNAs associated with in vitro sensitivity to paclitaxel

    OpenAIRE

    Chen, Ning; CHON, HYE SOOK; Xiong, Yin; MARCHION, Douglas C.; Judson, Patricia L.; Hakam, Ardeshir; Gonzalez-Bosquet, Jesus; Permuth-Wey, Jennifer; WENHAM, ROBERT M.; Apte, Sachin M.; Cheng, Jin Q.; Sellers, Thomas A.; Lancaster, Johnathan M.

    2013-01-01

    Paclitaxel is a mainstay of treatment for many solid tumors, and frequently, clinical outcome is influenced by paclitaxel sensitivity. Despite this, our understanding of the molecular basis of paclitaxel response is incomplete. Recently, it has been shown that microRNAs (miRNAs) influence messenger RNA (mRNA) transcriptional control and can contribute to human carcinogenesis. In the present study, our objective was to identify miRNAs associated with cancer cell line response to paclitaxel and...

  1. MicroRNA-145 targets YES and STAT1 in colon cancer cells

    DEFF Research Database (Denmark)

    Gregersen, Lea H; Jacobsen, Anders B; Frankel, Lisa; Wen, Jiayu; Krogh, Anders; Lund, Anders H.

    2010-01-01

    miRNA overexpression. Gene Ontology analysis showed an overrepresentation of genes involved in cell death, cellular growth and proliferation, cell cycle, gene expression and cancer. A number of the identified miRNA targets have previously been implicated in cancer, including YES, FSCN1, ADAM17, BIRC2......, VANGL1 as well as the transcription factor STAT1. Both YES and STAT1 were verified as direct miR-145 targets. CONCLUSIONS/SIGNIFICANCE: The study identifies and validates new cancer-relevant direct targets of miR-145 in colon cancer cells and hereby adds important mechanistic understanding of the tumor......BACKGROUND: MicroRNAs (miRNAs) have emerged as important gene regulators and are recognized as key players in tumorigenesis. miR-145 is reported to be down-regulated in several cancers, but knowledge of its targets in colon cancer remains limited. METHODOLOGY/PRINCIPAL FINDINGS: To investigate the...

  2. Profiling analysis of circulating microRNA expression in cervical cancer

    Science.gov (United States)

    NAGAMITSU, YUZO; NISHI, HIROTAKA; SASAKI, TORU; TAKAESU, YOTARO; TERAUCHI, FUMITOSHI; ISAKA, KEIICHI

    2016-01-01

    MicroRNA (miRNA) expression is altered in cancer cells and is associated with the development and progression of various types of cancer. Accordingly, miRNAs may serve as diagnostic or prognostic biomarkers in cancer patients. In this study, we attempted to analyze circulating exosomal miRNA in patients with cervical cancer. Total RNA was extracted from the serum of healthy subjects, subjects with cervical intraepithelial neoplasia (CIN) and patients with cervical cancer. We first investigated miRNA expression profiles in 6 serum samples from healthy subjects and patients with cervical cancer using the miRCURY LNA microRNA array. miRNAs with significant differences in expression were validated in a larger sample set by quantitative reverse transcription-polymerase chain reaction, using TaqMan gene expression assays. The results of the miRCURY LNA microRNA array indicated that 6 of 1,223 miRNAs found in serum samples from cervical cancer patients and normal controls exhibited a >3.0-fold change in expression level in subjects with cervical cancer, with a P-value of <0.01. In a validation set (n=131) that investigated the expression of 4 of the 6 miRNAs (miR-483-5p, miR-1246, miR-1275 and miR-1290), miR-1290 was found to have significantly higher expression levels in cervical cancer samples (n=45) compared with control samples (n=31). We also found that the median levels of these miRNAs were significantly higher in subjects with cervical cancer (n=45) compared with those in subjects with CIN (n=55). Circulating miRNAs were not correlated with clinicopathological parameters. However, receiver operating characteristic curve analysis suggested that these serum miRNAs may be useful diagnostic markers in cervical cancer. The expression of circulating miR-1290 was significantly higher in the blood of cervical cancer patients compared with that in controls and may thus serve as a useful biomarker in cervical cancer diagnosis. However, larger studies are required to fully

  3. microRNAs and cancer metabolism reprogramming: the paradigm of metformin.

    Science.gov (United States)

    Pulito, Claudio; Donzelli, Sara; Muti, Paola; Puzzo, Luisa; Strano, Sabrina; Blandino, Giovanni

    2014-06-01

    Increasing evidence witnesses that cancer metabolism alterations represent a critical hallmark for many types of human tumors. There is a strong need to understand and dissect the molecular mechanisms underlying cancer metabolism to envisage specific biomarkers and underpin critical molecular components that might represent novel therapeutic targets. One challenge, that is the focus of this review, is the reprogramming of the altered metabolism of a cancer cell toward that of un-transformed cell. The anti-hyperglicemic agent, metformin has proven to be effective in reprogramming the metabolism of cancer cells even from those subpopulations endowed with cancer stem like features and very high chemoresistenace to conventional anticancer treatments. A functional interplay involving selective modulation of microRNAs (miRNAs) takes place along the anticancer metabolic effects exerted by metformin. The implications of this interplay will be also discussed in this review. PMID:25333033

  4. Single-nucleotide polymorphisms among microRNA: big effects on cancer

    Institute of Scientific and Technical Information of China (English)

    Feng-Ju Song; Ke-Xin Chen

    2011-01-01

    MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression at the transcriptional or posttranscriptional level. Many miRNAs are found to play a significant role in cancer development either as tumor suppressor genes or as oncogenes. Examination of tumor-specific miRNA expression profiles in diverse cancers has revealed widespread deregulation of these molecules, whose loss and overexpression respectively have diagnostic and prognostic significance. Genetic variations, mostly single-nucleotide polymorphisms (SNPs) within miRNA sequences or their target sites, have been found to be associated with many kinds of cancers. In this review, we summarize the current knowledge of miRNAs including their biogenesis and role in cancer development, and finally, how SNPs among miRNAs affect miRNA biogenesis and contribute to cancer.

  5. The roles and clinical significance of microRNAs in cervical cancer.

    Science.gov (United States)

    Wang, Fenfen; Li, Baohua; Xie, Xing

    2016-02-01

    Cervical carcinogenesis induced by persistent human papillomavirus (HPV) infection represents a stepwise progression from precursors to invasive cervical cancer. Accumulated evidence has shown aberrant expression of microRNAs (miRNAs) in cervical cancer tissues and cells. Further studies reveal that miRNAs play key roles in the initiation and progression of cervical cancer, via specific signaling pathways, including E6-p53, E7-pRb, phosphoinositide-3 kinase (PI3K)-Akt, Notch, Wnt/β-catenin, and Hedgehog pathways. Some studies demonstrate that miRNAs might serve as biomarkers or therapeutic targets, presenting a potential prospect in clinical practice. All results provide new insights into the function of miRNAs and the pathogenesis of cervical cancer induced by viral oncoproteins. New approaches for miRNA-based prevention and management for cervical cancer will be developed in the future. PMID:26356641

  6. A study on the overexpression of microRNAs and lung cancer

    Institute of Scientific and Technical Information of China (English)

    Longfeng Xu; Zhiping Wu; Yan Chen; Rui Feng; Chun Hou; Fan Yang; Qishun Zhu

    2013-01-01

    MicroRNAs (miRNAs), which contains approximately 22 nt, belong to a smal endogenous, non-coding regulatory single-stranded RNA molecules. They are posttranscriptional regulators of gene expression and highly conserved in evolution. Many researches show that miRNAs involved in many processes, including tumor formation, cel proliferation and apoptosis and proliferation and metastasis of cancer cel s. Among that, the relationship between miRNAs and lung cancer is one of the most focal areas for the researchers, because the abnormal expressions of miRNAs were significantly associated with the occurrence and development of lung cancer. The expression level of dif erent miRNAs in lung cancer cel s exist dif erences, compared with normal lung tissue cel s, there are two classes of expression:over-expression level and low expression level. In this review, we focused on studying the mechanism of overexpression miRNAs in lung cancer.

  7. Prognostic Value of MicroRNA-182 in Cancers: A Meta-Analysis

    OpenAIRE

    2015-01-01

    Objective. MicroRNA-182 (miR-182) exhibits altered expression in various cancers. The aim of this study was to investigate the predictive value of miR-182 expression for cancer patient survival. Methods. Eligible studies were identified through multiple search strategies, and the hazard ratios (HRs) for patient outcomes were extracted and estimated. A meta-analysis was performed to evaluate the prognostic value of miR-182. Results. In total, 14 studies were included. A high miR-182 expression...

  8. Differential microRNA expression signatures and cell type-specific association with Taxol resistance in ovarian cancer cells

    Directory of Open Access Journals (Sweden)

    Kim YW

    2014-02-01

    downregulation of the two miRNAs was associated with better survival, perhaps increasing the sensitivity of cancer cells to Taxol. In the chemo-sensitive patient group, only miR-647 could be a prognosis marker. These miRNAs inhibit several interacting genes of p53 networks, especially in TUOS-3 and TUOS-4, and showed cell line-specific inhibition effects. Taken together, the data indicate that the three miRNAs are closely associated with Taxol resistance and potentially better prognosis factors. Our results suggest that these miRNAs were successfully and reliably identified and would be used in the development of miRNA therapies in treating ovarian cancer. Keywords: microRNA, ovarian cancer, Taxol resistance, Kaplan–Meier survival analysis

  9. BRCA1 and MicroRNAs: Emerging Networks and Potential Therapeutic Targets

    OpenAIRE

    Chang, Suhwan; Sharan, Shyam K.

    2012-01-01

    BRCA1 is a well-known tumor suppressor implicated in familial breast and ovarian cancer. Since its cloning in 1994, numerous studies have established BRCA1’s role in diverse cellular and biochemical processes, such as DNA damage repair, cell cycle control, and transcriptional regulation as well as ubiquitination. In addition, a number of recent studies have functionally linked this tumor suppressor to another important cellular regulator, microRNAs, which are short (19–22 nt) RNAs that were d...

  10. The application of microRNAs in cancer diagnostics

    DEFF Research Database (Denmark)

    Sørensen, Karina Dalsgaard; Ostenfeld, Marie Stampe; Kristensen, Helle;

    2012-01-01

    identified exosome-associated tumor-derived miRNAs in, e.g., blood samples from cancer patients, suggesting that miRNAs may be useful as circulation biomarkers for noninvasive diagnostic testing. In this chapter, we review the current state of development of miRNAs as cancer biomarkers with examples from......MicroRNAs (miRNAs) play important biological roles in cancer development and progression. During the past decade, widespread use of novel high-throughput technologies for miRNA profiling (e.g., microarrays and next-generation sequencing) has revealed deregulation of miRNA expression as a common...... hallmark of human cancer. Furthermore, miRNAs have been found to be a new class of promising cancer biomarkers with potential to improve the accuracy of diagnosis and prognosis in several hematologic and solid malignancies, as well as to predict response to specific treatments. Recent studies have...

  11. Research Progress of MicroRNA in Early Detection of Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    Ze-Hua Wang

    2015-01-01

    Full Text Available Objective: This review aimed to update the progress of microRNA (miRNA in early detection of ovarian cancer. We discussed the current clinical diagnosis methods and biomarkers of ovarian cancer, especially the methods of miRNA in early detection of ovarian cancer. Data Sources: We collected all relevant studies about miRNA and ovarian cancer in PubMed and CNKI from 1995 to 2015. Study Selection: We included all relevant studies concerning miRNA in early detection of ovarian cancer, and excluded the duplicated articles. Results: miRNAs play a key role in various biological processes of ovarian cancer, such as development, proliferation, differentiation, apoptosis and metastasis, and these phenomena appear in the early-stage. Therefore, miRNA can be used as a new biomarker for early diagnosis of ovarian cancer, intervention on miRNA expression of known target genes, and potential target genes can achieve the effect of early prevention. With the development of nanoscience and technology, analysis methods of miRNA are also quickly developed, which may provide better characterization of early detection of ovarian cancer. Conclusions: In the near future, miRNA therapy could be a powerful tool for ovarian cancer prevention and treatment, and combining with the new analysis technology and new nanomaterials, point-of-care tests for miRNA with high throughput, high sensitivity, and strong specificity are developed to achieve the application of diagnostic kits in screening of early ovarian cancer.

  12. MicroRNAs: Modulators of the Ras Oncogenes in Oral Cancer.

    Science.gov (United States)

    Murugan, Avaniyapuram Kannan; Munirajan, Arasambattu Kannan; Alzahrani, Ali S

    2016-07-01

    Oral squamous cell carcinoma (OSCC) of the head and neck is one of the six most common cancers in the world. OSCC remains the most common cause of cancer deaths in Asian countries. Conventional treatments for OSCC have not improved the overall 5 years survival and therefore alternative therapeutic targets are often sought. Ras is one of the most frequently deregulated oncogenes in oral cancer. Direct targeting the ras has proven unrealistic and hence, exploring and understanding alternative pathways and/or molecules which regulate ras and its signaling that could pave the way for novel molecular targets and therapy for oral cancer. Recently, microRNAs (miRNAs) have been reported to regulate ras oncogenes in human cancers. In this article, we address the microRNA-mediated regulation of the ras oncogenes in oral cancer. We describe extensively the tumor suppressive and oncogenic roles of miRNAs in regulation of ras oncogenes in OSCC. We also discuss the role of miRNA-mediated ras regulation in therapeutic determination of oral cancer. Complete understanding of the miRNA regulation of ras oncogenes in oral cancer may facilitate to plan better strategies for diagnosis, molecular therapeutic targeting and the overall prognosis of this common and deadly cancer. J. Cell. Physiol. 231: 1424-1431, 2016. © 2015 Wiley Periodicals, Inc. PMID:26620726

  13. Emerging Evidence for MicroRNAs as Regulators of Cancer Stem Cells

    International Nuclear Information System (INIS)

    Cancer stem cells are defined as a subpopulation of cells within a tumor that are capable of self-renewal and differentiation into the heterogeneous cell lineages that comprise the tumor. Many studies indicate that cancer stem cells may be responsible for treatment failure and relapse in cancer patients. The factors that regulate cancer stem cells are not well defined. MicroRNAs (miRNAs) are small non-coding RNAs that regulate translational repression and transcript degradation. miRNAs play a critical role in embryonic and inducible pluripotent stem cell regulation and emerging evidence supports their role in cancer stem cell evolution. To date, miRNAs have been shown to act either as tumor suppressor genes or oncogenes in driving critical gene expression pathways in cancer stem cells in a wide range of human malignancies, including hematopoietic and epithelial tumors and sarcomas. miRNAs involved in cancer stem cell regulation provide attractive, novel therapeutic targets for cancer treatment. This review attempts to summarize progress to date in defining the role of miRNAs in cancer stem cells

  14. The effects of MicroRNA transfections on global patterns of gene expression in ovarian cancer cells are functionally coordinated

    Directory of Open Access Journals (Sweden)

    Shahab Shubin W

    2012-08-01

    Full Text Available Abstract Background MicroRNAs (miRNAs are a class of small RNAs that have been linked to a number of diseases including cancer. The potential application of miRNAs in the diagnostics and therapeutics of ovarian and other cancers is an area of intense interest. A current challenge is the inability to accurately predict the functional consequences of exogenous modulations in the levels of potentially therapeutic miRNAs. Methods In an initial effort to systematically address this issue, we conducted miRNA transfection experiments using two miRNAs (miR-7, miR-128. We monitored the consequent changes in global patterns of gene expression by microarray and quantitative (real-time polymerase chain reaction. Network analysis of the expression data was used to predict the consequence of each transfection on cellular function and these predictions were experimentally tested. Results While ~20% of the changes in expression patterns of hundreds to thousands of genes could be attributed to direct miRNA-mRNA interactions, the majority of the changes are indirect, involving the downstream consequences of miRNA-mediated changes in regulatory gene expression. The changes in gene expression induced by individual miRNAs are functionally coordinated but distinct between the two miRNAs. MiR-7 transfection into ovarian cancer cells induces changes in cell adhesion and other developmental networks previously associated with epithelial-mesenchymal transitions (EMT and other processes linked with metastasis. In contrast, miR-128 transfection induces changes in cell cycle control and other processes commonly linked with cellular replication. Conclusions The functionally coordinated patterns of gene expression displayed by different families of miRNAs have the potential to provide clinicians with a strategy to treat cancers from a systems rather than a single gene perspective.

  15. MicroRNA-148a inhibits breast cancer migration and invasion by directly targeting WNT-1.

    Science.gov (United States)

    Jiang, Qian; He, Miao; Ma, Meng-Tao; Wu, Hui-Zhe; Yu, Zhao-Jin; Guan, Shu; Jiang, Long-Yang; Wang, Yan; Zheng, Da-Di; Jin, Feng; Wei, Min-Jie

    2016-03-01

    Wnt/β-catenin signaling pathway influences embryonic development, cell polarity and adhesion, apoptosis and tumorigenesis. MicroRNAs (miRNAs) function as important regulators of the tumorigenesis and metastasis. In the present study, we aimed to find novel targets and mechanisms of microRNA-148a (miR-148a) in regulating the migration and invasion of breast cancer cells. In the present study, miR-148a was found downregulated in human breast cancer tissues and cell lines. The ectopic miR-148a expression inhibited the migration and invasion of MCF-7 and MDA-MB-231 breast cancer cells. Furthermore, we demonstrated that WNT-1, one of the ligands of Wnt/β-catenin signaling pathway, was a direct target of miR-148a. The overexpression of miR-148a reduced the mRNA and protein expression levels of WNT-1, also decreased the expression levels of the key components of Wnt/β-catenin pathway, including β-catenin, metalloproteinase-7 (MMP-7) and T-cell factor-4 (TCF-4) in MCF-7 and MDA-MB-231 cells. In addition, the data showed that the expression of WNT-1 was significantly higher in human breast cancer tissues compared with the adjacent normal tissues and the expression of miR-148a was negatively correlated with the WNT-1 expression in human breast cancer tissues. Taken together, our results suggest that miR-148a can suppress the migration and invasion of breast cancer cells by targeting WNT-1 and inhibiting Wnt/β-catenin signaling pathway and this will provide new insights into the molecular mechanisms of breast cancer metastasis. PMID:26707142

  16. Identifying Network Perturbation in Cancer

    Science.gov (United States)

    Logsdon, Benjamin A.; Gentles, Andrew J.; Lee, Su-In

    2016-01-01

    We present a computational framework, called DISCERN (DIfferential SparsE Regulatory Network), to identify informative topological changes in gene-regulator dependence networks inferred on the basis of mRNA expression datasets within distinct biological states. DISCERN takes two expression datasets as input: an expression dataset of diseased tissues from patients with a disease of interest and another expression dataset from matching normal tissues. DISCERN estimates the extent to which each gene is perturbed—having distinct regulator connectivity in the inferred gene-regulator dependencies between the disease and normal conditions. This approach has distinct advantages over existing methods. First, DISCERN infers conditional dependencies between candidate regulators and genes, where conditional dependence relationships discriminate the evidence for direct interactions from indirect interactions more precisely than pairwise correlation. Second, DISCERN uses a new likelihood-based scoring function to alleviate concerns about accuracy of the specific edges inferred in a particular network. DISCERN identifies perturbed genes more accurately in synthetic data than existing methods to identify perturbed genes between distinct states. In expression datasets from patients with acute myeloid leukemia (AML), breast cancer and lung cancer, genes with high DISCERN scores in each cancer are enriched for known tumor drivers, genes associated with the biological processes known to be important in the disease, and genes associated with patient prognosis, in the respective cancer. Finally, we show that DISCERN can uncover potential mechanisms underlying network perturbation by explaining observed epigenomic activity patterns in cancer and normal tissue types more accurately than alternative methods, based on the available epigenomic data from the ENCODE project. PMID:27145341

  17. PPARs in Liver Diseases and Cancer: Epigenetic Regulation by MicroRNAs

    Directory of Open Access Journals (Sweden)

    Marion Peyrou

    2012-01-01

    Full Text Available Peroxisome-proliferator-activated receptors (PPARs are ligand-activated nuclear receptors that exert in the liver a transcriptional activity regulating a whole spectrum of physiological functions, including cholesterol and bile acid homeostasis, lipid/glucose metabolism, inflammatory responses, regenerative mechanisms, and cell differentiation/proliferation. Dysregulations of the expression, or activity, of specific PPAR isoforms in the liver are therefore believed to represent critical mechanisms contributing to the development of hepatic metabolic diseases, disorders induced by hepatic viral infections, and hepatocellular adenoma and carcinoma. In this regard, specific PPAR agonists have proven to be useful to treat these metabolic diseases, but for cancer therapies, the use of PPAR agonists is still debated. Interestingly, in addition to previously described mechanisms regulating PPARs expression and activity, microRNAs are emerging as new important regulators of PPAR expression and activity in pathophysiological conditions and therefore may represent future therapeutic targets to treat hepatic metabolic disorders and cancers. Here, we reviewed the current knowledge about the general roles of the different PPAR isoforms in common chronic metabolic and infectious liver diseases, as well as in the development of hepatic cancers. Recent works highlighting the regulation of PPARs by microRNAs in both physiological and pathological situations with a focus on the liver are also discussed.

  18. MicroRNA profiling of gastric cancer patients from formalin-fixed paraffin-embedded samples

    OpenAIRE

    OSAWA, SOSHI; Shimada, Yutaka; Sekine, Shinichi; Okumura, Tomoyuki; NAGATA, TAKUYA; Fukuoka, Junya; Tsukada, Kazuhiro

    2011-01-01

    MicroRNA (miRNA) is a small non-coding RNA that targets specific mRNA. Recent progress in the extraction of RNA from formalin-fixed paraffin-embedded (FFPE) tissues has facilitated miRNA profiling using samples stored in laboratories worldwide. In the present study, miRNA profiling of gastric cancer patients is determined using FFPE samples. First, criteria were established for determining evaluable RNA from the FFPE samples. miRNA profiling was then undertaken using miRNA oligo chips with 88...

  19. A microRNA DNA methylation signature for human cancer metastasis

    OpenAIRE

    Lujambio, Amaia; Calin, George A; Villanueva, Alberto; Ropero, Santiago; Sánchez-Céspedes, Montserrat; Blanco, David; Montuenga, Luis M.; Rossi, Simona; Nicoloso, Milena S.; Faller, William J.; Gallagher, William M.; Eccles, Suzanne A; Croce, Carlo M.; Esteller, Manel

    2008-01-01

    MicroRNAs (miRNAs) are small, noncoding RNAs that can contribute to cancer development and progression by acting as oncogenes or tumor suppressor genes. Recent studies have also linked different sets of miRNAs to metastasis through either the promotion or suppression of this malignant process. Interestingly, epigenetic silencing of miRNAs with tumor suppressor features by CpG island hypermethylation is also emerging as a common hallmark of human tumors. Thus, we wondered whether there was a m...

  20. MicroRNAs as putative mediators of treatment response in prostate cancer.

    LENUS (Irish Health Repository)

    O'Kelly, Fardod

    2012-05-22

    MicroRNAs (miRNAs) are an abundant class of noncoding RNAs that function to regulate post-transcriptional gene expression, predominantly by translational repression. In addition to their role in prostate cancer initiation and progression, recent evidence suggests that miRNAs might also participate in treatment response across a range of therapies including radiation treatment, chemotherapy and androgen suppression. The mechanism of this regulation is thought to be multifactorial and is currently poorly understood. To date, only a small number of studies have examined the functional role of miRNAs in response to prostate cancer treatment. Elucidating the role of miRNAs in treatment response following radiotherapy, chemotherapy and androgen suppression will provide new avenues of investigation for the development of novel therapies for the treatment of prostate cancer.

  1. Recent Advance in Biosensors for microRNAs Detection in Cancer

    International Nuclear Information System (INIS)

    MicroRNAs (miRNAs) are short non-protein-coding RNA molecules that regulate the expression of a wide variety of genes. They act by sequence-specific base pairing in the 3′ untranslated region (3′UTR) of the target mRNA leading to mRNA degradation or translation inhibition. Recent studies have implicated miRNAs in a wide range of biological processes and diseases including development, metabolism and cancer, and revealed that expression levels of individual miRNAs may serve as reliable molecular biomarkers for cancer diagnosis and prognosis. Therefore, a major challenge is to develop innovative tools able to couple high sensitivity and specificity for rapid detection of miRNAs in a given cell or tissue. In this review, we focus on the latest innovative approaches proposed for miRNA profiling in cancer and discuss their advantages and disadvantages

  2. Cell-free microRNAs in blood and other body fluids, as cancer biomarkers.

    Science.gov (United States)

    Ortiz-Quintero, Blanca

    2016-06-01

    The discovery of cell-free microRNAs (miRNAs) in serum, plasma and other body fluids has yielded an invaluable potential source of non-invasive biomarkers for cancer and other non-malignant diseases. miRNAs in the blood and other body fluids are highly stable in biological samples and are resistant to environmental conditions, such as freezing, thawing or enzymatic degradation, which makes them convenient as potential biomarkers. In addition, they are more easily sampled than tissue miRNAs. Altered levels of cell-free miRNAs have been found in every type of cancer analysed, and increasing evidence indicates that they may participate in carcinogenesis by acting as cell-to-cell signalling molecules. This review summarizes the biological characteristics and mechanisms of release of cell-free miRNAs that make them promising candidates as non-invasive biomarkers of cancer. PMID:27218664

  3. Implications of microRNAs in Colorectal Cancer Development, Diagnosis, Prognosis and Therapeutics

    Directory of Open Access Journals (Sweden)

    Haiyan eZhai

    2011-11-01

    Full Text Available MicroRNAs (miRNAs are a class of non-coding small RNAs with critical regulatory functions as post-transcriptional regulators. Due to the fundamental importance and broad impact of miRNAs on multiple genes and pathways, dysregulated miRNAs have been associated with human diseases, including cancer. Colorectal cancer (CRC is among the most deadly diseases, and miRNAs offer a new frontier for target discovery and novel biomarkers for both diagnosis and prognosis. In this review, we summarize the recent advancement of miRNA research in CRC, in particular, the roles of miRNAs in colorectal cancer stem cells, EMT, chemoresistance, therapeutics, diagnosis and prognosis.

  4. MicroRNAs transported by exosomes in body fluids as mediators of intercellular communication in cancer

    Directory of Open Access Journals (Sweden)

    Salido-Guadarrama I

    2014-07-01

    Full Text Available Iván Salido-Guadarrama,1 Sandra Romero-Cordoba,1 Oscar Peralta-Zaragoza,2 Alfredo Hidalgo-Miranda,1 Mauricio Rodríguez-Dorantes1 1Oncogenomics Laboratory, National Institute of Genomics Medicine, Mexico City, Mexico; 2Direction of Chronic Infections and Cancer, Research Center in Infectious Diseases, National Institute of Public Health, Cuernavaca, Morelos, Mexico Abstract: Cancer-cell communication is an important and complex process, achieved through a diversity of mechanisms that allows tumor cells to mold and influence their environment. In recent years, evidence has accumulated indicating that cells communicate via the release and delivery of microRNAs (miRNAs packed into tumor-released (TR exosomes. Understanding the role and mode of action of miRNAs from TR exosomes is of paramount importance in the field of cancer biomarker discovery and for the development of new biomedical applications for cancer therapeutics. In this review, we focus on miRNAs secreted via TR exosomes, which by acting in a paracrine or endocrine manner, facilitate a diversity of signaling mechanisms between cancer cells. We address their contribution as signaling molecules, to the establishment, maintenance, and enhancement of the tumor microenvironment and the metastatic niche in cancer. Finally, we address the potential role of these molecules as biomarkers in cancer diagnosis and prognosis and their impact as a biomedical tool in cancer therapeutics. Keywords: tumor cells, multivesicular bodies, interference RNA, biomarkers and therapeutics

  5. The Impact of Extracellular Vesicle-Encapsulated Circulating MicroRNAs in Lung Cancer Research

    Directory of Open Access Journals (Sweden)

    Yu Fujita

    2014-01-01

    Full Text Available Lung cancer is the leading cause of cancer-related deaths. Biomarkers for lung cancer have raised great expectations in their clinical applications for early diagnosis, survival, and therapeutic responses. MicroRNAs (miRNAs, a family of short endogenous noncoding RNAs, play critical roles in cell growth, differentiation, and the development of various types of cancers. Current studies have shown that miRNAs are present in the extracellular spaces, packaged into various membrane-bound vesicles. Tumor-specific circulating miRNAs have been developed as early diagnostic biomarkers for lung cancer. Remarkably, some studies have succeeded in discovering circulating miRNAs with prognostic or predictive significance. Extracellular vesicles (EVs, such as exosomes and microvesicles, are recognized as novel tools for cell-cell communication and as biomarkers for various diseases. Their vesicle composition and miRNA content have the ability to transfer biological information to recipient cells and play an important role in cancer metastasis and prognosis. This review provides an in-depth summary of current findings on circulating miRNAs in lung cancer patients used as diagnostic biomarkers. We also discuss the role of EV miRNAs in cell-cell communication and explore the effectiveness of these contents as predictive biomarkers for cancer malignancy.

  6. Circulating microRNAs as minimally invasive biomarkers for cancer theragnosis and prognosis

    Directory of Open Access Journals (Sweden)

    William C. S. Cho

    2011-02-01

    Full Text Available Novel cancer biomarker discovery is urgently needed for cancer theragnosis and prognosis, and among the many possible types of samples, blood is regarded to be ideal for this discovery as it can be collected easily in a minimally invasive manner. Results of the last few years have ascertained the quantification of microRNA (miRNA as a promising approach for the detection and prognostication of cancer. Indeed, an increasing number of studies have shown that circulating cancer-associated miRNAs are readily measured in plasma or serum and they can robustly discriminate cancer patients from healthy controls, as well as distinguishing between good-prognosis and poor-prognosis patients. Furthermore, recent findings also suggest the potential of circulating miRNAs in the screening, monitoring, and treatment of cancer. This article summarizes the most significant and latest discoveries of original researches on circulating miRNAs involvement in cancer, focusing on the potential of circulating miRNAs as minimally invasive biomarkers for cancer theragnosis and prognosis.

  7. Advances in circulating microRNAs as diagnostic and prognostic markers for ovarian cancer

    Institute of Scientific and Technical Information of China (English)

    Hong Zheng; Jia-Yu Liu; Feng-Ju Song; Ke-Xin Chen

    2013-01-01

    Ovarian cancer is one of the most lethal malignant gynecological tumors. More than 70%of patients with ovarian cancer are diagnosed at advanced stage. The 5-year survival in patients with advanced ovarian cancer is less than 30%because of the lack of effective biomarkers for diagnosis, prognosis, and personalized treatment. MicroRNA (miR) is a class of small noncoding RNAs that negatively regulate gene expression primarily through post-transcriptional repression. Many studies on tissue miR in ovarian cancer have been carried out and show great potential in clinical practice. However, tissue samples are not easily available because sampling causes injury. Researchers have started to focus on plasma/serum miR, assuming that blood samples may replace tissue samples in miR research in the future. Plasma/serum miR research is still in its early stages. Studies on its function in the early diagnosis of ovarian cancer have achieved some progress, but plasma/serum miR profiling for prognosis and personalized treatment of ovarian cancer remains unknown. A thorough understanding of the function of plasma/serum miR in ovarian cancer will facilitate early diagnosis and improve treatment for ovarian cancer.

  8. Advances in circulating microRNAs as diagnostic and prognostic markers for ovarian cancer

    International Nuclear Information System (INIS)

    Ovarian cancer is one of the most lethal malignant gynecological tumors. More than 70% of patients with ovarian cancer are diagnosed at advanced stage. The 5-year survival in patients with advanced ovarian cancer is less than 30% because of the lack of effective biomarkers for diagnosis, prognosis, and personalized treatment. MicroRNA (miR) is a class of small noncoding RNAs that negatively regulate gene expression primarily through post-transcriptional repression. Many studies on tissue miR in ovarian cancer have been carried out and show great potential in clinical practice. However, tissue samples are not easily available because sampling causes injury. Researchers have started to focus on plasma/serum miR, assuming that blood samples may replace tissue samples in miR research in the future. Plasma/serum miR research is still in its early stages. Studies on its function in the early diagnosis of ovarian cancer have achieved some progress, but plasma/serum miR profiling for prognosis and personalized treatment of ovarian cancer remains unknown. A thorough understanding of the function of plasma/serum miR in ovarian cancer will facilitate early diagnosis and improve treatment for ovarian cancer

  9. Exosome-encapsulated microRNAs as circulating biomarkers for breast cancer.

    Science.gov (United States)

    Joyce, Doireann P; Kerin, Michael J; Dwyer, Róisín M

    2016-10-01

    Breast cancer is a highly prevalent disease, accounting for 29% of invasive cancers in women. Survival from this disease depends on the stage at diagnosis, with patients who are detected earlier having more favourable outcomes. It is because of this that research groups are focusing on the development of a blood-based biomarker for breast cancer. Such biomarkers may facilitate the detection of breast cancer in its infancy before it has spread beyond the primary site. MicroRNAs (miRNAs) have shown immense potential in this setting. These short, non-coding RNA sequences have been shown to be dysregulated in breast cancer. Despite showing immense promise, miRNAs have not been successfully implemented in the clinical setting due to a lack of a standardised approach which has resulted in conflicting results. These challenges may be addressed at least in part through the study of exosomes. The biomarker potential for exosomes holds huge promise and may revolutionise the way in which we diagnose and manage breast cancer. These nanovesicles may be isolated from a variety of bodily fluids, including serum, and their miRNA content has been shown to reflect that of the parent breast cancer cell. This review will highlight the nomenclature and defining characteristics of exosomes, and current methods of isolation of serum-derived exosomes. Initial promising reports on the potential utility of exosomal miRNAs to be used as breast cancer biomarkers will also be addressed. PMID:27170104

  10. DNA methylation and microRNAs in cancer

    Institute of Scientific and Technical Information of China (English)

    Xiang-Quan Li; Yuan-Yuan Guo; Wei De

    2012-01-01

    DNA methylation is a type of epigenetic modification in the human genome,which means that gene expression is regulated without altering the DNA sequence.Methylation and the relationship between methylation and cancer have been the focus of molecular biology researches.Methylation represses gene expression and can influence embryogenesis and tumorigenesis.In different tissues and at different stages of life,the level of methylation of DNA varies,implying a fundamental but distinct role for methylation.When genes are repressed by abnormal methylation,the resulting effects can include instability of that gene and inactivation of a tumor suppressor gene.MicroRNAs have some aspects in common with this regulation of gene expression.Here we reviewed the influence of gene methylation on cancer and analyzed the methods used to profile methylation.We also assessed the correlation between methylation and other epigenetic modifications and microRNAs.About 55 845 research papers have been published about methylation,and one-fifth of these are about the appearance of methylation in cancer.We conclude that methylation does play a role in some cancer types.

  11. Stability analysis of liver cancer-related microRNAs

    Institute of Scientific and Technical Information of China (English)

    Yan Li; Zhenggang Jiang; Lijian Xu; Hu Yao; Jiangfeng Guo; Xianfeng Ding

    2011-01-01

    MicroRNAs(miRNAs)are non-coding,single-stranded RNAs of ~22 nt and constitute a novel class of gene regulators that are found in both plants and animals.Several studies have demonstrated that serum miRNAs could serve as potential biomarkers for the detection of various cancers and other diseases.A few documents regarding the stability of liver cancer-related miRNAs in serum are available.A systemic analysis of the stability of miRNA in serum is quite necessary.The purpose of this study was to evaluate the stability of miRNAs from three different sources,cultured liver cancer Huh-7 cell line,clinical liver cancer,and serum under different experimental conditions,including different temperature,time duration,pH values,Rnase A digestion,Dnase Ⅰ digestion,and various freeze-thaw cycles.The qRT-PCR analysis demonstrated that liver cancer-related miRNAs were detectable under each of test conditions,indicating that miRNAs were extremely stable and resistant to destruction and degradation under harsh environmental conditions.However,ribosomal RNA was fragile and easily degraded by demonstrating sharp decrease of relative expression under the non-physiological test conditions.We also established a robust procedure for serum RNA extraction,which is greatly important not only for the miRNA profiling studies bat also for the disease prognosis based on abnormal miRNA expression.

  12. Elucidating MicroRNA Regulatory Networks Using Transcriptional, Post-transcriptional, and Histone Modification Measurements

    Directory of Open Access Journals (Sweden)

    Sara J.C. Gosline

    2016-01-01

    Full Text Available MicroRNAs (miRNAs regulate diverse biological processes by repressing mRNAs, but their modest effects on direct targets, together with their participation in larger regulatory networks, make it challenging to delineate miRNA-mediated effects. Here, we describe an approach to characterizing miRNA-regulatory networks by systematically profiling transcriptional, post-transcriptional and epigenetic activity in a pair of isogenic murine fibroblast cell lines with and without Dicer expression. By RNA sequencing (RNA-seq and CLIP (crosslinking followed by immunoprecipitation sequencing (CLIP-seq, we found that most of the changes induced by global miRNA loss occur at the level of transcription. We then introduced a network modeling approach that integrated these data with epigenetic data to identify specific miRNA-regulated transcription factors that explain the impact of miRNA perturbation on gene expression. In total, we demonstrate that combining multiple genome-wide datasets spanning diverse regulatory modes enables accurate delineation of the downstream miRNA-regulated transcriptional network and establishes a model for studying similar networks in other systems.

  13. MicroRNAs transported by exosomes in body fluids as mediators of intercellular communication in cancer.

    Science.gov (United States)

    Salido-Guadarrama, Iván; Romero-Cordoba, Sandra; Peralta-Zaragoza, Oscar; Hidalgo-Miranda, Alfredo; Rodríguez-Dorantes, Mauricio

    2014-01-01

    Cancer-cell communication is an important and complex process, achieved through a diversity of mechanisms that allows tumor cells to mold and influence their environment. In recent years, evidence has accumulated indicating that cells communicate via the release and delivery of microRNAs (miRNAs) packed into tumor-released (TR) exosomes. Understanding the role and mode of action of miRNAs from TR exosomes is of paramount importance in the field of cancer biomarker discovery and for the development of new biomedical applications for cancer therapeutics. In this review, we focus on miRNAs secreted via TR exosomes, which by acting in a paracrine or endocrine manner, facilitate a diversity of signaling mechanisms between cancer cells. We address their contribution as signaling molecules, to the establishment, maintenance, and enhancement of the tumor microenvironment and the metastatic niche in cancer. Finally, we address the potential role of these molecules as biomarkers in cancer diagnosis and prognosis and their impact as a biomedical tool in cancer therapeutics. PMID:25092989

  14. MicroRNA-181b promotes ovarian cancer cell growth and invasion by targeting LATS2

    International Nuclear Information System (INIS)

    Highlights: • miR-181b is upregulated in human ovarian cancer tissues. • miR-181b promotes ovarian cancer cell proliferation and invasion. • LATS2 is a direct target of miR-181b. • LATS2 is involved in miR-181b-induced ovarian cancer cell growth and invasion. - Abstract: MicroRNAs (miRNAs) are strongly implicated in tumorigenesis and metastasis. In this study, we showed significant upregulation of miR-181b in ovarian cancer tissues, compared with the normal ovarian counterparts. Forced expression of miR-181b led to remarkably enhanced proliferation and invasion of ovarian cancer cells while its knockdown induced significant suppression of these cellular events. The tumor suppressor gene, LATS2 (large tumor suppressor 2), was further identified as a novel direct target of miR-181b. Specifically, miR-181b bound directly to the 3′-untranslated region (UTR) of LATS2 and suppressed its expression. Restoration of LATS2 expression partially reversed the oncogenic effects of miR-181b. Our results indicate that miR-181b promotes proliferation and invasion by targeting LATS2 in ovarian cancer cells. These findings support the utility of miR-181b as a potential diagnostic and therapeutic target for ovarian cancer

  15. MicroRNA-181b promotes ovarian cancer cell growth and invasion by targeting LATS2

    Energy Technology Data Exchange (ETDEWEB)

    Xia, Ying; Gao, Yan, E-mail: gaoyanhdhos@126.com

    2014-05-09

    Highlights: • miR-181b is upregulated in human ovarian cancer tissues. • miR-181b promotes ovarian cancer cell proliferation and invasion. • LATS2 is a direct target of miR-181b. • LATS2 is involved in miR-181b-induced ovarian cancer cell growth and invasion. - Abstract: MicroRNAs (miRNAs) are strongly implicated in tumorigenesis and metastasis. In this study, we showed significant upregulation of miR-181b in ovarian cancer tissues, compared with the normal ovarian counterparts. Forced expression of miR-181b led to remarkably enhanced proliferation and invasion of ovarian cancer cells while its knockdown induced significant suppression of these cellular events. The tumor suppressor gene, LATS2 (large tumor suppressor 2), was further identified as a novel direct target of miR-181b. Specifically, miR-181b bound directly to the 3′-untranslated region (UTR) of LATS2 and suppressed its expression. Restoration of LATS2 expression partially reversed the oncogenic effects of miR-181b. Our results indicate that miR-181b promotes proliferation and invasion by targeting LATS2 in ovarian cancer cells. These findings support the utility of miR-181b as a potential diagnostic and therapeutic target for ovarian cancer.

  16. MicroRNA-650 targets ING4 to promote gastric cancer tumorigenicity

    International Nuclear Information System (INIS)

    MicroRNAs (miRNAs) are non-coding RNAs that regulate the expression of target mRNAs. Altered expression of specific miRNAs in human gastric cancer progression has been reported; however, the role of miR-650 in gastric cancer is poorly understood. In this study, we show that miR-650 is involved in lymphatic and distant metastasis in human gastric cancer, and we find that ectopic expression of miR-650 promotes tumorigenesis and proliferation of gastric cancer cells. A luciferase reporter assay demonstrates that Inhibitor of Growth 4 (ING4) is a direct target of miR-650. Collectively, our study demonstrates that over-expression of miR-650 in gastric cancer may promote proliferation and growth of cancer cells, at least partially through directly targeting ING4. These findings help clarify the molecular mechanisms involved in gastric carcinogenesis and indicate that miR-650 modulation may be a bona fide miRNA-based treatment of gastric cancer.

  17. DNA methylation and microRNAs in cancer

    OpenAIRE

    Li, Xiang-Quan; Guo, Yuan-Yuan(Department of Physics, Shanxi University, Taiyuan, Shanxi 030006, China); Wei,, J.B.

    2012-01-01

    DNA methylation is a type of epigenetic modification in the human genome, which means that gene expression is regulated without altering the DNA sequence. Methylation and the relationship between methylation and cancer have been the focus of molecular biology researches. Methylation represses gene expression and can influence embryogenesis and tumorigenesis. In different tissues and at different stages of life, the level of methylation of DNA varies, implying a fundamental but distinct role f...

  18. Biological Networks for Cancer Candidate Biomarkers Discovery

    Science.gov (United States)

    Yan, Wenying; Xue, Wenjin; Chen, Jiajia; Hu, Guang

    2016-01-01

    Due to its extraordinary heterogeneity and complexity, cancer is often proposed as a model case of a systems biology disease or network disease. There is a critical need of effective biomarkers for cancer diagnosis and/or outcome prediction from system level analyses. Methods based on integrating omics data into networks have the potential to revolutionize the identification of cancer biomarkers. Deciphering the biological networks underlying cancer is undoubtedly important for understanding the molecular mechanisms of the disease and identifying effective biomarkers. In this review, the networks constructed for cancer biomarker discovery based on different omics level data are described and illustrated from recent advances in the field.

  19. Biological Networks for Cancer Candidate Biomarkers Discovery.

    Science.gov (United States)

    Yan, Wenying; Xue, Wenjin; Chen, Jiajia; Hu, Guang

    2016-01-01

    Due to its extraordinary heterogeneity and complexity, cancer is often proposed as a model case of a systems biology disease or network disease. There is a critical need of effective biomarkers for cancer diagnosis and/or outcome prediction from system level analyses. Methods based on integrating omics data into networks have the potential to revolutionize the identification of cancer biomarkers. Deciphering the biological networks underlying cancer is undoubtedly important for understanding the molecular mechanisms of the disease and identifying effective biomarkers. In this review, the networks constructed for cancer biomarker discovery based on different omics level data are described and illustrated from recent advances in the field. PMID:27625573

  20. MicroRNA-31 functions as an oncogenic microRNA in mouse and human lung cancer cells by repressing specific tumor suppressors

    DEFF Research Database (Denmark)

    Liu, Xi; Sempere, Lorenzo F; Ouyang, Haoxu; Memoli, Vincent A; Andrew, Angeline S; Luo, Yue; Demidenko, Eugene; Korc, Murray; Shi, Wei; Preis, Meir; Dragnev, Konstantin H; Li, Hua; Direnzo, James; Bak, Mads; Freemantle, Sarah J; Kauppinen, Sakari; Dmitrovsky, Ethan

    2010-01-01

    MicroRNAs (miRNAs) regulate gene expression. It has been suggested that obtaining miRNA expression profiles can improve classification, diagnostic, and prognostic information in oncology. Here, we sought to comprehensively identify the miRNAs that are overexpressed in lung cancer by conducting miRNA...... microarray expression profiling on normal lung versus adjacent lung cancers from transgenic mice. We found that miR-136, miR-376a, and miR-31 were each prominently overexpressed in murine lung cancers. Real-time RT-PCR and in situ hybridization (ISH) assays confirmed these miRNA expression profiles in paired...... normal-malignant lung tissues from mice and humans. Engineered knockdown of miR-31, but not other highlighted miRNAs, substantially repressed lung cancer cell growth and tumorigenicity in a dose-dependent manner. Using a bioinformatics approach, we identified miR-31 target mRNAs and independently...

  1. Circulating microRNAs as specific biomarkers for breast cancer detection.

    Directory of Open Access Journals (Sweden)

    Enders K O Ng

    Full Text Available BACKGROUND: We previously showed microRNAs (miRNAs in plasma are potential biomarkers for colorectal cancer detection. Here, we aimed to develop specific blood-based miRNA assay for breast cancer detection. METHODOLOGY/PRINCIPAL FINDINGS: TaqMan-based miRNA profiling was performed in tumor, adjacent non-tumor, corresponding plasma from breast cancer patients, and plasma from matched healthy controls. All putative markers identified were verified in a training set of breast cancer patients. Selected markers were validated in a case-control cohort of 170 breast cancer patients, 100 controls, and 95 other types of cancers and then blindly validated in an independent set of 70 breast cancer patients and 50 healthy controls. Profiling results showed 8 miRNAs were concordantly up-regulated and 1 miRNA was concordantly down-regulated in both plasma and tumor tissue of breast cancer patients. Of the 8 up-regulated miRNAs, only 3 were significantly elevated (p<0.0001 before surgery and reduced after surgery in the training set. Results from the validation cohort showed that a combination of miR-145 and miR-451 was the best biomarker (p<0.0001 in discriminating breast cancer from healthy controls and all other types of cancers. In the blind validation, these plasma markers yielded Receiver Operating Characteristic (ROC curve area of 0.931. The positive predictive value was 88% and the negative predictive value was 92%. Altered levels of these miRNAs in plasma have been detected not only in advanced stages but also early stages of tumors. The positive predictive value for ductal carcinoma in situ (DCIS cases was 96%. CONCLUSIONS: These results suggested that these circulating miRNAs could be a potential specific biomarker for breast cancer screening.

  2. MicroRNAs in colorectal cancer: A new and promising early diagnostic option

    Directory of Open Access Journals (Sweden)

    Akila Prashant

    2012-01-01

    Full Text Available In spite of advances in diagnostic techniques, surgery, chemotherapy and radiotherapy, colorectal cancers remain undefeated. In the absence of screening, colorectal cancers are diagnosed in an advanced stage when regional and distant metastasis is present. Hence, the hope for control is primary prevention or early diagnosis. Western lifestyle and diet have been implicated in the causation of colon cancers. However, it is still a controversy whether this is due to excess calories, high fat content, genotoxic agents, or lack of protective agents present in vegetables and fruits. Therefore, recommending a specific cancer prevention diet can have fallacies. In this context reduction in cancer mortality can be achieved by screening population at high risk. The colorectal cancers require investigative modalities like colonoscopy, sigmoidoscopy or fecal occult blood testing (FOBT for screening. Colonoscopy is the most sensitive and specific of all the available colorectal screening tests, whereas the sensitivity and specificity for FOBT and sigmoidoscopy are much lower. Although performance of FOBT is relatively inexpensive, sigmoidoscopy and colonoscopy must be performed by trained endoscopists and are more expensive. Moreover, lack of awareness that colorectal cancer is a prevalent and serious disease, concerns about the potential discomforts of colorectal cancer procedures or of the preparations for screening appear to be potential barriers for colorectal cancer screening. MicroRNAs (miRNAs have roles in colon carcinogenesis; therefore, may be useful biomarkers for colorectal carcinoma (CRC. They are short ribonucleic acid (RNA molecules having very few nucleotides compared with other RNAs. miRNAs have been studied intensively in the field of oncological research, and emerging evidence suggests that altered miRNA regulation is involved in the pathogenesis of cancers. This review summarizes the use of miRNA in the early diagnosis of colorectal

  3. A long non-coding RNA targets microRNA miR-34a to regulate colon cancer stem cell asymmetric division

    Science.gov (United States)

    Wang, Lihua; Bu, Pengcheng; Ai, Yiwei; Srinivasan, Tara; Chen, Huanhuan Joyce; Xiang, Kun; Lipkin, Steven M; Shen, Xiling

    2016-01-01

    The roles of long non-coding RNAs (lncRNAs) in regulating cancer and stem cells are being increasingly appreciated. Its diverse mechanisms provide the regulatory network with a bigger repertoire to increase complexity. Here we report a novel LncRNA, Lnc34a, that is enriched in colon cancer stem cells (CCSCs) and initiates asymmetric division by directly targeting the microRNA miR-34a to cause its spatial imbalance. Lnc34a recruits Dnmt3a via PHB2 and HDAC1 to methylate and deacetylate the miR-34a promoter simultaneously, hence epigenetically silencing miR-34a expression independent of its upstream regulator, p53. Lnc34a levels affect CCSC self-renewal and colorectal cancer (CRC) growth in xenograft models. Lnc34a is upregulated in late-stage CRCs, contributing to epigenetic miR-34a silencing and CRC proliferation. The fact that lncRNA targets microRNA highlights the regulatory complexity of non-coding RNAs (ncRNAs), which occupy the bulk of the genome. DOI: http://dx.doi.org/10.7554/eLife.14620.001 PMID:27077950

  4. Lung Cancer:MicroRNA and Target Database%Lung Cancer: MicroRNA and Target Database

    Institute of Scientific and Technical Information of China (English)

    Challa KIRAN; Ponnala DEEPIKA

    2012-01-01

    MicroRNAs (miRNAs) are a class of non-coding RNAs that hybridize to mRNAs and induce either translation repression or mRNA cleavage.Recently,it has been reported that miRNAs could possibly play a critical role in cellular processes like regulation of cell growth,differentiation,and apoptosis,emphasizing their role in tumorigenesis.Likewise,several miRNA's are involved in lung cancer tumorigenesis.The present review puts forth a database of human miRNA's involved in lung cancer along with their target genes.It also provides sequences of miRNA's and their chromosomal locations retrieved from different databases like microCosm (218 microRNAs),PhenomiR (293 microRNAs),and mir2Disease (90 microRNAs) and target gene information such as the pathways like cell cycle regulation,angiogenesis,apoptosis etc.Though miRNA's are still to be explored,they hold a promise as therapeutic targets and diagnostic markers of cancer.

  5. The secret role of microRNAs in cancer stem cell development and potential therapy: A Notch-pathway approach.

    Directory of Open Access Journals (Sweden)

    Marianna eProkopi

    2015-02-01

    Full Text Available MicroRNAs (miRNAs have been implicated in the development of some if not all cancer types and have been identified as attractive targets for prognosis, diagnosis and therapy of the disease. MiRNAs are a class of small non-coding RNAs (20-22 nucleotides in length that bind imperfectly to the 3’-untranslated region of target mRNA regulating gene expression. Aberrantly expressed miRNAs in cancer, sometimes known as oncomiRNAs, have been shown to play a major role in oncogenesis, metastasis and drug resistance. Amplification of oncomiRNAs during cancer development correlates with the silencing of tumor suppressor genes; on the other hand, down-regulation of miRNAs has also been observed in cancer and cancer stem cells (CSCs. In both cases, miRNA regulation is inversely correlated with cancer progression. Growing evidence indicates that miRNAs are also involved in the metastatic process by either suppressing or promoting metastasis-related genes leading to the reduction or activation of cancer cell migration and invasion processes. In particular, circulating miRNAs (vesicle-encapsulated or non-encapsulated have significant effects on tumorigenesis: membrane-particles, apoptotic bodies and exosomes have been described as providers of a cell-to-cell communication system transporting oncogenic miRNAs from tumors to neighboring cells and distant metastatic sites. It is hypothesized that MiRNAs control cancer development in a traditional manner, by regulating signaling pathways and factors. In addition, recent developments indicate a non-conventional mechanism of cancer regulation by stem cell reprogramming via a regulatory network consisting of miRNAs and Wnt/β-catenin, Notch, and Hedgehog signaling pathways, all of which are involved in controlling stem cell functions of CSCs. In this review, we focus on the role of miRNAs in the Notch pathway and how they regulate CSC self-renewal, differentiation and tumorigenesis by direct/indirect targeting of

  6. Alterations of MicroRNAs in Solid Cancers and Their Prognostic Value

    International Nuclear Information System (INIS)

    MicroRNAs (miRNAs) are evolutionarily conserved, naturally abundant, small, regulatory non-coding RNAs that inhibit gene expression at the post-transcriptional level in a sequence-specific manner. Each miRNA represses the protein expression of several coding genes in a manner proportional to the sequence complementarity with the target transcripts. MicroRNAs play key regulatory roles in organismal development and homeostasis. They control fundamental biological processes, such as stem-cell regulation and cellular metabolism, proliferation, differentiation, stress resistance, and apoptosis. Differential miRNA expression is found in malignant tumors in comparison to normal tissue counterparts. This indicates that miRNA deregulation contributes to the initiation and progression of cancer. Currently, miRNA expression signatures are being rigorously investigated in various tumor types, with the aim of developing novel, efficient biomarkers that can improve clinical management of cancer patients. This review discusses deregulated miRNAs in solid tumors, and focuses on their emerging prognostic potential

  7. Emerging role of microRNAs in cancer stem cells:Implications in cancer therapy

    Institute of Scientific and Technical Information of China (English)

    Minal; Garg

    2015-01-01

    A small subset of cancer cells that act as tumor initiating cells or cancer stem cells(CSCs) maintain self-renewal and growth promoting capabilities of cancer and are responsible for drug/treatment resistance,tumor recurrence and metastasis. Due to their potential clinical importance,many researchers have put their efforts over decades to unravel the molecular mechanisms that regulate CSCs functions. Micro RNAs(mi RNAs) which are 21-23 nucleotide long,endogenous noncoding RNAs,regulate gene expression through gene silencing at post-transcriptional level by binding to the 3’-untranslated regions or the open reading frames of target genes,thereby result in target mR NA degradation or its translational repression and serve important role in several cellular,physiological and developmental processes. Aberrant mi RNAs expression and their implication in CSCs regulation by controlling asymmetric cell division,drug/treatment resistance and metastasis make mi RNAs a tool of great therapeutic potential against cancer. Recent advancements on the biological complexities of CSCs,modulation in CSCs properties by mi RNA network and development of mi RNA based treatment strategies specifically targeting the CSCs as an attractive therapeutic targets for clinical application are being critically analysed.

  8. Up-regulation of microRNA-10b is associated with the development of breast cancer brain metastasis

    OpenAIRE

    Ahmad, Aamir; Sethi, Seema; Chen, Wei; Ali-Fehmi, Rouba; Mittal, Sandeep; Fazlul H. Sarkar

    2014-01-01

    Brain metastases from primary breast cancer are difficult to treat and associated with poor prognosis. Our understanding of the molecular basis for the development of such cancers is sparse. We hypothesized that the pro-metastatic microRNA-10b (miR-10b) plays a role in breast cancer brain metastasis. The study cohort comprised of twenty patients with breast cancer and brain metastasis as well as ten control patients (age, stage, and follow-up matched) with breast cancer without brain metastas...

  9. Theragnosis-based combined cancer therapy using doxorubicin-conjugated microRNA-221 molecular beacon.

    Science.gov (United States)

    Lee, Jonghwan; Choi, Kyung-Ju; Moon, Sung Ung; Kim, Soonhag

    2016-01-01

    Recently, microRNA (miRNA or miR) has emerged as a new cancer biomarker because of its high expression level in various cancer types and its role in the control of tumor suppressor genes. In cancer studies, molecular imaging and treatment based on target cancer markers have been combined to facilitate simultaneous cancer diagnosis and therapy. In this study, for combined therapy with diagnosis of cancer, we developed a doxorubicin-conjugated miR-221 molecular beacon (miR-221 DOXO MB) in a single platform composed of three different nucleotides: miR-221 binding sequence, black hole quencher 1 (BHQ1), and doxorubicin binding site. Imaging of endogenous miR-221 was achieved by specific hybridization between miR-221 and the miR-221 binding site in miR-221 DOXO MB. The presence of miR-221 triggered detachment of the quencher oligo and subsequent activation of a fluorescent signal of miR-221 DOXO MB. Simultaneous cancer therapy in C6 astrocytoma cells and nude mice was achieved by inhibition of miRNA-221 function that downregulates tumor suppressor genes. The detection of miR-221 expression and inhibition of miR-221 function by miR-221 DOXO MB provide the feasibility as a cancer theragnostic probe. Furthermore, a cytotoxic effect was induced by unloading of doxorubicin intercalated into miR-221 DOXO MB inside cells. Loss of miR-221 function and cytotoxicity induced by the miR-221 DOXO MB provides combined therapeutic efficacy against cancers. This method could be used as a new theragnostic probe with enhanced therapy to detect and inhibit many cancer-related miRNAs. PMID:26454049

  10. Role of microRNAs in the Therapeutic Effects of Curcumin in Non-Cancer Diseases.

    Science.gov (United States)

    Momtazi, Amir Abbas; Derosa, Giuseppe; Maffioli, Pamela; Banach, Maciej; Sahebkar, Amirhossein

    2016-08-01

    Curcumin is a bioactive polyphenol occurring in the rhizomes of Curcuma longa. It is well-reputed for its chemopreventive and anticancer properties; however, recent evidence has revealed numerous biological and pharmacological effects of curcumin that are relevant to the treatment of non-cancer diseases. Mechanistically, curcumin exerts its pharmacological effects through anti-inflammatory and antioxidant mechanisms via interaction with different signaling molecules and transcription factors. In addition, epigenetic modulators such as microRNAs (miRs) have emerged as novel targets of curcumin. Curcumin was found to modulate the expression of several pathogenic miRs in brain, ocular, renal, and liver diseases. The present systematic review was conducted to identify miRs that are regulated by curcumin in non-cancer diseases. PMID:27241179

  11. Network systems biology for targeted cancer therapies

    Institute of Scientific and Technical Information of China (English)

    Ting-Ting Zhou

    2012-01-01

    The era of targeted cancer therapies has arrived.However,due to the complexity of biological systems,the current progress is far from enough.From biological network modeling to structural/dynamic network analysis,network systems biology provides unique insight into the potential mechanisms underlying the growth and progression of cancer cells.It has also introduced great changes into the research paradigm of cancer-associated drug discovery and drug resistance.

  12. MicroRNAs Induce Epigenetic Reprogramming and Suppress Malignant Phenotypes of Human Colon Cancer Cells.

    Directory of Open Access Journals (Sweden)

    Hisataka Ogawa

    Full Text Available Although cancer is a genetic disease, epigenetic alterations are involved in its initiation and progression. Previous studies have shown that reprogramming of colon cancer cells using Oct3/4, Sox2, Klf4, and cMyc reduces cancer malignancy. Therefore, cancer reprogramming may be a useful treatment for chemo- or radiotherapy-resistant cancer cells. It was also reported that the introduction of endogenous small-sized, non-coding ribonucleotides such as microRNA (miR 302s and miR-369-3p or -5p resulted in the induction of cellular reprogramming. miRs are smaller than the genes of transcription factors, making them possibly suitable for use in clinical strategies. Therefore, we reprogrammed colon cancer cells using miR-302s and miR-369-3p or -5p. This resulted in inhibition of cell proliferation and invasion and the stimulation of the mesenchymal-to-epithelial transition phenotype in colon cancer cells. Importantly, the introduction of the ribonucleotides resulted in epigenetic reprogramming of DNA demethylation and histone modification events. Furthermore, in vivo administration of the ribonucleotides in mice elicited the induction of cancer cell apoptosis, which involves the mitochondrial Bcl2 protein family. The present study shows that the introduction of miR-302s and miR-369s could induce cellular reprogramming and modulate malignant phenotypes of human colorectal cancer, suggesting that the appropriate delivery of functional small-sized ribonucleotides may open a new avenue for therapy against human malignant tumors.

  13. MicroRNAs Induce Epigenetic Reprogramming and Suppress Malignant Phenotypes of Human Colon Cancer Cells.

    Science.gov (United States)

    Ogawa, Hisataka; Wu, Xin; Kawamoto, Koichi; Nishida, Naohiro; Konno, Masamitsu; Koseki, Jun; Matsui, Hidetoshi; Noguchi, Kozou; Gotoh, Noriko; Yamamoto, Tsuyoshi; Miyata, Kanjiro; Nishiyama, Nobuhiro; Nagano, Hiroaki; Yamamoto, Hirofumi; Obika, Satoshi; Kataoka, Kazunori; Doki, Yuichiro; Mori, Masaki; Ishii, Hideshi

    2015-01-01

    Although cancer is a genetic disease, epigenetic alterations are involved in its initiation and progression. Previous studies have shown that reprogramming of colon cancer cells using Oct3/4, Sox2, Klf4, and cMyc reduces cancer malignancy. Therefore, cancer reprogramming may be a useful treatment for chemo- or radiotherapy-resistant cancer cells. It was also reported that the introduction of endogenous small-sized, non-coding ribonucleotides such as microRNA (miR) 302s and miR-369-3p or -5p resulted in the induction of cellular reprogramming. miRs are smaller than the genes of transcription factors, making them possibly suitable for use in clinical strategies. Therefore, we reprogrammed colon cancer cells using miR-302s and miR-369-3p or -5p. This resulted in inhibition of cell proliferation and invasion and the stimulation of the mesenchymal-to-epithelial transition phenotype in colon cancer cells. Importantly, the introduction of the ribonucleotides resulted in epigenetic reprogramming of DNA demethylation and histone modification events. Furthermore, in vivo administration of the ribonucleotides in mice elicited the induction of cancer cell apoptosis, which involves the mitochondrial Bcl2 protein family. The present study shows that the introduction of miR-302s and miR-369s could induce cellular reprogramming and modulate malignant phenotypes of human colorectal cancer, suggesting that the appropriate delivery of functional small-sized ribonucleotides may open a new avenue for therapy against human malignant tumors. PMID:25970424

  14. Potential role of microRNA-126 in the diagnosis of cancers

    Science.gov (United States)

    Yan, Jin; Ma, Shijie; Zhang, Yifeng; Yin, Chengqiang; Zhou, Xiaoying; Zhang, Guoxin

    2016-01-01

    Abstract Background: Cancer has become a major public concern all over the world and early diagnosis of cancer is of great benefit for treatment and prognosis. Several studies have investigated the association between abnormal circulating microRNA-126 (miR-126) expression and the risk of various cancers, but the results are inconsistent. Therefore, this meta-analysis was carried out to assess the potential diagnostic value of miR-126 for cancer. Methods: Relevant studies were searched from PubMed, Embase, and Web of Science and we calculated the pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the summary receiver operator characteristic curve (AUC) to assess the diagnostic value of miR-126 for cancer detection. Results: A total of 745 cancer patients and 749 controls from 11 studies of 7 papers were included in this meta-analysis. The summary estimates revealed that the pooled sensitivity was 68% (95% confidence interval [CI]: 60–75%), the specificity was 76% (95% CI: 65–85%), the PLR was 2.87 (95% CI: 1.96–4.21), the NLR was 0.42 (95% CI: 0.35–0.52), the DOR was 7 (95% CI: 4–11), and the AUC was 0.77 (95%CI: 0.73–0.80). Moreover, the sample type, cancer type, sample size, and quality score might be sources of heterogeneity. Conclusion: This systematic review and meta-analysis suggests that miR-126 has great potential to be a noninvasive biomarker in the diagnosis of cancer. However, more well-designed studies with larger sample size on the diagnostic value of miR-126 for cancer are needed in the future. PMID:27583885

  15. Analysis of microarray-identified genes and microRNAs associated with drug resistance in ovarian cancer

    OpenAIRE

    Zou, Jing; Yin, Fuqiang; Wang, Qi; Zhang, Wei; Li, Li

    2015-01-01

    The aim of this study was to identify potential microRNAs and genes associated with drug resistance in ovarian cancer through web-available microarrays. The drug resistant-related microRNA microarray dataset GS54665 and mRNA dataset GSE33482, GSE28646, and GSE15372 were downloaded from the Gene Expression Omnibus database. Dysregulated microRNAs/genes were screened with GEO2R and were further identified in SKOV3 (SKOV3/DDP) and A2780 (A2780/DDP) cells by real-time quantitative PCR (qRT-PCR), ...

  16. Optimized high-throughput microRNA expression profiling provides novel biomarker assessment of clinical prostate and breast cancer biopsies

    OpenAIRE

    Fedele Vita; Scott Gary K; Wong Linda; Sensinger Kelly; Bowers Jessica; Benz Christopher C; Mattie Michael D; Ginzinger David; Getts Robert; Haqq Chris

    2006-01-01

    Abstract Background Recent studies indicate that microRNAs (miRNAs) are mechanistically involved in the development of various human malignancies, suggesting that they represent a promising new class of cancer biomarkers. However, previously reported methods for measuring miRNA expression consume large amounts of tissue, prohibiting high-throughput miRNA profiling from typically small clinical samples such as excision or core needle biopsies of breast or prostate cancer. Here we describe a no...

  17. Diagnostic and prognostic microRNAs in the serum of breast cancer patients measured by droplet digital PCR

    OpenAIRE

    Mangolini, Alessandra; Ferracin, Manuela; Zanzi, Maria Vittoria; Saccenti, Elena; Ebnaof, Sayda Omer; Poma, Valentina Vultaggio; Sanz, Juana M.; Passaro, Angela; Pedriali, Massimo; Frassoldati, Antonio; Querzoli, Patrizia; Sabbioni, Silvia; Carcoforo, Paolo; Hollingsworth, Alan; Negrini, Massimo

    2015-01-01

    Background Breast cancer circulating biomarkers include carcinoembryonic antigen and carbohydrate antigen 15–3, which are used for patient follow-up. Since sensitivity and specificity are low, novel and more useful biomarkers are needed. The presence of stable circulating microRNAs (miRNAs) in serum or plasma suggested a promising role for these tiny RNAs as cancer biomarkers. To acquire an absolute concentration of circulating miRNAs and reduce the impact of preanalytical and analytical vari...

  18. Polymorphisms of the Hypoxia Inducible Factor 1 and microRNA Related Genes and the Susceptibility and Survival of Lung Cancer and Upper Aero-Digestive Tract Cancers

    OpenAIRE

    Yang, Ying

    2014-01-01

    Background: Hypoxia inducible factor 1(HIF-1) and microRNAs (miRNAs) regulate transcriptional activities and contribute in several biological processes such as oxygen homeostasis, cell growth, progression and apoptosis that are important in lung and upper aero-digestive tract (UADT) cancer etiology and outcomes. Nonetheless, there are few published studies of the relationship between HIF-1 and miRNA gene polymorphisms and susceptibility and survival of lung cancer or UADT cancers. Methods: 1,...

  19. From microRNA functions to microRNA therapeutics: Novel targets and novel drugs in breast cancer research and treatment

    OpenAIRE

    Piva, Roberta; Spandidos, Demetrios A.; Gambari, Roberto

    2013-01-01

    MicroRNAs (miRNAs or miRs) are a family of small non-coding RNAs that regulate gene expression by the sequence-selective targeting of mRNAs, leading to translational repression or mRNA degradation, depending on the degree of complementarity with target mRNA sequences. miRNAs play a crucial role in cancer. In the case of breast tumors, several studies have demonstrated a correlation between: i) the expression profile of oncogenic miRNAs (oncomiRs) or tumor suppressor miRNAs and ii) the tumorig...

  20. Assessment of Circulating microRNAs in Plasma of Lung Cancer Patients

    Directory of Open Access Journals (Sweden)

    Orazio Fortunato

    2014-03-01

    Full Text Available Lung cancer is the most common cause of cancer deaths worldwide and numerous ongoing research efforts are directed to identify new strategies for its early detection. The development of non-invasive blood-based biomarkers for cancer detection in its preclinical phases is crucial to improve the outcome of this deadly disease. MicroRNAs (miRNAs are a new promising class of circulating biomarkers for cancer detection and prognosis definition, but lack of consensus on data normalization methods for circulating miRNAs and the critical issue of haemolysis, has affected the identification of circulating miRNAs with diagnostic potential. We describe here an interesting approach for profiling circulating miRNAs in plasma samples based on the evaluation of reciprocal miRNA levels measured by quantitative Real-Time PCR. By monitoring changes of plasma miRNA-ratios, it is possible to assess the deregulation of tumor-related miRNAs and identify signatures with diagnostic and prognostic value. In addition, to avoid bias due to the release of miRNAs from blood cells, a miRNA-ratios signature distinguishing haemolyzed samples was identified. The method described was validated in plasma samples of lung cancer patients, but given its reproducibility and reliability, could be potentially applied for the identification of diagnostic circulating miRNAs in other diseases.

  1. MicroRNA-29a Promotes Pancreatic Cancer Growth by Inhibiting Tristetraprolin

    Directory of Open Access Journals (Sweden)

    Xian-Jun Sun

    2015-09-01

    Full Text Available Background/Aims: The microRNA (miR 29 family has been studied extensively for its involvement in several diseases, and aberrant expression of its members is associated with tumorigenesis and cancer progression. Here, we examined the role of miR-29a in pancreatic cancer and the involvement of tristetraprolin (TTP. Methods: We monitored miR-29a and TTP expression in pancreatic cancer by qRT-PCR and western blotting. The effect of miR-29a on pancreatic cancer was determined through MTT assay and migration assay. The results were validated in the tumorigenesis model. Results: We found that miR-29a was up regulated in pancreatic tumor tissues and cell lines and positively correlated with metastasis. Ectopic expression of miR-29a increased the expression of pro-inflammatory factors and epithelial-mesenchymal transition (EMT markers, through down regulating TTP. TTP was down regulated in tumor tissues, and its ectopic expression decreased cell viability and migration in vitro, inhibited tumor growth and the EMT phenotype in vivo, and reversed the effect of miR-29a on tumor cell proliferation and invasion in vitro and in vivo. Conclusion: Our results suggest that miR-29a acts as an oncogene by down regulating TTP and provide the basis for further studies exploring the potential of miR-29a and TTP as biomarkers and targets for the treatment of pancreatic cancer.

  2. OncomiR or Tumor Suppressor? The Duplicity of MicroRNAs in Cancer.

    Science.gov (United States)

    Svoronos, Alexander A; Engelman, Donald M; Slack, Frank J

    2016-07-01

    MicroRNAs (miRNA) are short, noncoding RNAs whose dysregulation has been implicated in most, if not all, cancers. They regulate gene expression by suppressing mRNA translation and reducing mRNA stability. To this end, there is a great deal of interest in modifying miRNA expression levels for the treatment of cancer. However, the literature is fraught with inconsistent accounts as to whether various miRNAs are oncogenic or tumor suppressive. In this review, we directly examine these inconsistencies and propose several mechanisms to explain them. These mechanisms include the possibility that specific miRNAs can simultaneously produce competing oncogenic and tumor suppressive effects by suppressing both tumor suppressive mRNAs and oncogenic mRNAs, respectively. In addition, miRNAs can modulate tumor-modifying extrinsic factors, such as cancer-immune system interactions, stromal cell interactions, oncoviruses, and sensitivity to therapy. Ultimately, it is the balance between these processes that determines whether a specific miRNA produces a net oncogenic or net tumor suppressive effect. A solid understanding of this phenomenon will likely prove valuable in evaluating miRNA targets for cancer therapy. Cancer Res; 76(13); 3666-70. ©2016 AACR. PMID:27325641

  3. The Cancer Prevention and Control Research Network

    Directory of Open Access Journals (Sweden)

    Jeffrey R. Harris, MD, MPH, MBA

    2005-01-01

    Full Text Available The Cancer Prevention and Control Research Network is a national network recently established to focus on developing new interventions and disseminating and translating proven interventions into practice to reduce cancer burden and disparities, especially among minority and medically underserved populations. Jointly funded by the Centers for Disease Control and Prevention and the National Cancer Institute, the Cancer Prevention and Control Research Network consists of sites administered through Prevention Research Centers funded by the Centers for Disease Control and Prevention. The five sites are located in Kentucky, Massachusetts, South Carolina, Texas, Washington State, and West Virginia. The Cancer Prevention and Control Research Network’s intervention areas include primary prevention of cancer through healthy eating, physical activity, sun avoidance, tobacco control, and early detection of cancer through screening. The Cancer Prevention and Control Research Network uses the methods of community-based participatory research and seeks to build on the cancer-relevant systematic reviews of the Guide to Community Preventive Services. Initial foci for the Cancer Prevention and Control Research Network’s research work groups include projects to increase screening for breast, cervical, and colorectal cancers; to promote informed decision making for prostate cancer screening; and to validate educational materials developed for low-literacy populations.

  4. A key role of microRNA-29b for the suppression of colon cancer cell migration by American ginseng.

    Directory of Open Access Journals (Sweden)

    Deepak Poudyal

    Full Text Available Metastasis of colon cancer cells increases the risk of colon cancer mortality. We have recently shown that American ginseng prevents colon cancer, and a Hexane extract of American Ginseng (HAG has particularly potent anti-inflammatory and anti-cancer properties. Dysregulated microRNA (miR expression has been observed in several disease conditions including colon cancer. Using global miR expression profiling, we observed increased miR-29b in colon cancer cells following exposure to HAG. Since miR-29b plays a role in regulating the migration of cancer cells, we hypothesized that HAG induces miR-29b expression to target matrix metalloproteinase-2 (MMP-2 thereby suppressing the migration of colon cancer cells. Results are consistent with this hypothesis. Our study supports the understanding that targeting MMP-2 by miR-29b is a mechanism by which HAG suppresses the migration of colon cancer cells.

  5. MicroRNA 421 suppresses DPC4/Smad4 in pancreatic cancer

    Energy Technology Data Exchange (ETDEWEB)

    Hao, Jun [Department of Pancreatic Surgery, Changhai Hospital, Second Military Medical University, Shanghai 200433 (China); Zhang, Shuyu [School of Radiation Medicine and Public Health, Medical College of Soochow University, Suzhou 215123 (China); Zhou, Yingqi [Department of Pancreatic Surgery, Changhai Hospital, Second Military Medical University, Shanghai 200433 (China); Liu, Cong [Department of Radiation Medicine, Faculty of Naval Medicine, Second Military Medical University, Xiangyin Road, Shanghai 200433 (China); Hu, Xiangui, E-mail: xianguihu@yahoo.com.cn [Department of Pancreatic Surgery, Changhai Hospital, Second Military Medical University, Shanghai 200433 (China); Shao, Chenghao, E-mail: schhao@133sh.com [Department of Pancreatic Surgery, Changhai Hospital, Second Military Medical University, Shanghai 200433 (China)

    2011-03-25

    Research highlights: {yields} We identify miR-421 as a novel potential regulator of DPC4/Smad4. {yields} The expression levels of miR-421 and DPC4/Smad4 are inversely correlated in human clinical specimens of pancreatic cancer. {yields} Overexpression of miR-421 represses the reporter activities driven by the 3'-UTR of DPC4/Smad4 and DPC4/Smad4 protein level in pancreatic cancer cell. {yields} Ectopic expression of miR-421 promotes the proliferation and colony formation of pancreatic cancer cell. -- Abstract: MicroRNAs (miRNAs) have emerged as important regulators in the development of pancreatic cancer and may be a valuable therapeutic application. DPC4/Smad4 is a critical tumor suppressor involved in the progression of pancreatic cancer, but few studies have been conducted to determine its relationship with miRNAs. In this study, we identify miR-421 as a potential regulator of DPC4/Smad4. We find that in human clinical specimens of pancreatic cancer miR-421 is aberrantly upregulated while DPC4/Smad4 is strongly repressed, and their levels of expression are inversely correlated. Moreover, ectopic expression of miR-421 significantly decreases DPC4/Smad4 protein level in pancreatic cancer cell lines and simultaneously promotes cell proliferation and colony formation in vitro. Our findings identify miR-421 as a potent regulator of DPC4/Smad4, which may provide a novel therapeutic strategy for treatment of DPC4/Smad4-driven pancreatic cancer.

  6. MicroRNA 421 suppresses DPC4/Smad4 in pancreatic cancer

    International Nuclear Information System (INIS)

    Research highlights: → We identify miR-421 as a novel potential regulator of DPC4/Smad4. → The expression levels of miR-421 and DPC4/Smad4 are inversely correlated in human clinical specimens of pancreatic cancer. → Overexpression of miR-421 represses the reporter activities driven by the 3'-UTR of DPC4/Smad4 and DPC4/Smad4 protein level in pancreatic cancer cell. → Ectopic expression of miR-421 promotes the proliferation and colony formation of pancreatic cancer cell. -- Abstract: MicroRNAs (miRNAs) have emerged as important regulators in the development of pancreatic cancer and may be a valuable therapeutic application. DPC4/Smad4 is a critical tumor suppressor involved in the progression of pancreatic cancer, but few studies have been conducted to determine its relationship with miRNAs. In this study, we identify miR-421 as a potential regulator of DPC4/Smad4. We find that in human clinical specimens of pancreatic cancer miR-421 is aberrantly upregulated while DPC4/Smad4 is strongly repressed, and their levels of expression are inversely correlated. Moreover, ectopic expression of miR-421 significantly decreases DPC4/Smad4 protein level in pancreatic cancer cell lines and simultaneously promotes cell proliferation and colony formation in vitro. Our findings identify miR-421 as a potent regulator of DPC4/Smad4, which may provide a novel therapeutic strategy for treatment of DPC4/Smad4-driven pancreatic cancer.

  7. Exploring circulating micro-RNA in the neoadjuvant treatment of breast cancer.

    Science.gov (United States)

    Casey, Máire-Caitlín; Sweeney, Karl J; Brown, James Andrew Lawrence; Kerin, Michael J

    2016-07-01

    Breast cancer is the most frequently diagnosed malignancy amongst females worldwide. In recent years the management of this disease has transformed considerably, including the administration of chemotherapy in the neoadjuvant setting. Aside from increasing rates of breast conserving surgery and enabling surgery via tumour burden reduction, use of chemotherapy in the neoadjuvant setting allows monitoring of in vivo tumour response to chemotherapeutics. Currently, there is no effective means of identifying chemotherapeutic responders from non-responders. Whilst some patients achieve complete pathological response (pCR) to chemotherapy, a good prognostic index, a proportion of patients derive little or no benefit, being exposed to the deleterious effects of systemic treatment without any knowledge of whether they will receive benefit. The identification of predictive and prognostic biomarkers could confer multiple benefits in this setting, specifically the individualization of breast cancer management and more effective administration of chemotherapeutics. In addition, biomarkers could potentially expedite the identification of novel chemotherapeutic agents or increase their efficacy. Micro-RNAs (miRNAs) are small non-coding RNA molecules. With their tissue-specific expression, correlation with clinicopathological prognostic indices and known dysregulation in breast cancer, miRNAs have quickly become an important avenue in the search for novel breast cancer biomarkers. We provide a brief history of breast cancer chemotherapeutics and explore the emerging field of circulating (blood-borne) miRNAs as breast cancer biomarkers for the neoadjuvant treatment of breast cancer. Established molecular markers of breast cancer are outlined, while the potential role of circulating miRNAs as chemotherapeutic response predictors, prognosticators or potential therapeutic targets is discussed. PMID:26756433

  8. NFκB-mediated cyclin D1 expression by microRNA-21 influences renal cancer cell proliferation

    OpenAIRE

    Bera, Amit; Ghosh-Choudhury, Nandini; Dey, Nirmalya; Das, Falguni; Kasinath, Balakuntalam S.; Abboud, Hanna E.; Choudhury, Goutam Ghosh

    2013-01-01

    MicroRNAs regulate post-transcriptomic landscape in many tumors including renal cell carcinoma. We have recently shown significantly increased expression of miR-21 in renal tumors and that this miRNA contributes to the proliferation of renal cancer cells in culture. However, the mechanism by which miR-21 regulates renal cancer cells proliferation is poorly understood. Addiction to constitutive NFκB activity is hallmark of many cancers including renal cancer. Using miR-21 Sponge in renal cance...

  9. Targeting MicroRNA in Cancer Using Plant-Based Proanthocyanidins

    Directory of Open Access Journals (Sweden)

    Rishipal R. Bansode

    2016-04-01

    Full Text Available Proanthocyanidins are oligomeric flavonoids found in plant sources, most notably in apples, cinnamon, grape skin and cocoa beans. They have been also found in substantial amounts in cranberry, black currant, green tea, black tea and peanut skins. These compounds have been recently investigated for their health benefits. Proanthocyanidins have been demonstrated to have positive effects on various metabolic disorders such as inflammation, obesity, diabetes and insulin resistance. Another upcoming area of research that has gained widespread interest is microRNA (miRNA-based anticancer therapies. MicroRNAs are short non-coding RNA segments, which plays a crucial role in RNA silencing and post-transcriptional regulation of gene expression. Currently, miRNA based anticancer therapies are being investigated either alone or in combination with current treatment methods. In this review, we summarize the current knowledge and investigate the potential of naturally occurring proanthocyanidins in modulating miRNA expression. We will also assess the strategies and challenges of using this approach as potential cancer therapeutics.

  10. microRNA Expression Profiling of Side Population Cells in Human Lung Cancer and Preliminary Analysis

    Directory of Open Access Journals (Sweden)

    Xiaotao XU

    2010-07-01

    Full Text Available Background and objective Recent studies indicate that the side population (SP which is an enriched source of cancer stem cells (CSCs is the root cause of tumor growth and development. SP appears to be highly resistant to chemo- and radio-therapy which becomes an important factor in tumor recurrence and metastasis. The aim of this study is to determine the difference of microRNA expression profiles between SP cells and non-SP cells so as to lay necessary basis for research on the function of miRNA in lung cancer stem cells. Methods SP and non-SP cells were isolated using flow cytometry and Hoechst 33342 dye efflux assay from human lung adenocarcinoma A549 cell. The total RNA was extracted. The microarray detection system was employed to analyze whether there was difference in miRNA expression profile between SP and non-SP cells. Results A total of 85 differentially expressed miRNA were found, including 32 over-expression and 53 low-expression miRNA in SP. Conclusion miRNA may play important roles in tumorigenesis of lung cancer stem cell. The study of miRNA contributes to elucidate the molecular mechanism of lung cancer stem cell.

  11. Regulation of MicroRNAs by Natural Agents: New Strategies in Cancer Therapies

    Directory of Open Access Journals (Sweden)

    Neoh Hun Phuah

    2014-01-01

    Full Text Available MicroRNAs (miRNAs are short noncoding RNA which regulate gene expression by messenger RNA (mRNA degradation or translation repression. The plethora of published reports in recent years demonstrated that they play fundamental roles in many biological processes, such as carcinogenesis, angiogenesis, programmed cell death, cell proliferation, invasion, migration, and differentiation by acting as tumour suppressor or oncogene, and aberrations in their expressions have been linked to onset and progression of various cancers. Furthermore, each miRNA is capable of regulating the expression of many genes, allowing them to simultaneously regulate multiple cellular signalling pathways. Hence, miRNAs have the potential to be used as biomarkers for cancer diagnosis and prognosis as well as therapeutic targets. Recent studies have shown that natural agents such as curcumin, resveratrol, genistein, epigallocatechin-3-gallate, indole-3-carbinol, and 3,3′-diindolylmethane exert their antiproliferative and/or proapoptotic effects through the regulation of one or more miRNAs. Therefore, this review will look at the regulation of miRNAs by natural agents as a means to potentially enhance the efficacy of conventional chemotherapy through combinatorial therapies. It is hoped that this would provide new strategies in cancer therapies to improve overall response and survival outcome in cancer patients.

  12. MicroRNA-17~92 inhibits colorectal cancer progression by targeting angiogenesis.

    Science.gov (United States)

    Ma, Huabin; Pan, Jin-Shui; Jin, Li-Xin; Wu, Jianfeng; Ren, Yan-Dan; Chen, Pengda; Xiao, Changchun; Han, Jiahuai

    2016-07-01

    The miR-17~92 microRNA (miRNA) cluster host gene is upregulated in a broad spectrum of human cancers including colorectal cancer (CRC). Previous studies have shown that miR-17~92 promotes tumorigenesis and cancer angiogenesis in some tumor models. However, its role in the initiation and progression of CRC remains unknown. In this study, we found that transgenic mice overexpressing miR-17~92 specifically in epithelial cells of the small and large intestines exhibited decreased tumor size and tumor angiogenesis in azoxymethane and dextran sulfate sodium salt (AOM-DSS)-induced CRC model as compared to their littermates control. Further study showed that miR-17~92 inhibited the progression of CRC via suppressing tumor angiogenesis through targeting multiple tumor angiogenesis-inducing genes, TGFBR2, HIF1α, and VEGFA in vivo and in vitro. Collectively, we demonstrated that miR-17~92 suppressed tumor progression by inhibiting tumor angiogenesis in a genetically engineered mouse model, indicating the presence of cellular context-dependent pro- and anti-cancer effects of miR-17~92. PMID:27080303

  13. Action Mechanisms of MicroRNAs in Gastric Cancer and its Application in Translational Medicine

    Directory of Open Access Journals (Sweden)

    Xin-en HUANG

    2015-09-01

    Full Text Available Translational medicine is a new concept proposed in the field of international medicine and emphasizes a two-sided way from bench to beside and from beside to bench. Gastric cancer is a commonly encountered malignant tumor in the digestive system all over the world, with high morbidity and mortality. Although its incidence is decreasing, the outcomes of this disease are among the poorest in all solid tumors. Therefore, it is very urgent to seek new preventive and therapeutic targets for gastric cancer and to make basic research results apply in clinic. MicroRNAs (miRNAs are a classification of endogenous non-coding RNA with the function of regulating the expression of target genes. More and more studies have revealed that miRNAs are intimately associated with the occurrence, development, treatment and prognosis of gastric cancer. Therefore, this review provides an overview of the effects of miRNAs in gastric cancer on the cell cycle, apoptosis, invasion, metastasis, radiosensitivity and chemosensitivity.

  14. Salivary microRNAs as promising biomarkers for detection of esophageal cancer.

    Directory of Open Access Journals (Sweden)

    Zijun Xie

    Full Text Available BACKGROUND AND PURPOSE: Tissue microRNAs (miRNAs can detect cancers and predict prognosis. Several recent studies reported that tissue, plasma, and saliva miRNAs share similar expression profiles. In this study, we investigated the discriminatory power of salivary miRNAs (including whole saliva and saliva supernatant for detection of esophageal cancer. MATERIALS AND METHODS: By Agilent microarray, six deregulated miRNAs from whole saliva samples from seven patients with esophageal cancer and three healthy controls were selected. The six selected miRNAs were subjected to validation of their expression levels by RT-qPCR using both whole saliva and saliva supernatant samples from an independent set of 39 patients with esophageal cancer and 19 healthy controls. RESULTS: Six miRNAs (miR-10b*, miR-144, miR-21, miR-451, miR-486-5p, and miR-634 were identified as targets by Agilent microarray. After validation by RT-qPCR, miR-10b*, miR-144, and miR-451 in whole saliva and miR-10b*, miR-144, miR-21, and miR-451 in saliva supernatant were significantly upregulated in patients, with sensitivities of 89.7, 92.3, 84.6, 79.5, 43.6, 89.7, and 51.3% and specificities of 57.9, 47.4, 57.9%, 57.9, 89.5, 47.4, and 84.2%, respectively. CONCLUSIONS: We found distinctive miRNAs for esophageal cancer in both whole saliva and saliva supernatant. These miRNAs possess discriminatory power for detection of esophageal cancer. Because saliva collection is noninvasive and convenient, salivary miRNAs show great promise as biomarkers for detection of esophageal cancer in areas at high risk.

  15. MicroRNA-375 inhibits colorectal cancer growth by targeting PIK3CA

    International Nuclear Information System (INIS)

    Highlights: • miR-375 is downregulated in colorectal cancer cell lines and tissues. • miR-375 inhibits colorectal cancer cell growth by targeting PIK3CA. • miR-375 inhibits colorectal cancer cell growth in xenograft nude mice model. - Abstract: Colorectal cancer (CRC) is the second most common cause of death from cancer. MicroRNAs (miRNAs) represent a class of small non-coding RNAs that control gene expression by triggering RNA degradation or interfering with translation. Aberrant miRNA expression is involved in human disease including cancer. Herein, we showed that miR-375 was frequently down-regulated in human colorectal cancer cell lines and tissues when compared to normal human colon tissues. PIK3CA was identified as a potential miR-375 target by bioinformatics. Overexpression of miR-375 in SW480 and HCT15 cells reduced PIK3CA protein expression. Subsequently, using reporter constructs, we showed that the PIK3CA untranslated region (3′-UTR) carries the directly binding site of miR-375. Additionally, miR-375 suppressed CRC cell proliferation and colony formation and led to cell cycle arrest. Furthermore, miR-375 overexpression resulted in inhibition of phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway. SiRNA-mediated silencing of PIK3CA blocked the inhibitory effect of miR-375 on CRC cell growth. Lastly, we found overexpressed miR-375 effectively repressed tumor growth in xenograft animal experiments. Taken together, we propose that overexpression of miR-375 may provide a selective growth inhibition for CRC cells by targeting PI3K/Akt signaling pathway

  16. MicroRNA-375 inhibits colorectal cancer growth by targeting PIK3CA

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Yihui [Department of Colorectal Surgery, The Third Affiliated Hospital of Harbin Medical University, 150 Haping Road, 150081 Harbin (China); Tang, Qingchao [Cancer Center, The Second Affiliated Hospital of Harbin Medical University, 246 Xuefu Road, 150086 Harbin (China); Li, Mingqi; Jiang, Shixiong [Department of Colorectal Surgery, The Third Affiliated Hospital of Harbin Medical University, 150 Haping Road, 150081 Harbin (China); Wang, Xishan, E-mail: wxshan12081@163.com [Cancer Center, The Second Affiliated Hospital of Harbin Medical University, 246 Xuefu Road, 150086 Harbin (China)

    2014-02-07

    Highlights: • miR-375 is downregulated in colorectal cancer cell lines and tissues. • miR-375 inhibits colorectal cancer cell growth by targeting PIK3CA. • miR-375 inhibits colorectal cancer cell growth in xenograft nude mice model. - Abstract: Colorectal cancer (CRC) is the second most common cause of death from cancer. MicroRNAs (miRNAs) represent a class of small non-coding RNAs that control gene expression by triggering RNA degradation or interfering with translation. Aberrant miRNA expression is involved in human disease including cancer. Herein, we showed that miR-375 was frequently down-regulated in human colorectal cancer cell lines and tissues when compared to normal human colon tissues. PIK3CA was identified as a potential miR-375 target by bioinformatics. Overexpression of miR-375 in SW480 and HCT15 cells reduced PIK3CA protein expression. Subsequently, using reporter constructs, we showed that the PIK3CA untranslated region (3′-UTR) carries the directly binding site of miR-375. Additionally, miR-375 suppressed CRC cell proliferation and colony formation and led to cell cycle arrest. Furthermore, miR-375 overexpression resulted in inhibition of phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway. SiRNA-mediated silencing of PIK3CA blocked the inhibitory effect of miR-375 on CRC cell growth. Lastly, we found overexpressed miR-375 effectively repressed tumor growth in xenograft animal experiments. Taken together, we propose that overexpression of miR-375 may provide a selective growth inhibition for CRC cells by targeting PI3K/Akt signaling pathway.

  17. MicroRNA hsa-miR-4674 in Hemolysis-Free Blood Plasma Is Associated with Distant Metastases of Prostatic Cancer.

    Science.gov (United States)

    Knyazev, E N; Samatov, T R; Fomicheva, K A; Nyushko, K M; Alekseev, B Ya; Shkurnikov, M Yu

    2016-05-01

    We analyzed microRNA profile in hemolysis-free blood plasma of patients with prostatic cancer. The metastatic form of prostatic cancer was found to be associated with increased levels of hsa-miR-22-3p, hsa-miR-663a, and hsa-miR-4674 in comparison with non-metastatic form. Common candidate target genes of these microRNA include JUNB, KMT2A, and XPO6. PMID:27265126

  18. Research Networks Map | Division of Cancer Prevention

    Science.gov (United States)

    The Division of Cancer Prevention supports major scientific collaborations and research networks at more than 100 sites across the United States.  Five Major Programs' sites are shown on this map. | The Division of Cancer Prevention supports major scientific collaborations and research networks at more than 100 sites across the United States.

  19. Matrigel Basement Membrane Matrix influences expression of microRNAs in cancer cell lines

    International Nuclear Information System (INIS)

    Highlights: ► Matrigel alters cancer cell line miRNA expression relative to culture on plastic. ► Many identified Matrigel-regulated miRNAs are implicated in cancer. ► miR-1290, -210, -32 and -29b represent a Matrigel-induced miRNA signature. ► miR-32 down-regulates Integrin alpha 5 (ITGA5) mRNA. -- Abstract: Matrigel is a medium rich in extracellular matrix (ECM) components used for three-dimensional cell culture and is known to alter cellular phenotypes and gene expression. microRNAs (miRNAs) are small, non-coding RNAs that regulate gene expression and have roles in cancer. While miRNA profiles of numerous cell lines cultured on plastic have been reported, the influence of Matrigel-based culture on cancer cell miRNA expression is largely unknown. This study investigated the influence of Matrigel on the expression of miRNAs that might facilitate ECM-associated cancer cell growth. We performed miRNA profiling by microarray using two colon cancer cell lines (SW480 and SW620), identifying significant differential expression of miRNAs between cells cultured in Matrigel and on plastic. Many of these miRNAs have previously been implicated in cancer-related processes. A common Matrigel-induced miRNA signature comprised of up-regulated miR-1290 and miR-210 and down-regulated miR-29b and miR-32 was identified using RT-qPCR across five epithelial cancer cell lines (SW480, SW620, HT-29, A549 and MDA-MB-231). Experimental modulation of these miRNAs altered expression of their known target mRNAs involved in cell adhesion, proliferation and invasion, in colon cancer cell lines. Furthermore, ITGA5 was identified as a novel putative target of miR-32 that may facilitate cancer cell interactions with the ECM. We propose that culture of cancer cell lines in Matrigel more accurately recapitulates miRNA expression and function in cancer than culture on plastic and thus is a valuable approach to the in vitro study of miRNAs.

  20. Matrigel Basement Membrane Matrix influences expression of microRNAs in cancer cell lines

    Energy Technology Data Exchange (ETDEWEB)

    Price, Karina J. [Laboratory for Cancer Medicine, Western Australian Institute for Medical Research and University of Western Australia Centre for Medical Research, Perth, WA 6000 (Australia); School of Medicine and Pharmacology, University of Western Australia, Nedlands, WA 6008 (Australia); Tsykin, Anna [Centre for Cancer Biology, SA Pathology, Adelaide, SA 5000 (Australia); School of Molecular and Biomedical Science, University of Adelaide, Adelaide, SA 5005 (Australia); Giles, Keith M. [Laboratory for Cancer Medicine, Western Australian Institute for Medical Research and University of Western Australia Centre for Medical Research, Perth, WA 6000 (Australia); Sladic, Rosemary T. [Centre for Cancer Biology, SA Pathology, Adelaide, SA 5000 (Australia); Epis, Michael R. [Laboratory for Cancer Medicine, Western Australian Institute for Medical Research and University of Western Australia Centre for Medical Research, Perth, WA 6000 (Australia); Ganss, Ruth [Laboratory for Cancer Medicine Angiogenesis Unit, Western Australian Institute for Medical Research and University of Western Australia Centre for Medical Research, Perth, WA 6000 (Australia); Goodall, Gregory J. [Centre for Cancer Biology, SA Pathology, Adelaide, SA 5000 (Australia); School of Molecular and Biomedical Science, University of Adelaide, Adelaide, SA 5005 (Australia); Department of Medicine, University of Adelaide, Adelaide, SA 5005 (Australia); Leedman, Peter J., E-mail: peter.leedman@waimr.uwa.edu.au [Laboratory for Cancer Medicine, Western Australian Institute for Medical Research and University of Western Australia Centre for Medical Research, Perth, WA 6000 (Australia); School of Medicine and Pharmacology, University of Western Australia, Nedlands, WA 6008 (Australia)

    2012-10-19

    Highlights: Black-Right-Pointing-Pointer Matrigel alters cancer cell line miRNA expression relative to culture on plastic. Black-Right-Pointing-Pointer Many identified Matrigel-regulated miRNAs are implicated in cancer. Black-Right-Pointing-Pointer miR-1290, -210, -32 and -29b represent a Matrigel-induced miRNA signature. Black-Right-Pointing-Pointer miR-32 down-regulates Integrin alpha 5 (ITGA5) mRNA. -- Abstract: Matrigel is a medium rich in extracellular matrix (ECM) components used for three-dimensional cell culture and is known to alter cellular phenotypes and gene expression. microRNAs (miRNAs) are small, non-coding RNAs that regulate gene expression and have roles in cancer. While miRNA profiles of numerous cell lines cultured on plastic have been reported, the influence of Matrigel-based culture on cancer cell miRNA expression is largely unknown. This study investigated the influence of Matrigel on the expression of miRNAs that might facilitate ECM-associated cancer cell growth. We performed miRNA profiling by microarray using two colon cancer cell lines (SW480 and SW620), identifying significant differential expression of miRNAs between cells cultured in Matrigel and on plastic. Many of these miRNAs have previously been implicated in cancer-related processes. A common Matrigel-induced miRNA signature comprised of up-regulated miR-1290 and miR-210 and down-regulated miR-29b and miR-32 was identified using RT-qPCR across five epithelial cancer cell lines (SW480, SW620, HT-29, A549 and MDA-MB-231). Experimental modulation of these miRNAs altered expression of their known target mRNAs involved in cell adhesion, proliferation and invasion, in colon cancer cell lines. Furthermore, ITGA5 was identified as a novel putative target of miR-32 that may facilitate cancer cell interactions with the ECM. We propose that culture of cancer cell lines in Matrigel more accurately recapitulates miRNA expression and function in cancer than culture on plastic and thus is a

  1. MicroRNA-125b Induces Cancer Cell Apoptosis Through Suppression of Bcl-2 Expression

    Institute of Scientific and Technical Information of China (English)

    Aihua Zhao; Quan Zeng; Xiaoyan Xie; unnian Zhou; Wen Yue; Yali Li; Xuetao Pei

    2012-01-01

    MicroRNAs (miRNAs) are small,noncoding RNAs which can often act as an oncogene or a tumor suppressor.Several miRNAs are associated with the development of hepatocellular carcinoma (HCC).We demonstrated that miR-125b significantly suppresses HCC cell proliferation and promotes apoptosis by inhibiting the gene expression of the anti-apoptotic protein,Bcl-2.Bioinformatic analysis indicated that the 3'UTR of Bcl-2 has binding sites for miR-125b.Luciferase reporter assay confirmed the ability of miR-125b to dramatically suppress Bcl-2 transcription,suggesting that Bcl-2 is a target gene for miR-125b.We concluded that miR-125b acts as a tumor suppressor in hepatic tumor development by targeting Bcl-2 and inducing cancer cell apoptosis.

  2. Clinical implications of microRNAs in liver cancer stem cells

    Institute of Scientific and Technical Information of China (English)

    Stella Chai; Stephanie Ma

    2013-01-01

    The prognosis of patients diagnosed with hepatocellular carcinoma (HCC) is often dismal,mainly due to late presentation,high recurrence rate,and frequent resistance to chemotherapy and radiotherapy.Accumulating evidence on the differential microRNA (miRNA) expression patterns between non-tumor and HCC tissues or between liver cancer stem cells (CSCs) and non-CSC subsets and the significant clinical implications of these differences suggest that miRNAs are a promising,non-invasive marker for the prognosis and diagnosis of the disease.This perspective article summarizes the current knowledge of miRNAs in liver CSCs and highlights the need for further investigations of the role of miRNAs in regulating liver CSC subsets for possible future clinical applications.

  3. The potential diagnostic value of serum microRNA signature in patients with pancreatic cancer

    DEFF Research Database (Denmark)

    Johansen, Julia S; Calatayud, Dan; Albieri, Vanna;

    2016-01-01

    Biomarkers for early diagnosis of patients with pancreatic cancer (PC) are needed. Our aim was to identify panels of miRNAs in serum in combination with CA 19-9 for use in the diagnosis of PC. Four hundred seventeen patients with PC were included prospectively from Denmark (n = 306) and Germany (n...... = 111). Controls included 59 patients with chronic pancreatitis (CP) and 248 healthy subjects (HS). MiRNAs were analyzed in pretreatment serum samples from 3 cohorts: discovery cohort (754 human miRNAs, TaqMan(®) Human MicroRNA assay, Applied Biosystem; PC n = 133, controls n = 72); training cohort (34...

  4. Optimized high-throughput microRNA expression profiling provides novel biomarker assessment of clinical prostate and breast cancer biopsies

    Directory of Open Access Journals (Sweden)

    Fedele Vita

    2006-06-01

    Full Text Available Abstract Background Recent studies indicate that microRNAs (miRNAs are mechanistically involved in the development of various human malignancies, suggesting that they represent a promising new class of cancer biomarkers. However, previously reported methods for measuring miRNA expression consume large amounts of tissue, prohibiting high-throughput miRNA profiling from typically small clinical samples such as excision or core needle biopsies of breast or prostate cancer. Here we describe a novel combination of linear amplification and labeling of miRNA for highly sensitive expression microarray profiling requiring only picogram quantities of purified microRNA. Results Comparison of microarray and qRT-PCR measured miRNA levels from two different prostate cancer cell lines showed concordance between the two platforms (Pearson correlation R2 = 0.81; and extension of the amplification, labeling and microarray platform was successfully demonstrated using clinical core and excision biopsy samples from breast and prostate cancer patients. Unsupervised clustering analysis of the prostate biopsy microarrays separated advanced and metastatic prostate cancers from pooled normal prostatic samples and from a non-malignant precursor lesion. Unsupervised clustering of the breast cancer microarrays significantly distinguished ErbB2-positive/ER-negative, ErbB2-positive/ER-positive, and ErbB2-negative/ER-positive breast cancer phenotypes (Fisher exact test, p = 0.03; as well, supervised analysis of these microarray profiles identified distinct miRNA subsets distinguishing ErbB2-positive from ErbB2-negative and ER-positive from ER-negative breast cancers, independent of other clinically important parameters (patient age; tumor size, node status and proliferation index. Conclusion In sum, these findings demonstrate that optimized high-throughput microRNA expression profiling offers novel biomarker identification from typically small clinical samples such as breast

  5. MicroRNAs and Lymph Node Metastasis in Papillary Thyroid Cancers.

    Science.gov (United States)

    Mutalib, Nurul-Syakima Ab; Yusof, Azliana Mohamad; Mokhtar, Norfilza Mohd; Harun, Roslan; Muhammad, Rohaizak; Jamal, Rahman

    2016-01-01

    Lymph node metastasis (LNM) in papillary thyroid cancer (PTC) has been shown to be associated with increased risk of locoregional recurrence, poor prognosis and decreased survival, especially in older patients. Hence, there is a need for a reliable biomarker for the prediction of LNM in this cancer. MicroRNAs (miRNAs) are small noncoding RNAs that regulate gene translation or degradation and play key roles in numerous cellular functions including cell-cycle regulation, differentiation, apoptosis, invasion and migration. Various studies have demonstrated deregulation of miRNA levels in many diseases including cancers. While a large number of miRNAs have been identified from PTCs using various means, association of miRNAs with LNM in such cases is still controversial. Furthermore, studies linking most of the identified miRNAs to the mechanism of LNM have not been well documented. The aim of this review is to update readers on the current knowledge of miRNAs in relation to LNM in PTC. PMID:26838219

  6. Overlapping expression of microRNAs in human embryonic colon and colorectal cancer

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    MicroRNAs (miRNAs) are essential for regulating cell differentiation and maintaining the pluripotent state of stem cells. Although dysregulation of specific miRNAs has been associated with certain types of cancer, to date no evidence has linked miRNA expression in embryonic and tumor tissues. We assessed the expression of mature miRNAs in human embryonic colon tissue, and in colorectal cancer and paired normal colon tissue. Overlapping miRNA expression was detected between embryonic colonic mucosa and colorectal cancer. We have found that the miR-17-92 cluster and its target, E2F1, exhibit a similar pattern of expression in human colon development and colonic carcinogenesis, regulating cell proliferation in both cases. In situ hybridization confirmed the high level of expression of miR-17-5p in the crypt progenitor compartment. We conclude that miRNA pathways play a major role in both embryonic development and neoplastic transformation of the colonic epithelium.

  7. MicroRNA Expression in Formalin-fixed Paraffin-embedded Cancer Tissue

    DEFF Research Database (Denmark)

    Boisen, Mogens Karsbøl; Dehlendorff, Christian; Linnemann, Dorte;

    2015-01-01

    BACKGROUND: Archival formalin-fixed paraffin-embedded (FFPE) cancer tissue samples are a readily available resource for microRNA (miRNA) biomarker identification. No established standard for reference miRNAs in FFPE tissue exists. We sought to identify stable reference miRNAs for normalization of...... miRNA expression in FFPE tissue samples from patients with colorectal (CRC) and pancreatic (PC) cancer and to quantify the variability associated with sample age and fixation. METHODS: High-throughput miRNA profiling results from 203 CRC and 256 PC FFPE samples as well as from 37 paired frozen...... global mean expression in each cancer type. Nine of these miRNAs were present in both lists, and miR-103a-3p was the most stable reference miRNA for both CRC and PC FFPE tissue. The optimal number of reference miRNAs was 4 in CRC and 10 in PC. Sample age had a significant effect on global mi...

  8. MicroRNA dysregulation as a prognostic biomarker in colorectal cancer

    International Nuclear Information System (INIS)

    Colorectal cancer (CRC) is one of the most potentially curable cancers, yet it remains the fourth most common overall cause of cancer death worldwide. The identification of robust molecular prognostic biomarkers can refine the conventional tumor–node–metastasis staging system, avoid understaging of tumor, and help pinpoint patients with early-stage CRC who may benefit from aggressive treatments. Recently, epigenetic studies have provided new molecular evidence to better categorize the CRC subtypes and predict clinical outcomes. In this review, we summarize recent findings concerning the prognostic potential of microRNAs (miRNAs) in CRC. We first discuss the prognostic value of three tissue miRNAs (miR-21-5p, miR-29-3p, miR-148-3p) that have been examined in multiple studies. We also summarize the dysregulation of miRNA processing machinery DICER in CRC and its association with risk for mortality. We also reviewe the potential application of miRNA-associated single-nucleotide polymorphisms as prognostic biomarkers for CRC, especially the miRNA-associated polymorphism in the KRAS gene. Last but not least, we discuss the microsatellite instability-related miRNA candidates. Among all these candidates, miR-21-5p is the most promising prognostic marker, yet further prospective validation studies are required before it can go into clinical usage

  9. Recent progress in microRNA delivery for cancer therapy by non-viral synthetic vectors.

    Science.gov (United States)

    Wang, Huiyuan; Jiang, Yifan; Peng, Huige; Chen, Yingzhi; Zhu, Peizhi; Huang, Yongzhuo

    2015-01-01

    MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression. Because of significant changes in their expression in cancer, miRNAs are believed to be key factors in cancer genetics and to have potential as anticancer drugs. However, the delivery of miRNAs is limited by many barriers, such as low cellular uptake, immunogenicity, renal clearance, degradation by nucleases, elimination by phagocytic immune cells, poor endosomal release, and untoward side effects. Nonviral delivery systems have been developed to overcome these obstacles. In this review, we provide insights into the development of non-viral synthetic miRNA vectors and the promise of miRNA-based anticancer therapies, including therapeutic applications of miRNAs, challenges of vector design to overcome the delivery obstacles, and the development of miRNA delivery systems for cancer therapy. Additionally, we highlight some representative examples that give a glimpse into the current trends into the design and application of efficient synthetic systems for miRNA delivery. Overall, a better understanding of the rational design of miRNA delivery systems will promote their translation into effective clinical treatments. PMID:25450259

  10. Loss of microRNA-27b contributes to breast cancer stem cell generation by activating ENPP1

    OpenAIRE

    Takahashi, Ryou-u; Miyazaki, Hiroaki; Takeshita, Fumitaka; Yamamoto, Yusuke; Minoura, Kaho; Ono, Makiko; Kodaira, Makoto; Tamura, Kenji; MORI, MASAKI; Ochiya, Takahiro

    2015-01-01

    Cancer stem cells (CSCs) have been identified in various types of cancer; however, the mechanisms by which cells acquire CSC properties such as drug resistance and tumour seeding ability are not fully understood. Here, we identified microRNA-27b (miR-27b) as a key regulator for the generation of a side-population in breast cancer cells that showed CSC properties, and also found that the anti-type II diabetes (T2D) drug metformin reduced this side-population via miR-27b-mediated repression of ...

  11. The expression and function of microRNA-203 in lung cancer.

    Science.gov (United States)

    Jin, Jianhua; Deng, Jianzhong; Wang, Fang; Xia, Xiyi; Qiu, Tiefeng; Lu, Wenbin; Li, Xianwen; Zhang, Hua; Gu, Xiaoyan; Liu, Yungang; Cao, Weiguo; Shao, Wenlong

    2013-02-01

    We aimed to determine the expression of microRNA-203 (miR-203) in human lung cancer cell lines and to evaluate the effects of miR-203 by targeting survivin, on the lung cancer cell line 95-D to provide potential new strategies for treating lung cancer. The expression of miR-203 was detected using quantitative real-time PCR (qRT-PCR) in the in vitro cultured lung cancer cells A549, HCC827, NCI-H1299, and 95-D as well as in normal human bronchial epithelial cells. Following a 72-h transfection with the miR-203 precursor in 95-D lung cancer cells, the change in miR-203 expression was detected using qRT-PCR and the resulting effect on survivin protein expression was ascertained by Western blot analysis. The influence of miR-203 on the viability of 95-D lung cancer cells was evaluated using 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. The effect of miR-203 on 95-D cell proliferation was analyzed using flow cytometry. The consequences of miR-203 expression on 95-D cell apoptosis were analyzed by Annexin V/propidium iodide double staining coupled with flow cytometry. The role of miR-203 in the invasive potential of 95-D cells was studied using a transwell chamber assay. A luciferase reporter gene system was used to verify that survivin is a target gene for miR-203. By qRT-PCR, the expression of miR-203 was lower in lung cancer cells than in normal bronchial epithelial cells (p transfection with the miR-203 precursor (p transfection with the miR-203 precursor, survivin protein levels in 95-D cells were significantly decreased (p transfection with the miR-203 precursor (p < 0.05). The expression of miR-203 is downregulated in lung cancer cells. miR-203 negatively regulates survivin protein expression and inhibits the proliferation and invasion of lung cancer cells. Therapeutic strategies that enhance miR-203 expression or silence survivin could potentially benefit lung cancer patients. PMID:23073851

  12. Bioinformatic analysis of microRNA networks following the activation of the constitutive androstane receptor (CAR) in mouse liver.

    Science.gov (United States)

    Hao, Ruixin; Su, Shengzhong; Wan, Yinan; Shen, Frank; Niu, Ben; Coslo, Denise M; Albert, Istvan; Han, Xing; Omiecinski, Curtis J

    2016-09-01

    The constitutive androstane receptor (CAR; NR1I3) is a member of the nuclear receptor superfamily that functions as a xenosensor, serving to regulate xenobiotic detoxification, lipid homeostasis and energy metabolism. CAR activation is also a key contributor to the development of chemical hepatocarcinogenesis in mice. The underlying pathways affected by CAR in these processes are complex and not fully elucidated. MicroRNAs (miRNAs) have emerged as critical modulators of gene expression and appear to impact many cellular pathways, including those involved in chemical detoxification and liver tumor development. In this study, we used deep sequencing approaches with an Illumina HiSeq platform to differentially profile microRNA expression patterns in livers from wild type C57BL/6J mice following CAR activation with the mouse CAR-specific ligand activator, 1,4-bis-[2-(3,5,-dichloropyridyloxy)] benzene (TCPOBOP). Bioinformatic analyses and pathway evaluations were performed leading to the identification of 51 miRNAs whose expression levels were significantly altered by TCPOBOP treatment, including mmu-miR-802-5p and miR-485-3p. Ingenuity Pathway Analysis of the differentially expressed microRNAs revealed altered effector pathways, including those involved in liver cell growth and proliferation. A functional network among CAR targeted genes and the affected microRNAs was constructed to illustrate how CAR modulation of microRNA expression may potentially mediate its biological role in mouse hepatocyte proliferation. This article is part of a Special Issue entitled: Xenobiotic nuclear receptors: New Tricks for An Old Dog, edited by Dr. Wen Xie. PMID:27080131

  13. MicroRNA-135b promotes cancer progression by acting as a downstream effector of oncogenic pathways in colon cancer.

    Science.gov (United States)

    Valeri, Nicola; Braconi, Chiara; Gasparini, Pierluigi; Murgia, Claudio; Lampis, Andrea; Paulus-Hock, Viola; Hart, Jonathan R; Ueno, Lynn; Grivennikov, Sergei I; Lovat, Francesca; Paone, Alessio; Cascione, Luciano; Sumani, Khlea M; Veronese, Angelo; Fabbri, Muller; Carasi, Stefania; Alder, Hansjuerg; Lanza, Giovanni; Gafa', Roberta; Moyer, Mary P; Ridgway, Rachel A; Cordero, Julia; Nuovo, Gerard J; Frankel, Wendy L; Rugge, Massimo; Fassan, Matteo; Groden, Joanna; Vogt, Peter K; Karin, Michael; Sansom, Owen J; Croce, Carlo M

    2014-04-14

    MicroRNA deregulation is frequent in human colorectal cancers (CRCs), but little is known as to whether it represents a bystander event or actually drives tumor progression in vivo. We show that miR-135b overexpression is triggered in mice and humans by APC loss, PTEN/PI3K pathway deregulation, and SRC overexpression and promotes tumor transformation and progression. We show that miR-135b upregulation is common in sporadic and inflammatory bowel disease-associated human CRCs and correlates with tumor stage and poor clinical outcome. Inhibition of miR-135b in CRC mouse models reduces tumor growth by controlling genes involved in proliferation, invasion, and apoptosis. We identify miR-135b as a key downsteam effector of oncogenic pathways and a potential target for CRC treatment. PMID:24735923

  14. MicroRNA analysis of breast ductal fluid in breast cancer patients.

    Science.gov (United States)

    Do Canto, Luisa Matos; Marian, Catalin; Willey, Shawna; Sidawy, Mary; Da Cunha, Patricia A; Rone, Janice D; Li, Xin; Gusev, Yuriy; Haddad, Bassem R

    2016-05-01

    Recent studies suggest that microRNAs show promise as excellent biomarkers for breast cancer; however there is still a high degree of variability between studies making the findings difficult to interpret. In addition to blood, ductal lavage (DL) and nipple aspirate fluids represent an excellent opportunity for biomarker detection because they can be obtained in a less invasive manner than biopsies and circumvent the limitations of evaluating blood biomarkers with regards to tissue of origin specificity. In this study, we have investigated for the first time, through a real-time PCR array, the expression of 742 miRNAs in the ductal lavage fluid collected from 22 women with unilateral breast tumors. We identified 17 differentially expressed miRNAs between tumor and paired normal samples from patients with ductal breast carcinoma. Most of these miRNAs have various roles in breast cancer tumorigenesis, invasion and metastasis, therapeutic response, or are associated with several clinical and pathological characteristics of breast tumors. Moreover, some miRNAs were also detected in other biological fluids of breast cancer patients such as serum (miR-23b, -133b, -181a, 338-3p, -625), plasma (miR-200a), and breast milk (miR-181a). A systems biology analysis of these differentially expressed miRNAs points out possible pathways and cellular processes previously described as having an important role in breast cancer such as Wnt, ErbB, MAPK, TGF-β, mTOR, PI3K-Akt, p53 signaling pathways. We also observed a difference in the miRNA expression with respect to the histological type of the tumors. In conclusion, our findings suggest that miRNA analysis of breast ductal fluid is feasible and potentially very useful for the detection of breast cancer. PMID:26984519

  15. Clinical relevance of circulating cell-free microRNAs in ovarian cancer.

    Science.gov (United States)

    Nakamura, Koji; Sawada, Kenjiro; Yoshimura, Akihiko; Kinose, Yasuto; Nakatsuka, Erika; Kimura, Tadashi

    2016-01-01

    Ovarian cancer is the leading cause of death among gynecologic malignancies. Since ovarian cancer develops asymptomatically, it is often diagnosed at an advanced and incurable stage. Despite many years of research, there is still a lack of reliable diagnostic markers and methods for early detection and screening. Recently, it was discovered that cell-free microRNAs (miRNAs) circulate in the body fluids of healthy and diseased patients, suggesting that they may serve as a novel diagnostic marker. This review summarizes the current knowledge regarding the potential clinical relevance of circulating cell-free miRNA for ovarian cancer diagnosis, prognosis, and therapeutics. Despite the high levels of ribonucleases in many types of body fluids, most of the circulating miRNAs are packaged in microvesicles, exosomes, or apoptotic bodies, are binding to RNA-binding protein such as argonaute 2 or lipoprotein complexes, and are thus highly stable. Cell-free miRNA signatures are known to be parallel to those from the originating tumor cells, indicating that circulating miRNA profiles accurately reflect the tumor profiles. Since it is well established that the dysregulation of miRNAs is involved in the tumorigenesis of ovarian cancer, cell-free miRNAs circulating in body fluids such as serum, plasma, whole blood, and urine may reflect not only the existence of ovarian cancer but also tumor histology, stage, and prognoses of the patients. Several groups have successfully demonstrated that serum or plasma miRNAs are able to discriminate patients with ovarian cancer patients from healthy controls, suggesting that the addition of these miRNAs to current testing regimens may improve diagnosis accuracies for ovarian cancer. Furthermore, recent studies have revealed that changes in levels of cell-free circulating miRNAs are associated with the condition of cancer patients. Discrepancies between the results across studies due to the lack of an established endogenous miRNA control to

  16. MicroRNA-200 Family Profile: A Promising Ancillary Tool for Accurate Cancer Diagnosis.

    Science.gov (United States)

    Liu, Xiaodong; Zhang, Jianhua; Xie, Botao; Li, Hao; Shen, Jihong; Chen, Jianheng

    2016-01-01

    Cancer is one of the most threatening diseases in the world and great interests have been paid to discover accurate and noninvasive methods for cancer diagnosis. The value of microRNA-200 (miRNA-200, miR-200) family has been revealed in many studies. However, the results from various studies were inconsistent, and thus a meta-analysis was designed and performed to assess the overall value of miRNA200 in cancer diagnosis. Relevant studies were searched electronically from the following databases: PubMed, Embase, Web of Science, the Cochrane Library, and Chinese National Knowledge Infrastructure. Keyword combined with "miR-200," "cancer," and "diagnosis" in any fields was used for searching relevant studies. Then, the pooled sensitivity, specificity, area under the curve (AUC), and partial AUC were calculated using the random-effects model. Heterogeneity among individual studies was also explored by subgroup analyses. A total of 28 studies from 18 articles with an overall sample size of 3676 subjects (2097 patients and 1579 controls) were included in this meta-analysis. The overall sensitivity and specificity with 95% confidence intervals (95% CIs) are 0.709 (95% CI: 0.657-0.755) and 0.667 (95% CI: 0.617-0.713), respectively. Additionally, AUC and partial AUC for the pooled data is 0.735 and 0.627, respectively. Subgroup analyses revealed that using miRNA-200 family for cancer diagnosis is more effective in white than in Asian ethnic groups. In addition, cancer diagnosis by miRNA using circulating specimen is more effective than that using noncirculating specimen. Finally, miRNA is more accurate in diagnosing endometrial cancer than other types of cancer, and some miRNA family members (miR-200b and miR-429) have superior diagnostic accuracy than other miR-200 family members. In conclusion, the profiling of miRNA-200 family is likely to be a valuable tool in cancer detection and diagnosis. PMID:26618619

  17. An Extensive Network of TET2-Targeting MicroRNAs Regulates Malignant Hematopoiesis

    Directory of Open Access Journals (Sweden)

    Jijun Cheng

    2013-10-01

    Full Text Available The Ten-Eleven-Translocation 2 (TET2 gene, which oxidates 5-methylcytosine in DNA to 5-hydroxylmethylcytosine (5hmC, is a key tumor suppressor frequently mutated in hematopoietic malignancies. However, the molecular regulation of TET2 expression is poorly understood. We show that TET2 is under extensive microRNA (miRNA regulation, and such TET2 targeting is an important pathogenic mechanism in hematopoietic malignancies. Using a high-throughput 3′ UTR activity screen, we identify >30 miRNAs that inhibit TET2 expression and cellular 5hmC. Forced expression of TET2-targeting miRNAs in vivo disrupts normal hematopoiesis, leading to hematopoietic expansion and/or myeloid differentiation bias, whereas coexpression of TET2 corrects these phenotypes. Importantly, several TET2-targeting miRNAs, including miR-125b, miR-29b, miR-29c, miR-101, and miR-7, are preferentially overexpressed in TET2-wild-type acute myeloid leukemia. Our results demonstrate the extensive roles of miRNAs in functionally regulating TET2 and cellular 5hmC and reveal miRNAs with previously unrecognized oncogenic potential. Our work suggests that TET2-targeting miRNAs might be exploited in cancer diagnosis.

  18. MicroRNAs and their target gene networks in renal cell carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Redova, Martina; Svoboda, Marek [Masaryk Memorial Cancer Institute, Department of Comprehensive Cancer Care, Brno (Czech Republic); Slaby, Ondrej, E-mail: slaby@mou.cz [Masaryk Memorial Cancer Institute, Department of Comprehensive Cancer Care, Brno (Czech Republic); Central European Institute of Technology, Masaryk University, Brno (Czech Republic)

    2011-02-11

    Research highlights: {yields} MiRNAs are related to the processes of cell proliferation, apoptosis, angiogenesis, invasion, and metastasis in RCC. {yields} MiRNAs expression profiles are associated with several RCC-specific genetic alterations. {yields} It has been well documented that several miRNAs are downstream effector molecules of the HIF-induced hypoxia response. {yields} MiR-200 family is linked to epithelial-mesenchymal transition which is one of the most significant pathogenetic mechanism in RCC. {yields} Mechanistic studies in RCC have provided the rationale of using miRNAs as potential therapeutic targets. -- Abstract: MicroRNAs (miRNAs) are non-protein-coding short single stranded RNAs in the size range 19-25 nucleotides that are associated with gene regulation at the transcriptional and translational level. Recent studies have proved that miRNAs play important roles in a large number of biological processes, including cellular differentiation, proliferation, apoptosis, etc. Changes in their expression were found in a variety of human cancers, including renal cell carcinoma pathogenesis. Specific miRNA alterations were associated with key pathogenetic mechanisms of renal cell carcinoma like hypoxia or epithelial-mesenchymal transition. In this review, we summarize the current knowledge of miRNA functions in renal cell carcinoma with an emphasis on miRNAs potential to serve as a powerful biomarker of disease and a novel therapeutic target in oncology.

  19. MicroRNAs and their target gene networks in renal cell carcinoma

    International Nuclear Information System (INIS)

    Research highlights: → MiRNAs are related to the processes of cell proliferation, apoptosis, angiogenesis, invasion, and metastasis in RCC. → MiRNAs expression profiles are associated with several RCC-specific genetic alterations. → It has been well documented that several miRNAs are downstream effector molecules of the HIF-induced hypoxia response. → MiR-200 family is linked to epithelial-mesenchymal transition which is one of the most significant pathogenetic mechanism in RCC. → Mechanistic studies in RCC have provided the rationale of using miRNAs as potential therapeutic targets. -- Abstract: MicroRNAs (miRNAs) are non-protein-coding short single stranded RNAs in the size range 19-25 nucleotides that are associated with gene regulation at the transcriptional and translational level. Recent studies have proved that miRNAs play important roles in a large number of biological processes, including cellular differentiation, proliferation, apoptosis, etc. Changes in their expression were found in a variety of human cancers, including renal cell carcinoma pathogenesis. Specific miRNA alterations were associated with key pathogenetic mechanisms of renal cell carcinoma like hypoxia or epithelial-mesenchymal transition. In this review, we summarize the current knowledge of miRNA functions in renal cell carcinoma with an emphasis on miRNAs potential to serve as a powerful biomarker of disease and a novel therapeutic target in oncology.

  20. Assessment of diagnostic potency of exosomal microRNA in circulating blood of patient with thyroid cancer

    Directory of Open Access Journals (Sweden)

    R. B. Samsonov

    2015-11-01

    Full Text Available Diagnostics of thyroid cancer (TC remains a challenging issue due to the high incidence of asymptomatic thyroid nodular pathologies and absence of non-invasive methods of their assessment. Thyroid tumors are classified as benign and malignant with incidence ration approximated as 9:1. Correct and timely differential diagnosis is the basis for correctly choosing a treatment policy and hence determines treatment results. Methods for molecular genetic analysis are being recently developed and introduced into clinical practice, enabling the diagnostic process to be optimized. Analysis of the intracellular and secreted (exosomal fractions of small regulatory RNAs (microRNAs is one of the most promising methods for the diagnosis of cancers, including TC. The stability of extracellular microRNA is determined by bonds to proteins, lipoproteins, or its encapsulation into the membrane microvesicles – exosomes. There is reason for suggesting that exosomes with the specific composition of microRNA are a result of the process of active and biologically important secretion while release of other microRNA forms accompanies apoptotic or necrotic cell death. This determines the special diagnostic value of the exosomal fraction of circulating microRNAs, which may reflect the presence and clinically relevant properties of a tumor. This paper discusses the state of the problem and presents methods and preliminary results of the studies conducted by the authors to develop a novel method for diagnosing and monitoring TC. Thus, level of plasma exosomal miR-21 was shown to distinguish patients with benign tumor and follicular CT, while miR-31 can help to distinguish patients with benign tumor and papillary TC. Moreover, reciprocal character of miR-21 and miR-181a concentration in plasma exosomes was detected by comparison of patient with papillary and follicular TC.

  1. Overexpression of MicroRNA-30b Improves Adenovirus-Mediated p53 Cancer Gene Therapy for Laryngeal Carcinoma

    Directory of Open Access Journals (Sweden)

    Liang Li

    2014-10-01

    Full Text Available MicroRNAs play important roles in laryngeal carcinoma and other cancers. However, the expression of microRNAs in paracancerous tissue has been studied less. Here, using laser capture microdissection (LCM, we detected the expression of microRNAs in paracancerous tissues. Among all down-regulated microRNAs in the center area of tumor tissues, only miR-30b expression was significantly reduced in paracancerous tissues compared to surgical margins. Therefore, to further investigate the effect of miR-30b on laryngeal carcinoma, we stably overexpressed miR-30b in laryngeal carcinoma cell line HEp-2 cells. It was found that although there was no significant difference in cell viability between miR-30b overexpressed cells and control HEp-2 cells, p53 expression was obviously enhanced in miR-30b overexpressed cells. Whether miR-30b could improve the anti-tumor effect of adenovirus-p53 (Ad-p53 in laryngeal carcinoma and other cancer cell lines was also evaluated. It was found that in miR-30b overexpressed HEp-2 cells, p53-mediated tumor cell apoptosis was obviously increased both in vitro and in vivo. MDM2-p53 interaction might be involved in miR-30b-mediated anti-tumor effect. Together, results suggested that miR-30b could modulate p53 pathway and enhance p53 gene therapy-induced apoptosis in laryngeal carcinoma, which could provide a novel microRNA target in tumor therapy.

  2. Integration of hormonal signaling networks and mobile microRNAs is required for vascular patterning in Arabidopsis roots

    KAUST Repository

    Muraro, D.

    2013-12-31

    As multicellular organisms grow, positional information is continually needed to regulate the pattern in which cells are arranged. In the Arabidopsis root, most cell types are organized in a radially symmetric pattern; however, a symmetry-breaking event generates bisymmetric auxin and cytokinin signaling domains in the stele. Bidirectional cross-talk between the stele and the surrounding tissues involving a mobile transcription factor, SHORT ROOT (SHR), and mobile microRNA species also determines vascular pattern, but it is currently unclear how these signals integrate. We use a multicellular model to determine a minimal set of components necessary for maintaining a stable vascular pattern. Simulations perturbing the signaling network show that, in addition to the mutually inhibitory interaction between auxin and cytokinin, signaling through SHR, microRNA165/6, and PHABULOSA is required to maintain a stable bisymmetric pattern. We have verified this prediction by observing loss of bisymmetry in shr mutants. The model reveals the importance of several features of the network, namely the mutual degradation of microRNA165/6 and PHABULOSA and the existence of an additional negative regulator of cytokinin signaling. These components form a plausible mechanism capable of patterning vascular tissues in the absence of positional inputs provided by the transport of hormones from the shoot.

  3. Identification of microRNAs and mRNAs associated with multidrug resistance of human laryngeal cancer Hep-2 cells

    Energy Technology Data Exchange (ETDEWEB)

    Yin, Wanzhong; Wang, Ping; Wang, Xin [Department of Otorhinolaryngology, Head and Neck Surgery, The First Clinical Hospital, Norman Bethune College of Medicine, Jilin University, Changchun (China); Song, Wenzhi [Department of Stomatology, China-Japan Friendship Hospital, Jilin University, Changchun (China); Cui, Xiangyan; Yu, Hong; Zhu, Wei [Department of Otorhinolaryngology, Head and Neck Surgery, The First Clinical Hospital, Norman Bethune College of Medicine, Jilin University, Changchun (China)

    2013-06-12

    Multidrug resistance (MDR) poses a serious impediment to the success of chemotherapy for laryngeal cancer. To identify microRNAs and mRNAs associated with MDR of human laryngeal cancer Hep-2 cells, we developed a multidrug-resistant human laryngeal cancer subline, designated Hep-2/v, by exposing Hep-2 cells to stepwise increasing concentrations of vincristine (0.02-0.96'µM). Microarray assays were performed to compare the microRNA and mRNA expression profiles of Hep-2 and Hep-2/v cells. Compared to Hep-2 cells, Hep-2/v cells were more resistant to chemotherapy drugs (∼45-fold more resistant to vincristine, 5.1-fold more resistant to cisplatin, and 5.6-fold more resistant to 5-fluorouracil) and had a longer doubling time (42.33±1.76 vs 28.75±1.12'h, P<0.05), higher percentage of cells in G0/G1 phase (80.98±0.52 vs 69.14±0.89, P<0.05), increased efflux of rhodamine 123 (95.97±0.56 vs 12.40±0.44%, P<0.01), and up-regulated MDR1 expression. A total of 7 microRNAs and 605 mRNAs were differentially expressed between the two cell types. Of the differentially expressed mRNAs identified, regulator of G-protein signaling 10, high-temperature requirement protein A1, and nuclear protein 1 were found to be the putative targets of the differentially expressed microRNAs identified. These findings may open a new avenue for clarifying the mechanisms responsible for MDR in laryngeal cancer.

  4. Identification of microRNAs and mRNAs associated with multidrug resistance of human laryngeal cancer Hep-2 cells

    International Nuclear Information System (INIS)

    Multidrug resistance (MDR) poses a serious impediment to the success of chemotherapy for laryngeal cancer. To identify microRNAs and mRNAs associated with MDR of human laryngeal cancer Hep-2 cells, we developed a multidrug-resistant human laryngeal cancer subline, designated Hep-2/v, by exposing Hep-2 cells to stepwise increasing concentrations of vincristine (0.02-0.96'µM). Microarray assays were performed to compare the microRNA and mRNA expression profiles of Hep-2 and Hep-2/v cells. Compared to Hep-2 cells, Hep-2/v cells were more resistant to chemotherapy drugs (∼45-fold more resistant to vincristine, 5.1-fold more resistant to cisplatin, and 5.6-fold more resistant to 5-fluorouracil) and had a longer doubling time (42.33±1.76 vs 28.75±1.12'h, P<0.05), higher percentage of cells in G0/G1 phase (80.98±0.52 vs 69.14±0.89, P<0.05), increased efflux of rhodamine 123 (95.97±0.56 vs 12.40±0.44%, P<0.01), and up-regulated MDR1 expression. A total of 7 microRNAs and 605 mRNAs were differentially expressed between the two cell types. Of the differentially expressed mRNAs identified, regulator of G-protein signaling 10, high-temperature requirement protein A1, and nuclear protein 1 were found to be the putative targets of the differentially expressed microRNAs identified. These findings may open a new avenue for clarifying the mechanisms responsible for MDR in laryngeal cancer

  5. Identification of colorectal cancer-restricted microRNAs and their target genes based on high-throughput sequencing data

    OpenAIRE

    Chang J; Huang L; Cao Q; Liu F.

    2016-01-01

    Jing Chang, Liya Huang, Qing Cao, Fang Liu Department of Gerontology, Xinhua Hospital Affiliated to Jiaotong University School of Medicine, Shanghai, People’s Republic of China Abstract: To identify potential key microRNAs (miRNAs) and their target genes for colorectal cancer (CRC). High-throughput sequencing data of miRNA expression and gene expression (ID: GSE46622) were downloaded from Gene Expression Omnibus, including matched colon tumor, normal colon epithelium, and liver metast...

  6. Identification of colorectal cancer-restricted microRNAs and their target genes based on high-throughput sequencing data

    OpenAIRE

    Liu, Fang(Institute of High Energy Physics, Chinese Academy of Sciences, Beijing 100049, China)

    2016-01-01

    Jing Chang, Liya Huang, Qing Cao, Fang Liu Department of Gerontology, Xinhua Hospital Affiliated to Jiaotong University School of Medicine, Shanghai, People’s Republic of China Abstract: To identify potential key microRNAs (miRNAs) and their target genes for colorectal cancer (CRC). High-throughput sequencing data of miRNA expression and gene expression (ID: GSE46622) were downloaded from Gene Expression Omnibus, including matched colon tumor, normal colon epithelium, and liver me...

  7. MicroRNAs Associated with the Efficacy of Photodynamic Therapy in Biliary Tract Cancer Cell Lines

    Directory of Open Access Journals (Sweden)

    Andrej Wagner

    2014-11-01

    Full Text Available Photodynamic therapy (PDT is a palliative treatment option for unresectable hilar biliary tract cancer (BTC showing a considerable benefit for survival and quality of life with few side effects. Currently, factors determining the cellular response of BTC cells towards PDT are unknown. Due to their multifaceted nature, microRNAs (miRs are a promising analyte to investigate the cellular mechanisms following PDT. For two photosensitizers, Photofrin® and Foscan®, the phototoxicity was investigated in eight BTC cell lines. Each cell line (untreated was profiled for expression of n = 754 miRs using TaqMan® Array Human MicroRNA Cards. Statistical analysis and bioinformatic tools were used to identify miRs associated with PDT efficiency and their putative targets, respectively. Twenty miRs correlated significantly with either high or low PDT efficiency. PDT was particularly effective in cells with high levels of clustered miRs 25-93*-106b and (in case of miR-106b a phenotype characterized by high expression of the mesenchymal marker vimentin and high proliferation (cyclinD1 and Ki67 expression. Insensitivity towards PDT was associated with high miR-200 family expression and (for miR-cluster 200a/b-429 expression of differentiation markers Ck19 and Ck8/18. Predicted and validated downstream targets indicate plausible involvement of miRs 20a*, 25, 93*, 130a, 141, 200a, 200c and 203 in response mechanisms to PDT, suggesting that targeting these miRs could improve susceptibility to PDT in insensitive cell lines. Taken together, the miRNome pattern may provide a novel tool for predicting the efficiency of PDT and—following appropriate functional verification—may subsequently allow for optimization of the PDT protocol.

  8. MicroRNA-455 regulates brown adipogenesis via a novel HIF1an-AMPK-PGC1α signaling network

    DEFF Research Database (Denmark)

    Zhang, Hongbin; Guan, Meiping; Townsend, Kristy L;

    2015-01-01

    Brown adipose tissue (BAT) dissipates chemical energy as heat and can counteract obesity. MicroRNAs are emerging as key regulators in development and disease. Combining microRNA and mRNA microarray profiling followed by bioinformatic analyses, we identified miR-455 as a new regulator of brown...... adipogenesis. miR-455 exhibits a BAT-specific expression pattern and is induced by cold and the browning inducer BMP7. In vitro gain- and loss-of-function studies show that miR-455 regulates brown adipocyte differentiation and thermogenesis. Adipose-specific miR-455 transgenic mice display marked browning of...... data reveal a novel microRNA-regulated signaling network that controls brown adipogenesis and may be a potential therapeutic target for human metabolic disorders....

  9. MicroRNA-193b modulates proliferation, migration, and invasion of non-small cell lung cancer cells

    Institute of Scientific and Technical Information of China (English)

    Huajun Hu; Shangao Li; Jun Liu; Bin Ni

    2012-01-01

    MicroRNAs have been reported to be closely related to the development of human lung cancers.However,the functions of microRNAs in non-small cell lung cancer (NSCLC) remain largely undefined.Here,we investigated the role of microRNA-193b (miR-193b) in NSCLC.Our data showed that miR-193b was markedly down-regulated in NSCLC cancer tissues compared with adjacent normal tissues.The NSCLC cell line (A549) transfected with the miR-193b exhibited significantly decreased proliferation,migration,and invasion capacities when compared with the control cells.In contrast,inhibition of miR-193bincreased the proliferation,migration,and invasion of A549 cells.Moreover,miR-193b repressed the expressions of cyclin D1 and urokinase-type plasminogen activator in A549 cells.These data suggest that miR-193b is a tumor suppressor in NSCLC.

  10. Prognostic Value of MicroRNA-182 in Cancers: A Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Fei Wang

    2015-01-01

    Full Text Available Objective. MicroRNA-182 (miR-182 exhibits altered expression in various cancers. The aim of this study was to investigate the predictive value of miR-182 expression for cancer patient survival. Methods. Eligible studies were identified through multiple search strategies, and the hazard ratios (HRs for patient outcomes were extracted and estimated. A meta-analysis was performed to evaluate the prognostic value of miR-182. Results. In total, 14 studies were included. A high miR-182 expression level predicted a worse outcome with a pooled HR of 2.18 (95% CI: 1.53–3.11 in ten studies related to overall survival (OS, especially in Chinese populations. The results of seven studies evaluating disease-free survival/relapse-free survival/recurrence-free interval/disease-specific survival (DFS/RFS/RFI/DSS produced a pooled HR of 1.77 (95% CI: 0.91–3.43, which was not statistically significant; however, the trend was positive. When disregarding the DSS from one study, the expression of miR-182 was significantly correlated with DFS/RFS/RFI (pooled HR = 2.52, 95% CI: 1.67–3.79. Conclusions. High miR-182 expression is associated with poor OS and DFS/RFS/RFI in some types of cancers, and miR-182 may be a useful prognostic biomarker for predicting cancer prognosis. However, given the current insufficient relevant data, further clinical studies are needed.

  11. MicroRNAs as new Characters in the Plot between Epigenetics and Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Alessio ePaone

    2011-09-01

    Full Text Available Prostate cancer (PCA still represents a leading cause of death. An increasing number of studies have documented that microRNAs (miRNAs, a subgroup of non-coding RNAs with gene regulatory functions, are differentially expressed in PCA respect to the normal tissue counterpart, suggesting their involvement in prostate carcinogenesis and dissemination. Interestingly, it has been shown that miRNAs undergo the same regulatory mechanisms than any other protein coding gene, including epigenetic regulation. In turn, miRNAs can also affect the expression of oncogenes and tumor suppressor genes by targeting effectors of the epigenetic machinery, therefore indirectly affecting the epigenetic controls on these genes. Among the genes that undergo this complex regulation, there is the androgen receptor (AR, a key therapeutic target for PCA. This review will focus on the role of epigenetically regulated and epigenetically regulating miRNAs in prostate cancer and on the fine regulation of AR expression, as mediated by this miRNA-epigenetics interaction.

  12. Cancer and neurodegenerative disorders: pathogenic convergence through microRNA regulation

    Institute of Scientific and Technical Information of China (English)

    Liqin Du; Alexander Pertsemlidis

    2011-01-01

    Although cancer and neurodegenerative disease are two distinct pathological disorders, emerging evidence indicates that these two types of disease share common mechanisms of genetic and molecular abnormalities. Recent studies show that individual microRNAs (miRNAs) could be involved in the pathology of both diseases, indicating that the mechanisms of these two seemingly dichotomous diseases converge in the dysregulation of gene expression at the post-transcriptional level. Given the increasing evidence showing that miRNA-based therapeutic strategies that modulate the activity of one or more miRNAs are potentially effective for a wide range of pathological conditions, the involvement of miRNAs in the common pathways of leading both diseases suggests a bright future for developing common therapeutic approaches for both diseases. Moreover, the miRNAs that are dysregulated in both diseases may hold promise as uniquely informative diagnostic markers. Here, we review recent studies on the miRNAs that have been implicated in both cancer and neurodegenerative diseases.

  13. MicroRNA-21 directly targets MARCKS and promotes apoptosis resistance and invasion in prostate cancer cells

    International Nuclear Information System (INIS)

    Prostate cancer is one of the most common malignant cancers in men. Recent studies have shown that microRNA-21 (miR-21) is overexpressed in various types of cancers including prostate cancer. Studies on glioma, colon cancer cells, hepatocellular cancer cells and breast cancer cells have indicated that miR-21 is involved in tumor growth, invasion and metastasis. However, the roles of miR-21 in prostate cancer are poorly understood. In this study, the effects of miR-21 on prostate cancer cell proliferation, apoptosis, and invasion were examined. In addition, the targets of miR-21 were identified by a reported RISC-coimmunoprecipitation-based biochemical method. Inactivation of miR-21 by antisense oligonucleotides in androgen-independent prostate cancer cell lines DU145 and PC-3 resulted in sensitivity to apoptosis and inhibition of cell motility and invasion, whereas cell proliferation were not affected. We identified myristoylated alanine-rich protein kinase c substrate (MARCKS), which plays key roles in cell motility, as a new target in prostate cancer cells. Our data suggested that miR-21 could promote apoptosis resistance, motility, and invasion in prostate cancer cells and these effects of miR-21 may be partly due to its regulation of PDCD4, TPM1, and MARCKS. Gene therapy using miR-21 inhibition strategy may therefore be useful as a prostate cancer therapy.

  14. Exosome-shuttling microRNA-21 promotes cell migration and invasion-targeting PDCD4 in esophageal cancer.

    Science.gov (United States)

    Liao, Juan; Liu, Ran; Shi, Ya-Juan; Yin, Li-Hong; Pu, Yue-Pu

    2016-06-01

    Recent evidence indicates that exosomes can mediate certain microRNAs (miRNAs) involved in a series of biological functions in tumor occurrence and development. Our previous studies showed that microRNA-21 (miR-21) was abundant in both esophageal cancer cells and their corresponding exosomes. The present study explored the function of exosome-shuttling miR-21 involved in esophageal cancer progression. We found that exosomes could be internalized from the extracellular space to the cytoplasm. The exosome-derived Cy3-labeled miR-21 mimics could be transported into recipient cells in a neutral sphingomyelinase 2 (nSMase2)-dependent manner. miR-21 overexpression from donor cells significantly promoted the migration and invasion of recipient cells by targeting programmed cell death 4 (PDCD4) and activating its downstream c-Jun N-terminal kinase (JNK) signaling pathway after co-cultivation. Our population plasma sample analysis indicated that miR-21 was upregulated significantly in plasma from esophageal cancer patients and showed a significant risk association for esophageal cancer. Our data demonstrated that a close correlation existed between exosome-shuttling miR-21 and esophageal cancer recurrence and distant metastasis. Thus, exosome-shuttling miR-21 may become a potential biomarker for prognosis among esophageal cancer patients. PMID:27035745

  15. MicroRNAs and lung cancer: Biology and applications in diagnosis and prognosis

    OpenAIRE

    Mallick Reema; Patnaik Santosh; Yendamuri Sai

    2010-01-01

    MicroRNAs are tiny non-coding RNA molecules which play important roles in the epigenetic control of cellular processes by preventing the translation of proteins from messenger RNAs (mRNAs). A single microRNA can target different mRNAs, and an mRNA can be targeted by multiple microRNAs. Such complex interplays underlie many molecular pathways in cells, and specific roles for many microRNAs in physiological as well as pathological phenomena have been identified. Changes in expression of microRN...

  16. Expression of 6 MicroRNAs in Prostate Cancer and Its Significance

    Institute of Scientific and Technical Information of China (English)

    Ming Li; Liyu Cao; Hongfu Zhang; Yu Yin; Xiaochun Xu

    2009-01-01

    OBJECTIVE Numerous microRNAs (miRNAs) are deregulated in human cancers. The experimental evidence supports that miRNAs plays a role in the initiation and progression of human malignancies.The present study was undertaken to evaluate the differential expression of 6 miRNAs as biomarker for early detection of prostate cancer, and then to determine whether the expression profiling of these miRNAs could predict the prognosis of prostate cancer.METHODS The expression profilings of these 6 miRNAs were investigated using the method of locked nucleic acid (LNA)-modified oligonucleotide in situ hybridization (ISH). And the technology of tissue microarray (TMA) was employed using the formalin-fixed, paraffin-embedd (FFPE) specimens taken from 52 patients with prostate carcinoma (PCa) and 38 patients with benign prostatic hyperplasia (BPH).RESULTS The rates of positive expression for 6 miRNAs (miR-15b, miR-16, let-7g, miR- 96,miR-182 and miR-183) were 26.92%,15.38%o, 15.38%, 67.31%, 61.54% and 71.15% in the specimens of prostate cancer, and 57.89%, 76.32%, 68.42%, 44.74%, 31.58%,47.37% in the tissues of benign prostatic hyperplasia, respectively.The expressions of all 6 miRNAs between the prostate cancer and benign prostatic hyperplasia tissues were significantly different (P 0.05). We also found that the expression of miR-15b, miR-96 and miR-182 correlated with clinical stages of tumor (P 0.05). In addition, the expression of miR-15b was negatively related to that of miR-96,miR-182 and miR-183, respectively (P 0.00). The expression of miR-16 was positively related to that of miR-let-7g (P 0.00).CONCLUSION The results suggest that miRNA expression profiling could have relevance to the biological and clinical behavior of prostate cancer, and they might be important biomarkers for early detection and prognostic assessment of prostate cancer.

  17. Syndecan-1 responsive microRNA-126 and 149 regulate cell proliferation in prostate cancer

    Energy Technology Data Exchange (ETDEWEB)

    Fujii, Tomomi; Shimada, Keiji [Department of Pathology, Nara Medical University School of Medicine, Nara (Japan); Tatsumi, Yoshihiro [Department of Pathology, Nara Medical University School of Medicine, Nara (Japan); Department of Urology, Nara Medical University School of Medicine, Nara (Japan); Fujimoto, Kiyohide [Department of Urology, Nara Medical University School of Medicine, Nara (Japan); Konishi, Noboru, E-mail: nkonishi@naramed-u.ac.jp [Department of Pathology, Nara Medical University School of Medicine, Nara (Japan)

    2015-01-02

    Highlights: • Syndecan-1 is highly expressed in androgen independent prostate cancer cells, PC3. • Syndecan-1 regulates the expression of miR-126 and -149 in prostate cancer cells. • MiR-126 and 149 control cell growth via p21 induction and senescence mechanism. • MiR-126 and 149 promote cell proliferation by suppressing SOX2, NANOG, and Oct4. - Abstract: MicroRNAs (miRNAs) are short (19–24 nt), low molecular weight RNAs that play important roles in the regulation of target genes associated with cell proliferation, differentiation, and development, by binding to the 3′-untranslated region of the target mRNAs. In this study, we examined the expression of miRNA-126 (miR-126) and miR-149 in prostate cancer, and investigated the molecular mechanisms by which they affect syndecan-1 in prostate cancer. Functional analysis of miR-126 and miR-149 was conducted in the prostate cancer cell lines, PC3, Du145, and LNCaP. The expression levels of SOX2, NANOG, Oct4, miR-126 and miR-149 were evaluated by quantitative RT-PCR. After silencing syndecan-1, miR-126, and/or miR-149 in the PC3 cells, cell proliferation, senescence, and p21 induction were assessed using the MTS assay, senescence-associated β-galactosidase (SA-β-Gal) assay, and immunocytochemistry, respectively. Compared to the Du145 and LNCaP cells, PC3 cells exhibited higher expression of syndecan-1. When syndecan-1 was silenced, the PC3 cells showed reduced expression of miR-126 and miR-149 most effectively. Suppression of miR-126 and/or miR-149 significantly inhibited cell growth via p21 induction and subsequently, induced senescence. The mRNA expression levels of SOX2, NANOG, and Oct4 were significantly increased in response to the silencing of miR-126 and/or miR-149. Our results suggest that miR-126 and miR-149 are associated with the expression of syndecan-1 in prostate cancer cells. These miRNAs promote cell proliferation by suppressing SOX2, NANOG, and Oct4. The regulation of these factors by mi

  18. Syndecan-1 responsive microRNA-126 and 149 regulate cell proliferation in prostate cancer

    International Nuclear Information System (INIS)

    Highlights: • Syndecan-1 is highly expressed in androgen independent prostate cancer cells, PC3. • Syndecan-1 regulates the expression of miR-126 and -149 in prostate cancer cells. • MiR-126 and 149 control cell growth via p21 induction and senescence mechanism. • MiR-126 and 149 promote cell proliferation by suppressing SOX2, NANOG, and Oct4. - Abstract: MicroRNAs (miRNAs) are short (19–24 nt), low molecular weight RNAs that play important roles in the regulation of target genes associated with cell proliferation, differentiation, and development, by binding to the 3′-untranslated region of the target mRNAs. In this study, we examined the expression of miRNA-126 (miR-126) and miR-149 in prostate cancer, and investigated the molecular mechanisms by which they affect syndecan-1 in prostate cancer. Functional analysis of miR-126 and miR-149 was conducted in the prostate cancer cell lines, PC3, Du145, and LNCaP. The expression levels of SOX2, NANOG, Oct4, miR-126 and miR-149 were evaluated by quantitative RT-PCR. After silencing syndecan-1, miR-126, and/or miR-149 in the PC3 cells, cell proliferation, senescence, and p21 induction were assessed using the MTS assay, senescence-associated β-galactosidase (SA-β-Gal) assay, and immunocytochemistry, respectively. Compared to the Du145 and LNCaP cells, PC3 cells exhibited higher expression of syndecan-1. When syndecan-1 was silenced, the PC3 cells showed reduced expression of miR-126 and miR-149 most effectively. Suppression of miR-126 and/or miR-149 significantly inhibited cell growth via p21 induction and subsequently, induced senescence. The mRNA expression levels of SOX2, NANOG, and Oct4 were significantly increased in response to the silencing of miR-126 and/or miR-149. Our results suggest that miR-126 and miR-149 are associated with the expression of syndecan-1 in prostate cancer cells. These miRNAs promote cell proliferation by suppressing SOX2, NANOG, and Oct4. The regulation of these factors by mi

  19. Reliable microRNA profiling in routinely processed formalin-fixed paraffin-embedded breast cancer specimens using fluorescence labelled bead technology

    OpenAIRE

    Kreipe Hans; Christgen Matthias; Hasemeier Britta; Lehmann Ulrich

    2008-01-01

    Abstract Background During the last years the analysis of microRNA expression patterns has led to completely new insights into cancer biology. Furthermore, these patterns are a very promising tool for the development of new diagnostic and prognostic markers. However, most human tumour samples for which long term clinical records are available exist only as formalin-fixed paraffin-embedded specimens. Therefore, the aim of this study was to examine the feasibility of microRNA profiling studies ...

  20. Urine microRNAs as biomarkers for bladder cancer: a diagnostic meta-analysis

    Directory of Open Access Journals (Sweden)

    Cheng Y

    2015-08-01

    Full Text Available Yidong Cheng,* Xiaheng Deng,* Xiao Yang,* Pengchao Li, Xiaolei Zhang, Peng Li, Jun Tao, Qiang Lu, Zengjun Wang Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, People’s Republic of China *These authors contributed equally to this work Background: The diagnostic value of microRNA (miRNA detection in patients with bladder cancer (BCa is controversial. We performed a diagnostic meta-analysis to evaluate current evidence on the use of miRNA assays to diagnose BCa. Methods: We systematically searched PubMed, Embase, and Web of Science for studies published before March 31, 2015. The pooled sensitivity, specificity, positive and negative likelihood ratios, diagnostic odds ratio, and area under the curve (AUC were calculated to evaluate the overall test performance. Subgroup analyses were used to explore the between-study heterogeneity. Deeks’ funnel plot asymmetry test was used to test publication bias. We applied the software of RevMan 5.2 and Stata 11.0 to the meta-analysis. Results: A total of 23 studies from nine articles were included in the meta-analysis, with a total of 719 patients and 494 controls. The pooled sensitivity and specificity were 0.75 (95% confidence interval [CI], 0.68–0.80 and 0.75 (95% CI, 0.70–0.80, respectively. The pooled positive likelihood ratio was 3.03 (95% CI, 2.50–3.67; negative likelihood ratio was 0.33 (95% CI, 0.27–0.42; and diagnostic odds ratio was 9.07 (95% CI, 6.35–12.95. The pooled AUC was 0.81 (95% CI, 0.78–0.85. Subgroup analyses indicated that the multiple miRNAs assays and urine supernatant assays showed high accuracies in diagnosing BCa. Conclusion: The miRNA assays may serve as potential noninvasive diagnostic tool for the detection of BCa. However, the clinical application of miRNA assays for BCa diagnosis still needs further validation by large prospective studies. Keywords: microRNAs, bladder cancer, diagnostic accuracy, meta-analysis

  1. Subtype-specific micro-RNA expression signatures in breast cancer progression.

    Science.gov (United States)

    Haakensen, Vilde D; Nygaard, Vegard; Greger, Liliana; Aure, Miriam R; Fromm, Bastian; Bukholm, Ida R K; Lüders, Torben; Chin, Suet-Feung; Git, Anna; Caldas, Carlos; Kristensen, Vessela N; Brazma, Alvis; Børresen-Dale, Anne-Lise; Hovig, Eivind; Helland, Åslaug

    2016-09-01

    Robust markers of invasiveness may help reduce the overtreatment of in situ carcinomas. Breast cancer is a heterogeneous disease and biological mechanisms for carcinogenesis vary between subtypes. Stratification by subtype is therefore necessary to identify relevant and robust signatures of invasive disease. We have identified microRNA (miRNA) alterations during breast cancer progression in two separate datasets and used stratification and external validation to strengthen the findings. We analyzed two separate datasets (METABRIC and AHUS) consisting of a total of 186 normal breast tissue samples, 18 ductal carcinoma in situ (DCIS) and 1,338 invasive breast carcinomas. Validation in a separate dataset and stratification by molecular subtypes based on immunohistochemistry, PAM50 and integrated cluster classifications were performed. We propose subtype-specific miRNA signatures of invasive carcinoma and a validated signature of DCIS. miRNAs included in the invasive signatures include downregulation of miR-139-5p in aggressive subtypes and upregulation of miR-29c-5p expression in the luminal subtypes. No miRNAs were differentially expressed in the transition from DCIS to invasive carcinomas on the whole, indicating the need for subtype stratification. A total of 27 miRNAs were included in our proposed DCIS signature. Significant alterations of expression included upregulation of miR-21-5p and the miR-200 family and downregulation of let-7 family members in DCIS samples. The signatures proposed here can form the basis for studies exploring DCIS samples with increased invasive potential and serum biomarkers for in situ and invasive breast cancer. PMID:27082076

  2. Single-nucleotide polymorphisms of microRNA processing machinery genes and risk of colorectal cancer

    Directory of Open Access Journals (Sweden)

    Zhao Y

    2015-02-01

    Full Text Available Yufei Zhao, Yanming Du, Shengnan Zhao, Zhanjun GuoDepartment of Gastroenterology and Hepatology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, People’s Republic of ChinaObjective: MicroRNA (miRNA-related single-nucleotide polymorphisms (miR-SNPs in miRNA processing machinery genes can affect cancer risk, treatment efficacy, and patient prognosis. We genotyped 6 miR-SNPs of miRNA processing machinery genes including XPO5 (rs11077, RAN (rs14035, Dicer (rs3742330, TNRC6B (rs9623117, GEMIN3 (rs197412, and GEMIN4 (rs2740348 in a case-control study to evaluate their impact on colorectal cancer (CRC risk.Materials and methods: miR-SNPs were genotyped using the polymerase chain reaction–ligase detection reaction. The Χ2 test was used to analyze dichotomous values, such as the presence or absence of any individual SNP in CRC patients and healthy controls.Results: Two of these SNPs were identified for their association with cancer risk in the Dicer and GEMIN3 genes. The AA allele of rs3742330 located in the Dicer gene exhibited a significantly increased risk of CRC (odds ratio, 2.11; 95% confidence interval: 1.33–3.34; P=0.001; the TT allele of rs197412 located in GEMIN3 also exhibited a significantly increased risk of CRC (odds ratio, 1.68; 95% confidence interval: 1.07–2.65; P=0.024.Conclusion: Our results suggest that the specific genetic variants in miRNA machinery genes may affect CRC susceptibility.Keywords: miR-SNP, CRC, GEMIN3, Dicer

  3. Global microRNA expression profiling of high-risk ER+ breast cancers from patients receiving adjuvant tamoxifen mono-therapy

    DEFF Research Database (Denmark)

    Lyng, Maria Bibi; Lænkholm, Anne-Vibeke; Søkilde, Rolf;

    2012-01-01

    Despite the benefits of estrogen receptor (ER)-targeted endocrine therapies in breast cancer, many tumors develop resistance. MicroRNAs (miRNAs) have been suggested as promising biomarkers and we here evaluated whether a miRNA profile could be identified, sub-grouping ER+ breast cancer patients t...... treated with adjuvant Tamoxifen with regards to probability of recurrence....

  4. The role of microRNA-1274a in the tumorigenesis of gastric cancer: Accelerating cancer cell proliferation and migration via directly targeting FOXO4

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Guo-Jun, E-mail: wwangguojun@163.com; Liu, Guang-Hui; Ye, Yan-Wei; Fu, Yang; Zhang, Xie-Fu

    2015-04-17

    MicroRNAs (miRNAs) are a series of 18–25 nucleotides length non-coding RNAs, which play critical roles in tumorigenesis. Previous study has shown that microRNA-1274a (miR-1274a) is upregulated in human gastric cancer. However, its role in gastric cancer progression remains poorly understood. Therefore, the current study was aimed to examine the effect of miR-1274a on gastric cancer cells. We found that miR-1274a was overexpressed in gastric cancer tissues or gastric cancer cells including HGC27, MGC803, AGS, and SGC-7901 by qRT-PCR analysis. Transfection of miR-1274a markedly promoted gastric cancer cells proliferation and migration as well as induced epithelial–mesenchymal transition (EMT) of cancer cells. Our further examination identified FOXO4 as a target of miR-1274a, which did not influence FOXO4 mRNA expression but significantly inhibited FOXO4 protein expression. Moreover, miR-1274a overexpression activated PI3K/Akt signaling and upregulated cyclin D1, MMP-2 and MMP-9 expressions. With tumor xenografts in mice models, we also showed that miR-1274a promoted tumorigenesis of gastric cancer in vivo. In all, our study demonstrated that miR-1274a prompted gastric cancer cells growth and migration through dampening FOXO4 expression thus provided a potential target for human gastric cancer therapy. - Highlights: • MiR-1274a expression was augmented in gastric cancer. • MiR-1274a promoted proliferation, migration and induced EMT in cancer cells. • MiR-1274a directly targeted FOXO4 expression. • MiR-1274a triggered PI3K/Akt signaling in cancer cells. • MiR-1274a significantly increased tumor xenografts growth.

  5. The role of microRNA-1274a in the tumorigenesis of gastric cancer: Accelerating cancer cell proliferation and migration via directly targeting FOXO4

    International Nuclear Information System (INIS)

    MicroRNAs (miRNAs) are a series of 18–25 nucleotides length non-coding RNAs, which play critical roles in tumorigenesis. Previous study has shown that microRNA-1274a (miR-1274a) is upregulated in human gastric cancer. However, its role in gastric cancer progression remains poorly understood. Therefore, the current study was aimed to examine the effect of miR-1274a on gastric cancer cells. We found that miR-1274a was overexpressed in gastric cancer tissues or gastric cancer cells including HGC27, MGC803, AGS, and SGC-7901 by qRT-PCR analysis. Transfection of miR-1274a markedly promoted gastric cancer cells proliferation and migration as well as induced epithelial–mesenchymal transition (EMT) of cancer cells. Our further examination identified FOXO4 as a target of miR-1274a, which did not influence FOXO4 mRNA expression but significantly inhibited FOXO4 protein expression. Moreover, miR-1274a overexpression activated PI3K/Akt signaling and upregulated cyclin D1, MMP-2 and MMP-9 expressions. With tumor xenografts in mice models, we also showed that miR-1274a promoted tumorigenesis of gastric cancer in vivo. In all, our study demonstrated that miR-1274a prompted gastric cancer cells growth and migration through dampening FOXO4 expression thus provided a potential target for human gastric cancer therapy. - Highlights: • MiR-1274a expression was augmented in gastric cancer. • MiR-1274a promoted proliferation, migration and induced EMT in cancer cells. • MiR-1274a directly targeted FOXO4 expression. • MiR-1274a triggered PI3K/Akt signaling in cancer cells. • MiR-1274a significantly increased tumor xenografts growth

  6. Differentially expressed microRNAs in postpartum breast cancer in Hispanic women.

    Directory of Open Access Journals (Sweden)

    José L Muñoz-Rodríguez

    Full Text Available The risk of breast cancer transiently increases immediately following pregnancy; peaking between 3-7 years. The biology that underlies this risk window and the effect on the natural history of the disease is unknown. MicroRNAs (miRNAs are small non-coding RNAs that have been shown to be dysregulated in breast cancer. We conducted miRNA profiling of 56 tumors from a case series of multiparous Hispanic women and assessed the pattern of expression by time since last full-term pregnancy. A data-driven splitting analysis on the pattern of 355 miRNAs separated the case series into two groups: a an early group representing women diagnosed with breast cancer ≤ 5.2 years postpartum (n = 12, and b a late group representing women diagnosed with breast cancer ≥ 5.3 years postpartum (n = 44. We identified 15 miRNAs with significant differential expression between the early and late postpartum groups; 60% of these miRNAs are encoded on the X chromosome. Ten miRNAs had a two-fold or higher difference in expression with miR-138, miR-660, miR-31, miR-135b, miR-17, miR-454, and miR-934 overexpressed in the early versus the late group; while miR-892a, miR-199a-5p, and miR-542-5p were underexpressed in the early versus the late postpartum group. The DNA methylation of three out of five tested miRNAs (miR-31, miR-135b, and miR-138 was lower in the early versus late postpartum group, and negatively correlated with miRNA expression. Here we show that miRNAs are differentially expressed and differentially methylated between tumors of the early versus late postpartum, suggesting that potential differences in epigenetic dysfunction may be operative in postpartum breast cancers.

  7. Differentially expressed microRNAs in postpartum breast cancer in Hispanic women.

    Science.gov (United States)

    Muñoz-Rodríguez, José L; Vrba, Lukas; Futscher, Bernard W; Hu, Chengcheng; Komenaka, Ian K; Meza-Montenegro, Maria Mercedes; Gutierrez-Millan, Luis Enrique; Daneri-Navarro, Adrian; Thompson, Patricia A; Martinez, Maria Elena

    2015-01-01

    The risk of breast cancer transiently increases immediately following pregnancy; peaking between 3-7 years. The biology that underlies this risk window and the effect on the natural history of the disease is unknown. MicroRNAs (miRNAs) are small non-coding RNAs that have been shown to be dysregulated in breast cancer. We conducted miRNA profiling of 56 tumors from a case series of multiparous Hispanic women and assessed the pattern of expression by time since last full-term pregnancy. A data-driven splitting analysis on the pattern of 355 miRNAs separated the case series into two groups: a) an early group representing women diagnosed with breast cancer ≤ 5.2 years postpartum (n = 12), and b) a late group representing women diagnosed with breast cancer ≥ 5.3 years postpartum (n = 44). We identified 15 miRNAs with significant differential expression between the early and late postpartum groups; 60% of these miRNAs are encoded on the X chromosome. Ten miRNAs had a two-fold or higher difference in expression with miR-138, miR-660, miR-31, miR-135b, miR-17, miR-454, and miR-934 overexpressed in the early versus the late group; while miR-892a, miR-199a-5p, and miR-542-5p were underexpressed in the early versus the late postpartum group. The DNA methylation of three out of five tested miRNAs (miR-31, miR-135b, and miR-138) was lower in the early versus late postpartum group, and negatively correlated with miRNA expression. Here we show that miRNAs are differentially expressed and differentially methylated between tumors of the early versus late postpartum, suggesting that potential differences in epigenetic dysfunction may be operative in postpartum breast cancers. PMID:25875827

  8. Network of microRNAs-mRNAs Interactions in Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Elnaz Naderi

    2014-01-01

    Full Text Available Background. MicroRNAs are small RNA molecules that regulate the expression of certain genes through interaction with mRNA targets and are mainly involved in human cancer. This study was conducted to make the network of miRNAs-mRNAs interactions in pancreatic cancer as the fourth leading cause of cancer death. Methods. 56 miRNAs that were exclusively expressed and 1176 genes that were downregulated or silenced in pancreas cancer were extracted from beforehand investigations. MiRNA–mRNA interactions data analysis and related networks were explored using MAGIA tool and Cytoscape 3 software. Functional annotations of candidate genes in pancreatic cancer were identified by DAVID annotation tool. Results. This network is made of 217 nodes for mRNA, 15 nodes for miRNA, and 241 edges that show 241 regulations between 15 miRNAs and 217 target genes. The miR-24 was the most significantly powerful miRNA that regulated series of important genes. ACVR2B, GFRA1, and MTHFR were significant target genes were that downregulated. Conclusion. Although the collected previous data seems to be a treasure trove, there was no study simultaneous to analysis of miRNAs and mRNAs interaction. Network of miRNA-mRNA interactions will help to corroborate experimental remarks and could be used to refine miRNA target predictions for developing new therapeutic approaches.

  9. Mutator activity induced by microRNA-155 (miR-155) links inflammation and cancer.

    Science.gov (United States)

    Tili, Esmerina; Michaille, Jean-Jacques; Wernicke, Dorothee; Alder, Hansjuerg; Costinean, Stefan; Volinia, Stefano; Croce, Carlo M

    2011-03-22

    Infection-driven inflammation has been implicated in the pathogenesis of ~15-20% of human tumors. Expression of microRNA-155 (miR-155) is elevated during innate immune response and autoimmune disorders as well as in various malignancies. However, the molecular mechanisms providing miR-155 with its oncogenic properties remain unclear. We examined the effects of miR-155 overexpression and proinflammatory environment on the frequency of spontaneous hypoxanthine phosphoribosyltransferase (HPRT) mutations that can be detected based on the resistance to 6-thioguanine. Both miR-155 overexpression and inflammatory environment increased the frequency of HPRT mutations and down-regulated WEE1 (WEE1 homolog-S. pombe), a kinase that blocks cell-cycle progression. The increased frequency of HPRT mutation was only modestly attributable to defects in mismatch repair machinery. This result suggests that miR-155 enhances the mutation rate by simultaneously targeting different genes that suppress mutations and decreasing the efficiency of DNA safeguard mechanisms by targeting of cell-cycle regulators such as WEE1. By simultaneously targeting tumor suppressor genes and inducing a mutator phenotype, miR-155 may allow the selection of gene alterations required for tumor development and progression. Hence, we anticipate that the development of drugs reducing endogenous miR-155 levels might be key in the treatment of inflammation-related cancers. PMID:21383199

  10. MicroRNAs in Cancer: A Historical Perspective on the Path from Discovery to Therapy

    Directory of Open Access Journals (Sweden)

    Esteban A. Orellana

    2015-07-01

    Full Text Available Recent progress in microRNA (miRNA therapeutics has been strongly dependent on multiple seminal discoveries in the area of miRNA biology during the past two decades. In this review, we focus on the historical discoveries that collectively led to transitioning miRNAs into the clinic. We highlight the pivotal studies that identified the first miRNAs in Caenorhabditis elegans to the more recent reports that have fueled the quest to understand the use of miRNAs as markers for cancer diagnosis and prognosis. In addition, we provide insights as to how unraveling basic miRNA biology has provided a solid foundation for advancing miRNAs, such as miR-34a, therapeutically. We conclude with a brief examination of the current challenges that still need to be addressed to accelerate the path of miRNAs to the clinic: including delivery vehicles, miRNA- and delivery-associated toxicity, dosage, and off target effects.

  11. miR-1 and miR-145 act as tumor suppressor microRNAs in gallbladder cancer.

    Science.gov (United States)

    Letelier, Pablo; García, Patricia; Leal, Pamela; Álvarez, Héctor; Ili, Carmen; López, Jaime; Castillo, Jonathan; Brebi, Priscilla; Roa, Juan Carlos

    2014-01-01

    The development of miRNA-based therapeutics represents a new strategy in cancer treatment. The objectives of this study were to evaluate the differential expression of microRNAs in gallbladder cancer (GBC) and to assess the functional role of miR-1 and miR-145 in GBC cell behavior. A profile of miRNA expression was determined using DharmaconTM microarray technology. Differential expression of five microRNAs was validated by TaqMan reverse transcription quantitative-PCR in a separate cohort of 8 tumors and 3 non-cancerous samples. Then, we explored the functional role of miR-1 and miR-145 in tumor cell behavior by ectopic in vitro expression in the GBC NOZ cell line. Several miRNAs were found to be aberrantly expressed in GBC; most of these showed a significantly decreased expression compared to non-neoplastic tissues (Q valueanalysis revealed that the most deregulated miRNAs (miR-1, miR-133, miR-143 and miR-145) collectively targeted a number of genes belonging to signaling pathways such as TGF-β, ErbB3, WNT and VEGF, and those regulating cell motility or adhesion. The ectopic expression of miR-1 and miR-145 in NOZ cells significantly inhibited cell viability and colony formation (P<0.01) and reduced gene expression of VEGF-A and AXL. This study represents the first investigation of the miRNA expression profile in gallbladder cancer, and our findings showed that several miRNAs are deregulated in this neoplasm. In vitro functional assays suggest that miR-1 and miR-145 act as tumor suppressor microRNAs in GBC. PMID:24966896

  12. Potential Diagnostic, Prognostic and Therapeutic Targets of MicroRNAs in Human Gastric Cancer

    Directory of Open Access Journals (Sweden)

    Ming-Ming Tsai

    2016-06-01

    Full Text Available Human gastric cancer (GC is characterized by a high incidence and mortality rate, largely because it is normally not identified until a relatively advanced stage owing to a lack of early diagnostic biomarkers. Gastroscopy with biopsy is the routine method for screening, and gastrectomy is the major therapeutic strategy for GC. However, in more than 30% of GC surgical patients, cancer has progressed too far for effective medical resection. Thus, useful biomarkers for early screening or detection of GC are essential for improving patients’ survival rate. MicroRNAs (miRNAs play an important role in tumorigenesis. They contribute to gastric carcinogenesis by altering the expression of oncogenes and tumor suppressors. Because of their stability in tissues, serum/plasma and other body fluids, miRNAs have been suggested as novel tumor biomarkers with suitable clinical potential. Recently, aberrantly expressed miRNAs have been identified and tested for clinical application in the management of GC. Aberrant miRNA expression profiles determined with miRNA microarrays, quantitative reverse transcription-polymerase chain reaction and next-generation sequencing approaches could be used to establish sample specificity and to identify tumor type. Here, we provide an up-to-date summary of tissue-based GC-associated miRNAs, describing their involvement and that of their downstream targets in tumorigenic and biological processes. We examine correlations among significant clinical parameters and prognostic indicators, and discuss recurrence monitoring and therapeutic options in GC. We also review plasma/serum-based, GC-associated, circulating miRNAs and their clinical applications, focusing especially on early diagnosis. By providing insights into the mechanisms of miRNA-related tumor progression, this review will hopefully aid in the identification of novel potential therapeutic targets.

  13. MicroRNA MIR21 and T Cells in Colorectal Cancer.

    Science.gov (United States)

    Mima, Kosuke; Nishihara, Reiko; Nowak, Jonathan A; Kim, Sun A; Song, Mingyang; Inamura, Kentaro; Sukawa, Yasutaka; Masuda, Atsuhiro; Yang, Juhong; Dou, Ruoxu; Nosho, Katsuhiko; Baba, Hideo; Giovannucci, Edward L; Bowden, Michaela; Loda, Massimo; Giannakis, Marios; Bass, Adam J; Dranoff, Glenn; Freeman, Gordon J; Chan, Andrew T; Fuchs, Charles S; Qian, Zhi Rong; Ogino, Shuji

    2016-01-01

    The complex interactions between colorectal neoplasia and immune cells in the tumor microenvironment remain to be elucidated. Experimental evidence suggests that microRNA MIR21 (miR-21) suppresses antitumor T-cell-mediated immunity. Thus, we hypothesized that tumor MIR21 expression might be inversely associated with T-cell density in colorectal carcinoma tissue. Using 538 rectal and colon cancer cases from the Nurses' Health Study and the Health Professionals Follow-up Study, we measured tumor MIR21 expression by a quantitative reverse-transcription PCR assay. Densities of CD3(+), CD8(+), CD45RO (PTPRC)(+), and FOXP3(+) cells in tumor tissue were determined by tissue microarray immunohistochemistry and computer-assisted image analysis. Ordinal logistic regression analysis was conducted to assess the association of MIR21 expression (ordinal quartiles as a predictor variable) with T-cell density (ordinal quartiles as an outcome variable), adjusting for tumor molecular features, including microsatellite instability; CpG island methylator phenotype; KRAS, BRAF, and PIK3CA mutations; and LINE-1 methylation. We adjusted the two-sided α level to 0.012 for multiple hypothesis testing. Tumor MIR21 expression was inversely associated with densities of CD3(+) and CD45RO(+) cells (Ptrend confidence interval (CI), 0.28 to 0.68] or 0.41 (95% CI, 0.26-0.64), respectively. Our data support a possible role of tumor epigenetic deregulation by noncoding RNA in suppressing the antitumor T-cell-mediated adaptive immune response and suggest MIR21 as a potential target for immunotherapy and prevention in colorectal cancer. PMID:26419959

  14. Interaction between Wnt/β-catenin pathway and microRNAs regulates epithelial-mesenchymal transition in gastric cancer (Review).

    Science.gov (United States)

    Wu, Cunen; Zhuang, Yuwen; Jiang, Shan; Liu, Shenlin; Zhou, Jinyong; Wu, Jian; Teng, Yuhao; Xia, Baomei; Wang, Ruiping; Zou, Xi

    2016-06-01

    Gastric cancer (GC) is the third primary cause of cancer-related mortality and one of the most common type of malignant diseases worldwide. Despite remarkable progress in multimodality therapy, advanced GC with high aggressiveness always ends in treatment failure. Epithelial-mesenchymal transition (EMT) has been widely recognized to be a key process associating with GC evolution, during which cancer cells go through phenotypic variations and acquire the capability of migration and invasion. Wnt/β-catenin pathway has established itself as an EMT regulative signaling due to its maintenance of epithelial integrity as well as tight adherens junctions while mutations of its components will lead to GC initiation and diffusion. The E-cadherin/β-catenin complex plays an important role in stabilizing β-catenin at cell membrane while disruption of this compound gives rise to nuclear translocation of β-catenin, which accounts for upregulation of EMT biomarkers and unfavorable prognosis. Additionally, several microRNAs positively or negatively modify EMT by reciprocally acting with certain target genes of Wnt/β-catenin pathway in GC. Thus, this review centers on the strong associations between Wnt/β-catenin pathway and microRNAs during alteration of EMT in GC, which may induce advantageous therapeutic strategies for human gastric cancer. PMID:27082441

  15. Interactions between E-Cadherin and MicroRNA Deregulation in Head and Neck Cancers: The Potential Interplay

    Directory of Open Access Journals (Sweden)

    Thian-Sze Wong

    2014-01-01

    Full Text Available E-cadherin expression in the head and neck epithelium is essential for the morphogenesis and homeostasis of epithelial tissues. The cadherin-mediated cell-cell contacts are required for the anchorage-dependent growth of epithelial cells. Further, survival and proliferation require physical tethering created by proper cell-cell adhesion. Otherwise, the squamous epithelial cells will undergo programmed cell death. Head and neck cancers can escape from anoikis and enter into the epithelial-mesenchymal transition stages via the modulation of E-cadherin expression with epigenetic mechanisms. At epigenetic level, gene expression control is not dependent on the DNA sequence. In the context of E-cadherin regulation in head and neck cancers, 2 major mechanisms including de novo promoter hypermethylation and microRNA dysregulation are most extensively studied. Both of them control E-cadherin expression at transcription level and subsequently hinder the overall E-cadherin protein level in the head and neck cancer cells. Increasing evidence suggested that microRNA mediated E-cadherin expression in the head and neck cancers by directly/indirectly targeting the transcription suppressors of E-cadherin, ZEB1 and ZEB2.

  16. Detection of gene communities in multi-networks reveals cancer drivers

    Science.gov (United States)

    Cantini, Laura; Medico, Enzo; Fortunato, Santo; Caselle, Michele

    2015-12-01

    We propose a new multi-network-based strategy to integrate different layers of genomic information and use them in a coordinate way to identify driving cancer genes. The multi-networks that we consider combine transcription factor co-targeting, microRNA co-targeting, protein-protein interaction and gene co-expression networks. The rationale behind this choice is that gene co-expression and protein-protein interactions require a tight coregulation of the partners and that such a fine tuned regulation can be obtained only combining both the transcriptional and post-transcriptional layers of regulation. To extract the relevant biological information from the multi-network we studied its partition into communities. To this end we applied a consensus clustering algorithm based on state of art community detection methods. Even if our procedure is valid in principle for any pathology in this work we concentrate on gastric, lung, pancreas and colorectal cancer and identified from the enrichment analysis of the multi-network communities a set of candidate driver cancer genes. Some of them were already known oncogenes while a few are new. The combination of the different layers of information allowed us to extract from the multi-network indications on the regulatory pattern and functional role of both the already known and the new candidate driver genes.

  17. Downregulation of microRNA-362-3p and microRNA-329 promotes tumor progression in human breast cancer.

    Science.gov (United States)

    Kang, H; Kim, C; Lee, H; Rho, J G; Seo, J-W; Nam, J-W; Song, W K; Nam, S W; Kim, W; Lee, E K

    2016-03-01

    p130Cas regulates cancer progression by driving tyrosine receptor kinase signaling. Tight regulation of p130Cas expression is necessary for survival, apoptosis, and maintenance of cell motility in various cell types. Several studies revealed that transcriptional and post-translational control of p130Cas are important for maintenance of its expression and activity. To explore novel regulatory mechanisms of p130Cas expression, we studied the effect of microRNAs (miRs) on p130Cas expression in human breast cancer MCF7 cells. Here, we provide experimental evidence that miR-362-3p and miR-329 perform a tumor-suppressive function and their expression is downregulated in human breast cancer. miR-362-3p and miR-329 inhibited cellular proliferation, migration, and invasion, thereby suppressing tumor growth, by downregulating p130Cas. Ectopic expression of p130Cas attenuated the inhibitory effects of the two miRs on tumor progression. Relative expression levels of miR-362-3p/329 and p130Cas between normal and breast cancer correlated inversely; miR-362-3p/329 expression was decreased, whereas that of p130Cas increased in breast cancers. Furthermore, we showed that downregulation of miR-362-3p and miR-329 was caused by differential DNA methylation of miR genes. Enhanced DNA methylation (according to methylation-specific PCR) was responsible for downregulation of miR-362-3p and miR-329 in breast cancer. Taken together, these findings point to a novel role for miR-362-3p and miR-329 as tumor suppressors; the miR-362-3p/miR-329-p130Cas axis seemingly has a crucial role in breast cancer progression. Thus, modulation of miR-362-3p/miR-329 may be a novel therapeutic strategy against breast cancer. PMID:26337669

  18. NAViGaTing the micronome--using multiple microRNA prediction databases to identify signalling pathway-associated microRNAs.

    Directory of Open Access Journals (Sweden)

    Elize A Shirdel

    Full Text Available BACKGROUND: MicroRNAs are a class of small RNAs known to regulate gene expression at the transcript level, the protein level, or both. Since microRNA binding is sequence-based but possibly structure-specific, work in this area has resulted in multiple databases storing predicted microRNA:target relationships computed using diverse algorithms. We integrate prediction databases, compare predictions to in vitro data, and use cross-database predictions to model the microRNA:transcript interactome--referred to as the micronome--to study microRNA involvement in well-known signalling pathways as well as associations with disease. We make this data freely available with a flexible user interface as our microRNA Data Integration Portal--mirDIP (http://ophid.utoronto.ca/mirDIP. RESULTS: mirDIP integrates prediction databases to elucidate accurate microRNA:target relationships. Using NAViGaTOR to produce interaction networks implicating microRNAs in literature-based, KEGG-based and Reactome-based pathways, we find these signalling pathway networks have significantly more microRNA involvement compared to chance (p<0.05, suggesting microRNAs co-target many genes in a given pathway. Further examination of the micronome shows two distinct classes of microRNAs; universe microRNAs, which are involved in many signalling pathways; and intra-pathway microRNAs, which target multiple genes within one signalling pathway. We find universe microRNAs to have more targets (p<0.0001, to be more studied (p<0.0002, and to have higher degree in the KEGG cancer pathway (p<0.0001, compared to intra-pathway microRNAs. CONCLUSIONS: Our pathway-based analysis of mirDIP data suggests microRNAs are involved in intra-pathway signalling. We identify two distinct classes of microRNAs, suggesting a hierarchical organization of microRNAs co-targeting genes both within and between pathways, and implying differential involvement of universe and intra-pathway microRNAs at the disease level.

  19. Microrheology of keratin networks in cancer cells

    International Nuclear Information System (INIS)

    Microrheology is a valuable tool to determine viscoelastic properties of polymer networks. For this purpose measurements with embedded tracer beads inside the extracted network of pancreatic cancer cells were performed. Observing the beads motion with a CCD-high-speed-camera leads to the dynamic shear modulus. The complex shear modulus is divided into real and imaginary parts which give insight into the mechanical properties of the cell. The dependency on the distance of the embedded beads to the rim of the nucleus shows a tendency for a deceasing storage modulus. We draw conclusions on the network topology of the keratin network types based on the mechanical behavior. (paper)

  20. Microrheology of keratin networks in cancer cells.

    Science.gov (United States)

    Paust, T; Paschke, S; Beil, M; Marti, O

    2013-12-01

    Microrheology is a valuable tool to determine viscoelastic properties of polymer networks. For this purpose measurements with embedded tracer beads inside the extracted network of pancreatic cancer cells were performed. Observing the beads motion with a CCD-high-speed-camera leads to the dynamic shear modulus. The complex shear modulus is divided into real and imaginary parts which give insight into the mechanical properties of the cell. The dependency on the distance of the embedded beads to the rim of the nucleus shows a tendency for a decreasing storage modulus. We draw conclusions on the network topology of the keratin network types based on the mechanical behavior. PMID:24305115

  1. Graph Curvature for Differentiating Cancer Networks

    Science.gov (United States)

    Sandhu, Romeil; Georgiou, Tryphon; Reznik, Ed; Zhu, Liangjia; Kolesov, Ivan; Senbabaoglu, Yasin; Tannenbaum, Allen

    2015-07-01

    Cellular interactions can be modeled as complex dynamical systems represented by weighted graphs. The functionality of such networks, including measures of robustness, reliability, performance, and efficiency, are intrinsically tied to the topology and geometry of the underlying graph. Utilizing recently proposed geometric notions of curvature on weighted graphs, we investigate the features of gene co-expression networks derived from large-scale genomic studies of cancer. We find that the curvature of these networks reliably distinguishes between cancer and normal samples, with cancer networks exhibiting higher curvature than their normal counterparts. We establish a quantitative relationship between our findings and prior investigations of network entropy. Furthermore, we demonstrate how our approach yields additional, non-trivial pair-wise (i.e. gene-gene) interactions which may be disrupted in cancer samples. The mathematical formulation of our approach yields an exact solution to calculating pair-wise changes in curvature which was computationally infeasible using prior methods. As such, our findings lay the foundation for an analytical approach to studying complex biological networks.

  2. Graph Curvature for Differentiating Cancer Networks

    Science.gov (United States)

    Sandhu, Romeil; Georgiou, Tryphon; Reznik, Ed; Zhu, Liangjia; Kolesov, Ivan; Senbabaoglu, Yasin; Tannenbaum, Allen

    2015-01-01

    Cellular interactions can be modeled as complex dynamical systems represented by weighted graphs. The functionality of such networks, including measures of robustness, reliability, performance, and efficiency, are intrinsically tied to the topology and geometry of the underlying graph. Utilizing recently proposed geometric notions of curvature on weighted graphs, we investigate the features of gene co-expression networks derived from large-scale genomic studies of cancer. We find that the curvature of these networks reliably distinguishes between cancer and normal samples, with cancer networks exhibiting higher curvature than their normal counterparts. We establish a quantitative relationship between our findings and prior investigations of network entropy. Furthermore, we demonstrate how our approach yields additional, non-trivial pair-wise (i.e. gene-gene) interactions which may be disrupted in cancer samples. The mathematical formulation of our approach yields an exact solution to calculating pair-wise changes in curvature which was computationally infeasible using prior methods. As such, our findings lay the foundation for an analytical approach to studying complex biological networks. PMID:26169480

  3. 胃癌相关microRNA的研究%The research of microRNA in gastric cancer

    Institute of Scientific and Technical Information of China (English)

    李尔萃; 王学红; 范钟麟

    2012-01-01

    As a participant in a series of life processes by its regulation and control over the genetic expression, the microRNA has been proved to be effective, sensitive and excellent in marking tumour, suggesting diagnostic marker and thraputic target. At present, the experimental progress has been achieved in the research of microRNA now regarded as a marker of the biological therapy. In this article, a summary is made of the microRNA study concerning gastric cancer.%microRNA通过对基因表达的调控参与生命过程中一系列重要进程.它对肿瘤的标记高效、敏感而特异,提示其可能成为众多疾病有价值的诊断标志物和治疗靶点.目前,microRNA作为生物学治疗靶标已经取得实验性进展.本文就胃癌相关microRNA的研究进展做一综述.

  4. MicroRNA-106b targets FUT6 to promote cell migration, invasion, and proliferation in human breast cancer.

    Science.gov (United States)

    Li, Nana; Liu, Yuejian; Miao, Yuan; Zhao, Lifen; Zhou, Huimin; Jia, Li

    2016-09-01

    It is demonstrated that the maladjustment of microRNA (miRNA) plays significant roles in the occurrence and development of tumors. MicroRNA-106b-5p (miR-106b), a carcinogenic miRNA, is identified as a dysregulated miRNA in human breast cancer. In this article, the expression levels of miR-106b were discovered to be particularly higher in breast cancer tissues than that in the corresponding adjacent tissues. Accordingly, miR-106b was higher expressed in the breast cancer cell lines compared with that in the normal breast cell lines. Moreover, according to the data previously reported, increased expression of miR-106b was significantly associated with advanced clinical stages and poor prognosis in breast cancer. Fucosyltransferase 6 (FUT6), a member of the fucosyltransferase (FUT) family, was found to have a reduced expression in tissues or cells with higher level of miR-106b in breast cancer. Additionally, down-regulation of miR-106b increased the expression of FUT6 and resulted in an obvious decrease of cell migration, invasion, and proliferation in MDA-MB-231 cells. Furthermore, over-expressed FUT6 reversed the impacts of up-regulated miR-106b on cell migration, invasion, and proliferation in MCF-7 cells, indicating that FUT6 might be directly targeted by miR-106b and serve as therapeutic targets for breast cancer. In brief, our results strongly showed that the low expression of FUT6 regulated by miR-106b contributed to cell migration, invasion, and proliferation in human breast cancer. © 2016 IUBMB Life, 68(9):764-775, 2016. PMID:27519168

  5. Inferring coregulation of transcription factors and microRNAs in breast cancer.

    Science.gov (United States)

    Wu, Jia-Hong; Sun, Yun-Ju; Hsieh, Ping-Heng; Shieh, Grace S

    2013-04-10

    Both transcription factors (TFs) and microRNAs (miRNAs) regulate gene expression. TFs activate or suppress the initiation of the transcription process and miRNAs regulate mRNAs post-transcriptionally, thus forming a temporally ordered regulatory event. Ectopic expression of key transcriptional regulators and/or miRNAs has been shown to be involved in various tumors. Therefore, uncovering the coregulation of TFs and miRNAs in human cancers may lead to the discovery of novel therapeutics. We introduced a two-stage learning fuzzy method to model TF-miRNA coregulation using both genomic data and verified regulatory relationships. In Stage 1, a learning (adaptive) fuzzy inference system (ANFIS) combines two sequence alignment features of TF and target by learning from verified TF-target pairs into a sequence matching score. Next, a non-learning FIS incorporates a sequence alignment score and a correlation score from paired TF-target gene expression to output a Stage 1 fuzzy score to infer whether a TF-target regulation exists. For significant TF-target pairs, in Stage 2, similar to Stage 1, we first infer whether a miRNA regulates each common target by an ANFIS, which incorporates their sequences and known miRNA-target relationships to output a sequence score. Next, an FIS incorporates the Stage 1 fuzzy score, Stage 2 sequence score and gene expression correlation score of a miRNA-target pair to determine whether TF-miRNA coregulation exists. We collected 54 (8) TF-miRNA-target triples validated in ER-positive (ER-negative) breast cancer cell lines in the same article, and they were used as positives. Negative examples were constructed for Stage 1 (Stage 2) by pairing TFs (miRNAs) with human housekeeping genes found in the literature; both positives and negatives were used to train ANFISs in the training step. This two-stage fizzy algorithm was applied to predict 54 (8) TF-miRNA coregulation triples in ER-positive (ER-negative) human breast cancer cell lines, and

  6. MicroRNAs in colorectal cancer as markers and targets: Recent advances

    OpenAIRE

    Ye, Jing-jia; Cao, Jiang

    2014-01-01

    MicroRNAs are evolutionarily conserved small non-coding RNA molecules encoded by eukaryotic genomic DNA, and function in post-transcriptional regulation of gene expression via base-pairing with complementary sequences in target mRNAs, resulting in translational repression or degradation of target mRNAs. They represent one of the major types of epigenetic modification and play important roles in all aspects of cellular activities. Altered expression of microRNAs has been found in various human...

  7. Performance Comparison of Digital microRNA Profiling Technologies Applied on Human Breast Cancer Cell Lines

    OpenAIRE

    Knutsen, Erik; Fiskaa, Tonje; Ursvik, Anita; Jørgensen, Tor Erik; Perander, maria; Lund, Eiliv; Seternes, Ole Morten; Johansen, Steinar

    2013-01-01

    MicroRNA profiling represents an important first-step in deducting individual RNA-based regulatory function in a cell, tissue, or at a specific developmental stage. Currently there are several different platforms to choose from in order to make the initial miRNA profiles. In this study we investigate recently developed digital microRNA high-throughput technologies. Four different platforms were compared including next generation SOLiD ligation sequencing and Illumina HiSeq sequencing, hybr...

  8. MicroRNAs: From Female Fertility, Germ Cells, and Stem Cells to Cancer in Humans

    OpenAIRE

    Irma Virant-Klun; Anders Ståhlberg; Mikael Kubista; Thomas Skutella

    2016-01-01

    MicroRNAs are a family of naturally occurring small noncoding RNA molecules that play an important regulatory role in gene expression. They are suggested to regulate a large proportion of protein encoding genes by mediating the translational suppression and posttranscriptional control of gene expression. Recent findings show that microRNAs are emerging as important regulators of cellular differentiation and dedifferentiation, and are deeply involved in developmental processes including human ...

  9. Downregulation of microRNA-132 by DNA hypermethylation is associated with cell invasion in colorectal cancer

    OpenAIRE

    Qin J; Ke J; Xu JF; Wang FR; Zhou YL; Jiang YS; Wang ZW

    2015-01-01

    Jun Qin, Jing Ke, Junfei Xu, Feiran Wang, Youlang Zhou, Yasu Jiang, Zhiwei Wang Department of General Surgery, Affiliated Hospital of Nantong University, Nantong, Jiangsu Province, People’s Republic of China Abstract: microRNAs (miRNAs) are small, noncoding RNAs that are involved in many biological processes, and aberrant regulation of miRNAs is always associated with cancer progression and development. Abnormal expression of miRNA-132 (miR-132) has been found in some types of can...

  10. Comparison of Serum MicroRNA21 and Tumor Markers in Diagnosis of Early Non-Small Cell Lung Cancer

    OpenAIRE

    Mingzhong Sun; Jiangxiang Song; Zhongwei Zhou; Rong Zhu; Hao Jin; Yuqiao Ji; Qiang Lu; Huixiang Ju

    2016-01-01

    Objective. To compare the clinical value of serum microRNA21 (miR21) and other tumor markers in early diagnosis of non-small cell lung cancer (NSCLC). Methods. Serums carcinoembryonic antigen (CEA), cytokeratin 19 fragment (CYFRA21-1), neuron-specific enolase (NSE), and miR21 were detected in 50 NSCLC cases and 60 healthy control individuals. Results. Average serums miR21, CEA, NSE, and CYFRA21-1 levels were significantly higher in the case group than in control group (P < 0.01). Analysis of ...

  11. Deep sequencing identifies deregulation of microRNAs involved with vincristine drug-resistance of colon cancer cells

    OpenAIRE

    Dong, Wei-Hua; Li, Qin; Zhang, Xiao-Yan; Guo, Qing; Li, Huizheng; Wang, Tian-Yun

    2015-01-01

    Background: Vincristine (VCR) is a chemical that is widely used in tumor therapy. While long-term use can make tumor cells resistant to VCR, the underlying mechanisms of this resistance are still unclear. Objective: This study aimed at investigating the role of microRNA (miRNA) in colon cancer drug resistance. Methods: HCT-8 colon carcinoma cells were cultured and treated with different VCR concentrations to establish an HCT-8/VCR resistant cell line. Whole-genome screens, HiSeq 2500 sequenci...

  12. MicroRNA degeneracy and pluripotentiality within a Lavallière-tie architecture confers robustness to gene expression networks.

    Science.gov (United States)

    Bhajun, Ricky; Guyon, Laurent; Gidrol, Xavier

    2016-08-01

    Modularity, feedback control, functional redundancy and bowtie architecture have been proposed as key factors that confer robustness to complex biological systems. MicroRNAs (miRNAs) are highly conserved but functionally dispensable. These antinomic properties suggest that miRNAs fine-tune gene expression rather than act as genetic switches. We synthesize published and unpublished data and hypothesize that miRNA pluripotentiality acts to buffer gene expression, while miRNA degeneracy tunes the expression of targets, thus providing robustness to gene expression networks. Furthermore, we propose a Lavallière-tie architecture by integrating signal transduction, miRNAs and protein expression data to model complex gene expression networks. PMID:27038488

  13. MicroRNA-10a is reduced in breast cancer and regulated in part through retinoic acid

    International Nuclear Information System (INIS)

    MicroRNAs (miRNAs) are short non-coding RNA molecules that play a critical role in mRNA cleavage and translational repression, and are known to be altered in many diseases including breast cancer. MicroRNA-10a (miR-10a) has been shown to be deregulated in various cancer types. The aim of this study was to investigate miR-10a expression in breast cancer and to further delineate the role of retinoids and thyroxine in regulation of miR-10a. Following informed patient consent and ethical approval, tissue samples were obtained during surgery. miR-10a was quantified in malignant (n = 103), normal (n = 30) and fibroadenoma (n = 35) tissues by RQ-PCR. Gene expression of Retinoic Acid Receptor beta (RARβ) and Thyroid Hormone receptor alpha (THRα) was also quantified in the same patient samples (n = 168). The in vitro effects of all-trans Retinoic acid (ATRA) and L-Thyroxine (T4) both individually and in combination, on miR-10a expression was investigated in breast cancer cell lines, T47D and SK-BR-3. The level of miR-10a expression was significantly decreased in tissues harvested from breast cancer patients (Mean (SEM) 2.1(0.07)) Log10 Relative Quantity (RQ)) compared to both normal (3.0(0.16) Log10 RQ, p < 0.001) and benign tissues (2.6(0.17) Log10 RQ, p < 0.05). The levels of both RARβ and THRα gene expression were also found to be decreased in breast cancer patients compared to controls (p < 0.001). A significant positive correlation was determined between miR-10a and RARβ (r = 0.31, p < 0.001) and also with THRα (r = 0.32, p < 0.001). In vitro stimulation assays revealed miR-10a expression was increased in both T47D and SK-BR-3 cells following addition of ATRA (2 fold (0.7)). While T4 alone did not stimulate miR-10a expression, the combination of T4 and ATRA was found to have a positive synergistic effect. The data presented supports a potential tumour suppressor role for miR-10a in breast cancer, and highlights retinoic acid as a positive regulator of the microRNA

  14. Serum microRNA expression patterns that predict early treatment failure in prostate cancer patients

    Science.gov (United States)

    Singh, Prashant K.; Preus, Leah; Hu, Qiang; Yan, Li; Long, Mark D.; Morrison, Carl D.; Nesline, Mary; Johnson, Candace S.; Koochekpour, Shahriar; Kohli, Manish; Liu, Song; Trump, Donald L.

    2014-01-01

    We aimed to identify microRNA (miRNA) expression patterns in the serum of prostate cancer (CaP) patients that predict the risk of early treatment failure following radical prostatectomy (RP). Microarray and Q-RT-PCR analyses identified 43 miRNAs as differentiating disease stages within 14 prostate cell lines and reflectedpublically available patient data. 34 of these miRNA were detectable in the serum of CaP patients. Association with time to biochemical progression was examined in a cohort of CaP patients following RP. A greater than two-fold increase in hazard of biochemical progression associated with altered expression of miR-103, miR-125b and miR-222 (p <.0008) in the serum of CaP patients. Prediction models based on penalized regression analyses showed that the levels of the miRNAs and PSA together were better at detecting false positives than models without miRNAs, for similar level of sensitivity. Analyses of publically available data revealed significant and reciprocal relationships between changes in CpG methylation and miRNA expression patterns suggesting a role for CpG methylation to regulate miRNA. Exploratory validation supported roles for miR-222 and miR-125b to predict progression risk in CaP. The current study established that expression patterns of serum-detectable miRNAs taken at the time of RP are prognostic for men who are at risk of experiencing subsequent early biochemical progression. These non-invasive approaches could be used to augment treatment decisions. PMID:24583788

  15. MicroRNA-139 suppresses proliferation in luminal type breast cancer cells by targeting Topoisomerase II alpha

    International Nuclear Information System (INIS)

    The classification of molecular subtypes of breast cancer improves the prognostic accuracy and therapeutic benefits in clinic. However, because of the complexity of breast cancer, more biomarkers and functional molecules need to be explored. Here, analyzing the data in a huge cohort of breast cancer patients, we found that Topoisomerase II alpha (TOP2a), an important target of chemotherapy is a biomarker for prognosis in luminal type breast cancer patients, but not in basal like or HER2 positive breast cancer patients. We identified that miR-139, a previous reported anti-metastatic microRNA targets 3’-untranslated region (3′UTR) of TOP2a mRNA. Further more, we revealed that the forced expression of miR-139 reduces the TOP2a expression at both mRNA and protein levels. And our functional experiments showed that the ectopic expression of miR-139 remarkably inhibits proliferation in luminal type breast cancer cells, while exogenous TOP2a expression could rescue inhibition of cell proliferation mediated by miR-139. Collectively, our present study demonstrates the miR-139-TOP2a regulatory axis is important for proliferation in luminal type breast cancer cells. This functional link may help us to further understand the specificity of subtypes of breast cancer and optimize the strategy of cancer treatment. - Highlights: • High levels of TOP2a expression are closely associated with poor prognosis in luminal type breast cancer patients. • TOP2a is a novel target of miR-139. • Overexpression of miR-139 inhibits proliferation in luminal type breast cancer cells. • TOP2a is essential for miR-139-induced growth arrest in luminal type breast cancer cells

  16. MicroRNA-139 suppresses proliferation in luminal type breast cancer cells by targeting Topoisomerase II alpha

    Energy Technology Data Exchange (ETDEWEB)

    Hua, Wei [Department of Obstetrics and Gynecology, Xijing Hospital, Fourth Military Medical University, Xi' an 710032 (China); State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, Fourth Military Medical University, 710032 Xi' an (China); Sa, Ke-Di; Zhang, Xiang; Jia, Lin-Tao; Zhao, Jing [State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, Fourth Military Medical University, 710032 Xi' an (China); Yang, An-Gang [State Key Laboratory of Cancer Biology, Department of Immunology, Fourth Military Medical University, 710032 Xi' an (China); Zhang, Rui, E-mail: ruizhang@fmmu.edu.cn [State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, Fourth Military Medical University, 710032 Xi' an (China); Fan, Jing, E-mail: jingfan@fmmu.edu.cn [Department of Vascular and Endocrine Surgery, Xijing Hospital, Fourth Military Medical University, Xi' an 710032 (China); Bian, Ka, E-mail: kakamax85@hotmail.com [State Key Laboratory of Cancer Biology, Department of Immunology, Fourth Military Medical University, 710032 Xi' an (China); Department of Otolaryngology, Tangdu Hospital, Fourth Military Medical University, Xi' an 710038 (China)

    2015-08-07

    The classification of molecular subtypes of breast cancer improves the prognostic accuracy and therapeutic benefits in clinic. However, because of the complexity of breast cancer, more biomarkers and functional molecules need to be explored. Here, analyzing the data in a huge cohort of breast cancer patients, we found that Topoisomerase II alpha (TOP2a), an important target of chemotherapy is a biomarker for prognosis in luminal type breast cancer patients, but not in basal like or HER2 positive breast cancer patients. We identified that miR-139, a previous reported anti-metastatic microRNA targets 3’-untranslated region (3′UTR) of TOP2a mRNA. Further more, we revealed that the forced expression of miR-139 reduces the TOP2a expression at both mRNA and protein levels. And our functional experiments showed that the ectopic expression of miR-139 remarkably inhibits proliferation in luminal type breast cancer cells, while exogenous TOP2a expression could rescue inhibition of cell proliferation mediated by miR-139. Collectively, our present study demonstrates the miR-139-TOP2a regulatory axis is important for proliferation in luminal type breast cancer cells. This functional link may help us to further understand the specificity of subtypes of breast cancer and optimize the strategy of cancer treatment. - Highlights: • High levels of TOP2a expression are closely associated with poor prognosis in luminal type breast cancer patients. • TOP2a is a novel target of miR-139. • Overexpression of miR-139 inhibits proliferation in luminal type breast cancer cells. • TOP2a is essential for miR-139-induced growth arrest in luminal type breast cancer cells.

  17. Decoding network dynamics in cancer

    DEFF Research Database (Denmark)

    Linding, Rune

    2014-01-01

    models through computational integration of systematic, large-scale, high-dimensional quantitative data sets. I will review our latest advances in methods for exploring phosphorylation networks. In particular I will discuss how the combination of quantitative mass-spectrometry, systems......-genetics and computational algorithms (NetworKIN [Linding et al. Cell 2007] and NetPhorest [Miller et al. Science Signaling 2008]) made it possible for us to derive systems-level models of JNK and EphR signalling networks [Bakal et al. Science 2008, Jørgensen et al. Science 2009]. I shall discuss work we have done......Biological systems are composed of highly dynamic and interconnected molecular networks that drive biological decision processes. The goal of network biology is to describe, quantify and predict the information flow and functional behaviour of living systems in a formal language...

  18. Identifying Network Perturbation in Cancer.

    OpenAIRE

    Maxim Grechkin; Logsdon, Benjamin A.; Gentles, Andrew J.; Su-In Lee

    2016-01-01

    We present a computational framework, called DISCERN (DIfferential SparsE Regulatory Network), to identify informative topological changes in gene-regulator dependence networks inferred on the basis of mRNA expression datasets within distinct biological states. DISCERN takes two expression datasets as input: an expression dataset of diseased tissues from patients with a disease of interest and another expression dataset from matching normal tissues. DISCERN estimates the extent to which each ...

  19. Identifying Network Perturbation in Cancer

    OpenAIRE

    Grechkin, Maxim; Logsdon, Benjamin A.; Gentles, Andrew J.; Lee, Su-In

    2016-01-01

    We present a computational framework, called DISCERN (DIfferential SparsE Regulatory Network), to identify informative topological changes in gene-regulator dependence networks inferred on the basis of mRNA expression datasets within distinct biological states. DISCERN takes two expression datasets as input: an expression dataset of diseased tissues from patients with a disease of interest and another expression dataset from matching normal tissues. DISCERN estimates the extent to which each ...

  20. Novel circulating microRNA signature as a potential non-invasive multi-marker test in ER-positive early-stage breast cancer

    DEFF Research Database (Denmark)

    Kodahl, Annette R; Lyng, Maria Bibi; Binder, Harald;

    2014-01-01

    specific algorithm based on the 9 miRNA signature, the risk for future individuals can be predicted. Since microRNAs are highly stable in blood components, this signature might be useful in the development of a blood-based multi-marker test to improve early detection of breast cancer. Such a test could......INTRODUCTION: There are currently no highly sensitive and specific minimally invasive biomarkers for detection of early-stage breast cancer. MicroRNAs (miRNAs) are present in the circulation and may be unique biomarkers for early diagnosis of human cancers. The aim of this study was to investigate...... the differential expression of miRNAs in the serum of breast cancer patients and healthy controls. METHODS: Global miRNA analysis was performed on serum from 48 patients with ER-positive early-stage breast cancer obtained at diagnosis (24 lymph node-positive and 24 lymph node-negative) and 24 age...

  1. Changes in circulating microRNAs after radiochemotherapy in head and neck cancer patients

    International Nuclear Information System (INIS)

    Circulating microRNAs (miRNAs) are easily accessible and have already proven to be useful as prognostic markers in cancer patients. However, their origin and function in the circulation is still under discussion. In the present study we analyzed changes in the miRNAs in blood plasma of head and neck squamous cell carcinoma (HNSCC) patients in response to radiochemotherapy and compared them to the changes in a cell culture model of primary HNSCC cells undergoing simulated anti-cancer therapy. MiRNA-profiles were analyzed by qRT-PCR arrays in paired blood plasma samples of HNSCC patients before therapy and after two days of treatment. Candidate miRNAs were validated by single qRT-PCR assays. An in vitro radiochemotherapy model using primary HNSCC cell cultures was established to test the possible tumor origin of the circulating miRNAs. Microarray analysis was performed on primary HNSCC cell cultures followed by validation of deregulated miRNAs via qRT-PCR. Unsupervised clustering of the expression profiles using the six most regulated miRNAs (miR-425-5p, miR-21-5p, miR-106b-5p, miR-590-5p, miR-574-3p, miR-885-3p) significantly (p = 0.012) separated plasma samples collected prior to treatment from plasma samples collected after two days of radiochemotherapy. MiRNA profiling of primary HNSCC cell cultures treated in vitro with radiochemotherapy revealed differentially expressed miRNAs that were also observed to be therapy-responsive in blood plasma of the patients (miR-425-5p, miR-21-5p, miR-106b-5p, miR-93-5p) and are therefore likely to stem from the tumor. Of these candidate marker miRNAs we were able to validate by qRT-PCR a deregulation of eight plasma miRNAs as well as miR-425-5p and miR-93-5p in primary HNSCC cultures after radiochemotherapy. Changes in the abundance of circulating miRNAs during radiochemotherapy reflect the therapy response of primary HNSCC cells after an in vitro treatment. Therefore, the responsive miRNAs (miR-425-5p, miR-93-5p) may represent

  2. A Comprehensive Meta-Analysis of MicroRNAs for Predicting Colorectal Cancer.

    Science.gov (United States)

    Yan, Lin; Zhao, Wenhua; Yu, Haihua; Wang, Yansen; Liu, Yuanshui; Xie, Chao

    2016-03-01

    Colorectal cancer (CRC) has been defined as a common malignancy due to its prevailing incidence in both males and females. Recently, the intrinsic value of microRNAs (miRNAs) with respect to early cancer diagnosis has been contentious as the diagnostic accuracy of miRNAs significantly varied across different studies. As a result of this, this pioneer meta-analysis was proposed to address this issue.Qualified studies were obtained through electronic systematical searching in Medline, Embase, and PubMed. On the basis of the random-effects model, we calculated the pooled sensitivity (SEN), specificity (SPE), and area under the receiver operating characteristics curve (AUC) to assess the diagnostic accuracy of miRNAs. Subgroup analysis and meta-regression were implemented to determine how different confounding factors affect the overall diagnostic accuracy which were considered important sources of heterogeneity. All the statistical analyses were conducted with R 3.2.1 software.We incorporated 103 studies from 36 articles with a total of 3124 CRC patients and 2579 healthy individuals. MiRNAs have a good performance with the following pooled estimates: SEN = 0.769 (95% CI = 0.733-0.802), SPE = 0.806 (95% CI = 0.781-0.829), AUC = 0.857, and partial AUC = 0.773. As suggested by subgroup analyses and meta-regression, multiple miRNAs appeared to be more favorable than single miRNA (AUC: 0.918 > 0.813, partial AUC: 0.848 > 0.701, sensitivity = 0.853 > 0.718, specificity = 0.860 > 0.772). Compared with samples of plasma, blood, tissue, and feces, miRNA obtained from serum samples were more powerful for detecting CRC particularly in Asian.Our study provided exclusive evidence that multiple miRNAs extracted from serum samples had superior diagnostic performance over single miRNA for screening CRC. Therefore, this approach that is characterized by high specificity and noninvasive nature may assist in early diagnosis of CRC particularly in Asian

  3. Prognostic value of microRNA-203a expression in breast cancer.

    Science.gov (United States)

    Gomes, Bruno Costa; Martins, Manuela; Lopes, Paulina; Morujão, Inês; Oliveira, Mário; Araújo, António; Rueff, José; Rodrigues, António Sebastião

    2016-09-01

    Tumor heterogeneity and the poor outcome of breast cancer (BC) patients have led researchers to define new markers of this disease. In recent years, microRNA expression patterns have proven to be valuable disease indicators. The level of miR-203a, in particular, was shown to be altered in different types of cancer. The objective of the present study was to assess the relationship between miR-203a expression and clinicopathological features of BC in a Portuguese cohort. The expression levels of miR‑203a were analyzed in 109 formalin‑fixed paraffin-embedded paired normal and tumor tissue samples. Significant overexpression of miR‑203a in the tumor tissues was found (1.7-fold higher) compared to the expression in the normal adjacent tissues (p=0.003). In addition, several clinicopathological characteristics presented an association with higher miR-203a expression levels. Tumors with diameter ≤18.5 mm (1.5-fold; p=0.019), tumors positive for estrogen receptor (fold-change, 1.71; p=0.042), progesterone receptor (fold-change, 1.50; p=0.046) and negative for HER2 (fold-change, 1.50; p=0.016) and high Ki-67 index (fold-change, 2.60; p=0.024) presented a significant difference in miR-203a expression compared with adjacent normal tissues. Tumors without invasion of lymph nodes also presented higher expression of miR-203a (fold-change, 2.40; p=0.004). With regard to histological classification, ductal carcinomas in situ (fold-change, 2.20; p=0.028) and invasive carcinoma NOS (fold-change, 1.71; p=0.009) displayed significantly higher expression of miR-203a. Moreover, we found a significant downregulation of miR-203a with increased stage in invasive lobular carcinomas, suggesting that miR-203a could represent a potential marker to discriminate stages in invasive lobular carcinomas. PMID:27431784

  4. MicroRNAs Establish Robustness and Adaptability of a Critical Gene Network to Regulate Progenitor Fate Decisions during Cortical Neurogenesis

    Directory of Open Access Journals (Sweden)

    Tanay Ghosh

    2014-06-01

    Full Text Available Over the course of cortical neurogenesis, the transition of progenitors from proliferation to differentiation requires a precise regulation of involved gene networks under varying environmental conditions. In order to identify such regulatory mechanisms, we analyzed microRNA (miRNA target networks in progenitors during early and late stages of neurogenesis. We found that cyclin D1 is a network hub whose expression is miRNA-dosage sensitive. Experimental validation revealed a feedback regulation between cyclin D1 and its regulating miRNAs miR-20a, miR-20b, and miR-23a. Cyclin D1 induces expression of miR-20a and miR-20b, whereas it represses miR-23a. Inhibition of any of these miRNAs increases the developmental stage-specific mean and dynamic expression range (variance of cyclin D1 protein in progenitors, leading to reduced neuronal differentiation. Thus, miRNAs establish robustness and stage-specific adaptability to a critical dosage-sensitive gene network during cortical neurogenesis. Understanding such network regulatory mechanisms for key developmental events can provide insights into individual susceptibilities for genetically complex neuropsychiatric disorders.

  5. Identifying Cancer Subtypes from miRNA-TF-mRNA Regulatory Networks and Expression Data.

    Directory of Open Access Journals (Sweden)

    Taosheng Xu

    Full Text Available Identifying cancer subtypes is an important component of the personalised medicine framework. An increasing number of computational methods have been developed to identify cancer subtypes. However, existing methods rarely use information from gene regulatory networks to facilitate the subtype identification. It is widely accepted that gene regulatory networks play crucial roles in understanding the mechanisms of diseases. Different cancer subtypes are likely caused by different regulatory mechanisms. Therefore, there are great opportunities for developing methods that can utilise network information in identifying cancer subtypes.In this paper, we propose a method, weighted similarity network fusion (WSNF, to utilise the information in the complex miRNA-TF-mRNA regulatory network in identifying cancer subtypes. We firstly build the regulatory network where the nodes represent the features, i.e. the microRNAs (miRNAs, transcription factors (TFs and messenger RNAs (mRNAs and the edges indicate the interactions between the features. The interactions are retrieved from various interatomic databases. We then use the network information and the expression data of the miRNAs, TFs and mRNAs to calculate the weight of the features, representing the level of importance of the features. The feature weight is then integrated into a network fusion approach to cluster the samples (patients and thus to identify cancer subtypes. We applied our method to the TCGA breast invasive carcinoma (BRCA and glioblastoma multiforme (GBM datasets. The experimental results show that WSNF performs better than the other commonly used computational methods, and the information from miRNA-TF-mRNA regulatory network contributes to the performance improvement. The WSNF method successfully identified five breast cancer subtypes and three GBM subtypes which show significantly different survival patterns. We observed that the expression patterns of the features in some mi

  6. Regulation patterns in signaling networks of cancer

    Directory of Open Access Journals (Sweden)

    Kannabiran Nandakumar

    2010-11-01

    Full Text Available Abstract Background Formation of cellular malignancy results from the disruption of fine tuned signaling homeostasis for proliferation, accompanied by mal-functional signals for differentiation, cell cycle and apoptosis. We wanted to observe central signaling characteristics on a global view of malignant cells which have evolved to selfishness and independence in comparison to their non-malignant counterparts that fulfill well defined tasks in their sample. Results We investigated the regulation of signaling networks with twenty microarray datasets from eleven different tumor types and their corresponding non-malignant tissue samples. Proteins were represented by their coding genes and regulatory distances were defined by correlating the gene-regulation between neighboring proteins in the network (high correlation = small distance. In cancer cells we observed shorter pathways, larger extension of the networks, a lower signaling frequency of central proteins and links and a higher information content of the network. Proteins of high signaling frequency were enriched with cancer mutations. These proteins showed motifs of regulatory integration in normal cells which was disrupted in tumor cells. Conclusion Our global analysis revealed a distinct formation of signaling-regulation in cancer cells when compared to cells of normal samples. From these cancer-specific regulation patterns novel signaling motifs are proposed.

  7. Transcription factor CCAAT/enhancer binding protein alpha up-regulates microRNA let-7a-1 in lung cancer cells by direct binding

    OpenAIRE

    Lin, Yani; Zhao, Jian; Hu, Xiaoyan; Wang, Lina; Liang, Liming; Chen, Weiwen

    2016-01-01

    Aims The transcription factor CCAAT/enhancer binding protein α (C/EBPα) and microRNA (miRNA) let-7a-1 act as tumor suppressors in many types of cancers including lung cancer. In the present study, we aim to investigate whether let-7a-1 is a novel important target of C/EBPα in lung cancer cells. Methods The DNA sequence of the 2.1 kb let-7a-1 promoter was analyzed with MatInspector 4.1 (http://www.genomatix.de). Human lung cancer cell lines A549 and H1299, and human cervical cancer cell line H...

  8. Human colon cancer profiles show differential microRNA expression depending on mismatch repair status and are characteristic of undifferentiated proliferative states

    International Nuclear Information System (INIS)

    Colon cancer arises from the accumulation of multiple genetic and epigenetic alterations to normal colonic tissue. microRNAs (miRNAs) are small, non-coding regulatory RNAs that post-transcriptionally regulate gene expression. Differential miRNA expression in cancer versus normal tissue is a common event and may be pivotal for tumor onset and progression. To identify miRNAs that are differentially expressed in tumors and tumor subtypes, we carried out highly sensitive expression profiling of 735 miRNAs on samples obtained from a statistically powerful set of tumors (n = 80) and normal colon tissue (n = 28) and validated a subset of this data by qRT-PCR. Tumor specimens showed highly significant and large fold change differential expression of the levels of 39 miRNAs including miR-135b, miR-96, miR-182, miR-183, miR-1, and miR-133a, relative to normal colon tissue. Significant differences were also seen in 6 miRNAs including miR-31 and miR-592, in the direct comparison of tumors that were deficient or proficient for mismatch repair. Examination of the genomic regions containing differentially expressed miRNAs revealed that they were also differentially methylated in colon cancer at a far greater rate than would be expected by chance. A network of interactions between these miRNAs and genes associated with colon cancer provided evidence for the role of these miRNAs as oncogenes by attenuation of tumor suppressor genes. Colon tumors show differential expression of miRNAs depending on mismatch repair status. miRNA expression in colon tumors has an epigenetic component and altered expression that may reflect a reversion to regulatory programs characteristic of undifferentiated proliferative developmental states

  9. Coregulation of transcription factors and microRNAs in human transcriptional regulatory network

    OpenAIRE

    Chen Shui-Tein; Fuh Chiou-Shann; Chen Cho-Yi; Juan Hsueh-Fen; Huang Hsuan-Cheng

    2011-01-01

    Abstract Background MicroRNAs (miRNAs) are small RNA molecules that regulate gene expression at the post-transcriptional level. Recent studies have suggested that miRNAs and transcription factors are primary metazoan gene regulators; however, the crosstalk between them still remains unclear. Methods We proposed a novel model utilizing functional annotation information to identify significant coregulation between transcriptional and post-transcriptional layers. Based on this model, function-en...

  10. MicroRNA-100 regulates SW620 colorectal cancer cell proliferation and invasion by targeting RAP1B.

    Science.gov (United States)

    Peng, Hui; Luo, Jun; Hao, Hu; Hu, Jun; Xie, Shang-Kui; Ren, Donglin; Rao, Benqiang

    2014-05-01

    MicroRNAs (miRNAs) have been demonstrated to play important roles in tumorigenesis of human cancer. Fewer studies have explored the roles of miR-100 on human colorectal cancer cell proliferation and invasion. In this study, we utilized real-time PCR to verify whether miR-100 was downregulated in human colorectal cancer tissues compared with matched adjacent normal tissues. Functional studies demonstrated that ectopic expression of miR-100 inhabits cell growth and invasion and induce apoptosis, whereas knockdown of miR-100 yielded the reverse phenotype. Mechanistic studies reveal that miR-100 repressed the activity of a reporter gene fused to the 3'-untranslated region (3'-UTR) of RAP1B, whereas miR-100 silencing upregulated the expression of the reporter gene. Furthermore, we also detected that RAP1B mRNA was inversely expressed with miR-100 in colorectal cancer tissues. These data indicate that the miR-100 plays a tumor suppressor role by regulating colorectal cancer cell growth and invasion phenotype, and could serve as a potential maker for colorectal cancer therapy. PMID:24626817

  11. TanshinoneIIA ameliorates inflammatory microenvironment of colon cancer cells via repression of microRNA-155.

    Science.gov (United States)

    Tu, Jiajie; Xing, Yingying; Guo, Yongjian; Tang, Feng; Guo, Le; Xi, Tao

    2012-12-01

    TanshinoneIIA, an active component derived from a traditional Chinese medicine, has anti-inflammatory and anti-cancer effect. However, the mechanisms underlying the interaction between anti-inflammation and anti-cancer of TanshinoneIIA remain elusive. In the present study, a cell model of inflammation between macrophages and colon cancer cells was used. The results showed that TanshinoneIIA inhibited the proliferation of inflammation-related colon cancer cells HCT116 and HT-29 by decreasing the production of inflammatory cytokines tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6), which generated by macrophage RAW264.7 cell line. We identified Phosphatidylinositol-3, 4, 5-trisphosphate 5-phosphatase 1 (SHIP1) was a bona fide target of miR-155. TanshinoneIIA restored the down-regulated level of SHIP1 protein after lipopolysaccharide (LPS)-stimulation in RAW264.7 cells. MicroRNA-155 (miR-155) was up-regulated in macrophages, possibly due to the concomitant increase of PU.1, a transcriptional activator of miR-155, accounting for decreased SHIP1. Treatment with TanshinoneIIA prevented increased PU.1 and hence increased miR-155, whereas aspirin could not. These findings support that the interruption of signal conduction between activated macrophages and colon cancer cells could be considered as a new therapeutic strategy and miR-155 could be a potential target for the prevention of inflammation-related cancer. PMID:22982040

  12. Evaluation of cell-free urine microRNAs expression for the use in diagnosis of ovarian and endometrial cancers. A pilot study

    Czech Academy of Sciences Publication Activity Database

    Záveský, L.; Jandáková, E.; Turyna, R.; Langmeierová, L.; Weinberger, V.; Záveská Drábková, Lenka; Hůlková, M.; Hořínek, A.; Dušková, D.; Feyereisl, J.; Minář, L.; Kohoutová, M.

    2015-01-01

    Roč. 21, č. 4 (2015), s. 1027-1035. ISSN 1219-4956 Institutional support: RVO:67985939 Keywords : microRNA * ovarian cancer * mi92 * mi106b Subject RIV: EF - Botanics Impact factor: 1.855, year: 2014

  13. Evaluation of cell-free urine microRNAs expression for the use in diagnosis of ovarian and endometrial cancers. A pilot study.

    Czech Academy of Sciences Publication Activity Database

    Záveský, L.; Jandáková, E.; Turyna, R.; Langmeierová, L.; Weinberger, V.; Záveská Drábková, Lenka; Hůlková, M.; Hořínek, A.; Dušková, D.; Feyereisl, J.; Minar, L.; Kohoutová, M.

    2015-01-01

    Roč. 21, č. 4 (2015), s. 1027-1035. ISSN 1219-4956 Institutional support: RVO:68378050 Keywords : microRNA * ovarian cancer * mi92 * mi106b Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 1.855, year: 2014

  14. MicroRNA-320a suppresses human colon cancer cell proliferation by directly targeting {beta}-catenin

    Energy Technology Data Exchange (ETDEWEB)

    Sun, Jian-Yong [State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, Fourth Military Medical University, 710032 Xi' an (China); State Key Laboratory of Cancer Biology, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, 710032 Xi' an (China); Huang, Yi [Department of Anesthesiology, Xijing Hospital, Fourth Military Medical University, 710032 Xi' an (China); Li, Ji-Peng [State Key Laboratory of Cancer Biology, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, 710032 Xi' an (China); Zhang, Xiang; Wang, Lei [State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, Fourth Military Medical University, 710032 Xi' an (China); Meng, Yan-Ling [Department of Immunology, Fourth Military Medical University, 710032 Xi' an (China); Yan, Bo [State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, Fourth Military Medical University, 710032 Xi' an (China); Bian, Yong-Qian [State Key Laboratory of Cancer Biology, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, 710032 Xi' an (China); Zhao, Jing [State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, Fourth Military Medical University, 710032 Xi' an (China); Wang, Wei-Zhong, E-mail: weichang@fmmu.edu.cn [State Key Laboratory of Cancer Biology, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, 710032 Xi' an (China); and others

    2012-04-20

    Highlights: Black-Right-Pointing-Pointer miR-320a is downregulated in human colorectal carcinoma. Black-Right-Pointing-Pointer Overexpression of miR-320a inhibits colon cancer cell proliferation. Black-Right-Pointing-Pointer {beta}-Catenin is a direct target of miR-320a in colon cancer cells. Black-Right-Pointing-Pointer miR-320a expression inversely correlates with mRNA expression of {beta}-catenin's target genes in human colon carcinoma. -- Abstract: Recent profile studies of microRNA (miRNA) expression have documented a deregulation of miRNA (miR-320a) in human colorectal carcinoma. However, its expression pattern and underlying mechanisms in the development and progression of colorectal carcinoma has not been elucidated clearly. Here, we performed real-time PCR to examine the expression levels of miR-320a in colon cancer cell lines and tumor tissues. And then, we investigated its biological functions in colon cancer cells by a gain of functional strategy. Further more, by the combinational approaches of bioinformatics and experimental validation, we confirmed target associations of miR-320a in colorectal carcinoma. Our results showed that miR-320a was frequently downregulated in cancer cell lines and colon cancer tissues. And we demonstrated that miR-320a restoration inhibited colon cancer cell proliferation and {beta}-catenin, a functionally oncogenic molecule was a direct target gene of miR-320a. Finally, the data of real-time PCR showed the reciprocal relationship between miR-320a and {beta}-catenin's downstream genes in colon cancer tissues. These findings indicate that miR-320a suppresses the growth of colon cancer cells by directly targeting {beta}-catenin, suggesting its application in prognosis prediction and cancer treatment.

  15. MicroRNA-320a suppresses human colon cancer cell proliferation by directly targeting β-catenin

    International Nuclear Information System (INIS)

    Highlights: ► miR-320a is downregulated in human colorectal carcinoma. ► Overexpression of miR-320a inhibits colon cancer cell proliferation. ► β-Catenin is a direct target of miR-320a in colon cancer cells. ► miR-320a expression inversely correlates with mRNA expression of β-catenin’s target genes in human colon carcinoma. -- Abstract: Recent profile studies of microRNA (miRNA) expression have documented a deregulation of miRNA (miR-320a) in human colorectal carcinoma. However, its expression pattern and underlying mechanisms in the development and progression of colorectal carcinoma has not been elucidated clearly. Here, we performed real-time PCR to examine the expression levels of miR-320a in colon cancer cell lines and tumor tissues. And then, we investigated its biological functions in colon cancer cells by a gain of functional strategy. Further more, by the combinational approaches of bioinformatics and experimental validation, we confirmed target associations of miR-320a in colorectal carcinoma. Our results showed that miR-320a was frequently downregulated in cancer cell lines and colon cancer tissues. And we demonstrated that miR-320a restoration inhibited colon cancer cell proliferation and β-catenin, a functionally oncogenic molecule was a direct target gene of miR-320a. Finally, the data of real-time PCR showed the reciprocal relationship between miR-320a and β-catenin’s downstream genes in colon cancer tissues. These findings indicate that miR-320a suppresses the growth of colon cancer cells by directly targeting β-catenin, suggesting its application in prognosis prediction and cancer treatment.

  16. MicroRNA-155 deletion promotes tumorigenesis in the azoxymethane-dextran sulfate sodium model of colon cancer.

    Science.gov (United States)

    Velázquez, Kandy T; Enos, Reilly T; McClellan, Jamie L; Cranford, Taryn L; Chatzistamou, Ioulia; Singh, Udai P; Nagarkatti, Mitzi; Nagarkatti, Prakash S; Fan, Daping; Murphy, E Angela

    2016-03-15

    Clinical studies have linked microRNA-155 (miR-155) expression in the tumor microenvironment to poor prognosis. However, whether miR-155 upregulation is predictive of a pro- or antitumorigenic response is unclear, as the limited preclinical data available remain controversial. We examined miR-155 expression in tumor tissue from colon cancer patients. Furthermore, we investigated the role of this microRNA in proliferation and apoptosis, inflammatory processes, immune cell populations, and transforming growth factor-β/SMAD signaling in a chemically induced (azoxymethane-dextran sulfate sodium) mouse model of colitis-associated colon cancer. We found a higher expression of miR-155 in the tumor region than in nontumor colon tissue of patients with colon cancer. Deletion of miR-155 in mice resulted in a greater number of polyps/adenomas, an increased symptom severity score, a higher grade of epithelial dysplasia, and a decrease in survival. Surprisingly, these findings were associated with an increase in apoptosis in the normal mucosa, but there was no change in proliferation. The protumorigenic effects of miR-155 deletion do not appear to be driven solely by dysregulation of inflammation, as both genotypes had relatively similar levels of inflammatory mediators. The enhanced tumorigenic response in miR-155(-/-) mice was associated with alterations in macrophages and neutrophils, as markers for these populations were decreased and increased, respectively. Furthermore, we demonstrated a greater activation of the transforming growth factor-β/SMAD pathway in miR-155(-/-) mice, which was correlated with the increased tumorigenesis. Given the multiple targets of miR-155, careful evaluation of its role in tumorigenesis is necessary prior to any consideration of its potential as a biomarker and/or therapeutic target in colon cancer. PMID:26744471

  17. Association between microRNA polymorphisms and cancer risk based on the findings of 66 case-control studies.

    Directory of Open Access Journals (Sweden)

    Xiao Pin Ma

    Full Text Available MicroRNAs (miRNAs are small non-coding RNA molecules, which participate in diverse biological processes and may regulate tumor suppressor genes or oncogenes. Single nucleotide polymorphisms (SNPs in miRNA may contribute to diverse functional consequences, including cancer development, by altering miRNA expression. Numerous studies have shown the association between miRNA SNPs and cancer risk; however, the results are generally debatable and inconclusive, mainly due to limited statistical power. To assess the relationship between the five most common SNPs (miR-146a rs2910164, miR-196a2 rs11614913, miR-499 rs3746444, miR-149 rs2292832, and miR-27a rs895919 and the risk cancer development, we performed a meta-analysis of 66 published case-control studies. Crude odds ratios at 95% confidence intervals were used to investigate the strength of the association. No association was observed between rs2910164 and cancer risk in the overall group. However, in stratified analysis, we found that either the rs2910164 C allele or the CC genotype was protective against bladder cancer, prostate cancer, cervical cancer, and colorectal cancer, whereas it was a risk factor for papillary thyroid carcinoma and squamous cell carcinoma of the head and neck (SCCHN. Further, rs11614913 was found to be significantly associated with decreased cancer risk, in particular, for bladder cancer, gastric cancer, and SCCHN. For miR-499, a significant association was found between the rs3746444 polymorphism and cancer risk in pooled analysis. In subgroup analysis, similar results were mainly observed for breast cancer. Finally, no association was found between rs2292832 and rs895919 polymorphisms and cancer risk in the overall group and in stratified analysis. In summary, miR-196a2 rs11614913, miR-146a rs2910164, and miR-499 rs3746444 are risk factors for cancer development, whereas mir-149 rs2292832 and miR-27a rs895919 are not associated with cancer risk.

  18. Programmed cell death 4 (PDCD4) is an important functional target of the microRNA miR-21 in breast cancer cells

    DEFF Research Database (Denmark)

    Frankel, Lisa; Christoffersen, Nanna R; Jacobsen, Anders; Lindow, Morten; Krogh, Anders; Lund, Anders Henrik

    2008-01-01

    MicroRNAs are emerging as important regulators of cancer-related processes. The miR-21 microRNA is overexpressed in a wide variety of cancers and has been causally linked to cellular proliferation, apoptosis, and migration. Inhibition of mir-21 in MCF-7 breast cancer cells causes reduced cell...... growth. Using array expression analysis of MCF-7 cells depleted of miR-21, we have identified mRNA targets of mir-21 and have shown a link between miR-21 and the p53 tumor suppressor protein. We furthermore found that the tumor suppressor protein Programmed Cell Death 4 (PDCD4) is regulated by miR-21 and...... demonstrated that PDCD4 is a functionally important target for miR-21 in breast cancer cells....

  19. MicroRNA-744 inhibited cervical cancer growth and progression through apoptosis induction by regulating Bcl-2.

    Science.gov (United States)

    Chen, Xiao-Fang; Liu, Yun

    2016-07-01

    Growing evidence suggests that microRNA plays an essential role in the development and metastasis of many tumor progressions, including cervical cancer. Aberrant miR-744 expression has been indicated in many growth of tumor, the mechanism of miR-744 inhibits both the proliferation and metastatic ability for cervical cancer remains unclear. Accumulating evidences reported that Bcl-2 signal pathway plays an important role in the cellular process, such as apoptosis, cell growth and proliferation. The goal of this study was to identify miR-744 that could inhibit the growth, migration, invasion, proliferation and metastasis of gastric cancer through targeting Bcl-2 expression. Real-time PCR (RT-qPCR) was used to quantify miR-744 expression in vitro and vivo experiments. The biological functions of miR-744 were determined via cell proliferation. Our study indicated that miR-744 targeted on Bcl-2, which leads to the inactivation of apoptosis signaling and the cell proliferation of cervical cancer cells, ameliorating cervical cancer growth and progression. In addition, both up-regulation of miR-744 and down-regulation of Bcl-2 could stimulate Caspase-3 expression, promoting apoptosis of cervical cancer cells. Therefore, our research revealed the mechanistic links between miR-744 and Bcl-2 in the pathogenesis of cervical cancer through modulation of Caspase-3, leading to the inhibition of cervical cancer cell growth. And targeting miR-744 could be served as a novel strategy for future cervical cancer therapy clinically. PMID:27261616

  20. MicroRNA expression profile associated with response to neoadjuvant chemoradiotherapy in locally advanced rectal cancer patients

    International Nuclear Information System (INIS)

    Rectal cancer accounts for approximately one third of all colorectal cancers (CRC), which belong among leading causes of cancer deaths worldwide. Standard treatment for locally advanced rectal cancer (cT3/4 and/or cN+) includes neoadjuvant chemoradiotherapy with fluoropyrimidines (capecitabine or 5-fluorouracil) followed by radical surgical resection. Unfortunately, a significant proportion of tumors do not respond enough to the neoadjuvant treatment and these patients are at risk of relapse. MicroRNAs (miRNAs) are small non-coding RNAs playing significant roles in the pathogenesis of many cancers including rectal cancer. MiRNAs could present the new predictive biomarkers for rectal cancer patients. We selected 20 patients who underwent neoadjuvant chemoradiotherapy for advanced rectal cancer and whose tumors were classified as most sensitive or resistant to the treatment. These two groups were compared using large-scale miRNA expression profiling. Expression levels of 8 miRNAs significantly differed between two groups. MiR-215, miR-190b and miR-29b-2* have been overexpressed in non-responders, and let-7e, miR-196b, miR-450a, miR-450b-5p and miR-99a* have shown higher expression levels in responders. Using these miRNAs 9 of 10 responders and 9 of 10 non-responders (p < 0.05) have been correctly classified. Our pilot study suggests that miRNAs are part of the mechanisms that are involved in response of rectal cancer to the chemoradiotherapy and that miRNAs may be promising predictive biomarkers for such patients. In most miRNAs we identified (miR-215, miR-99a*, miR-196b, miR-450b-5p and let-7e), the connection between their expression and radioresistance or chemoresistance to inhibitors of thymidylate synthetase was already established

  1. MicroRNA miR-16-1 regulates CCNE1 (cyclin E1) gene expression in human cervical cancer cells

    OpenAIRE

    Zubillaga-Guerrero, Ma Isabel; Alarcón-Romero, Luz Del Carmen; Illades-Aguiar, Berenice; Flores-Alfaro, Eugenia; Bermúdez-Morales, Víctor Hugo; Deas, Jessica; Peralta-Zaragoza, Oscar

    2015-01-01

    MicroRNAs are involved in diverse biological processes through regulation of gene expression. The microRNA profile has been shown to be altered in cervical cancer (CC). MiR-16-1 belongs to the miR-16 cluster and has been implicated in various aspects of carcinogenesis including cell proliferation and regulation of apoptosis; however, its function and molecular mechanism in CC is not clear. Cyclin E1 (CCNE1) is a positive regulator of the cell cycle that controls the transition of cells from G...

  2. microRNAs are Stable in Formalin-Fixed Paraffin-Embedded Archival Tissue Specimens of Colorectal Cancers Stored for up to 28 Years

    OpenAIRE

    Bovell, Liselle; Shanmugam, Chandrakumar; Katkoori, Venkat R.; Zhang, Bin; Vogtmann, Emily; Grizzle, William E.; Manne, Upender

    2012-01-01

    MicroRNAs (miRNAs) have prognostic and therapeutic value for colorectal cancers (CRCs). Although formalin-fixed paraffin-embedded (FFPE) tissues are available for biomarker studies, the stability of miRNAs in these tissues stored for long periods (>20 years) is unknown. The present effort involved analysis of 345 FFPE CRC tissues, stored for 6 to 28 years (1982-2004), for the expression of six miRNAs (miR-20a, miR-21, miR-106a, miR-181b, miR-203, and miR-324-5p) using TaqMan® microRNA assays ...

  3. A New Role for an Old Drug: Metformin Targets MicroRNAs in Treating Diabetes and Cancer.

    Science.gov (United States)

    Zhou, Joseph Yi; Xu, Biao; Li, Lixin

    2015-09-01

    MicroRNAs (miRNAs) are a family of short, noncoding, 19-23 base pair RNA molecules. Due to their unique role in gene regulation in various tissues, miRNAs play important roles in regulating insulin secretion, metabolic disease, and cancer biology. Emerging evidence demonstrates that miRNAs could also be novel diagnostic markers for a variety of disease states. Additionally, miRNAs have been found to function either as oncogenes, or tumor suppressor genes in cerian cancers. An increasing number of studies have been conducted investigating new drugs targeting miRNAs as a potential anticancer therapy. Metformin is the most widely prescribed medication for treating Type 2 diabetes (T2D). Recent clinical data suggests that metformin impacts the miRNA profile in T2D subjects. Most excitingly, studies have found that metformin is protective against cancer. The anticancer activity of metformin is mediated through a direct regulation of miRNAs, which further modulates several downstream genes in metabolic or preoncogenic pathways. These miRNAs are, therefore, prospective therapeutic targets for treating diabetes and cancer which is the topic of this review. Further study on the regulation of miRNAs by metformin could result in novel therapeutic strategies for recurrent or drug-esistant cancer, and as part of combinatorial approaches with conventional anticancer therapies. PMID:26936407

  4. microRNA-146a inhibits G protein-coupled receptor-mediated activation of NF-κB by targeting CARD10 and COPS8 in gastric cancer

    DEFF Research Database (Denmark)

    Crone, Stephanie Geisler; Jacobsen, Anders; Federspiel, Birgitte;

    2012-01-01

    Gastric cancer is the second most common cause of cancer-related death in the world. Inflammatory signals originating from gastric cancer cells are important for recruiting inflammatory cells and regulation of metastasis of gastric cancer. Several microRNAs (miRNA) have been shown to be involved ...

  5. MicroRNAs in Ewing Sarcoma

    OpenAIRE

    PaulJedlicka; LayneDylla

    2013-01-01

    MicroRNAs have emerged recently as important regulators of gene expression in the cell. Frequently dysregulated in cancer, microRNAs have shed new light on molecular mechanisms of oncogenesis, and have generated substantial interest as biomarkers, and novel therapeutic agents and targets. Recently, a number of studies have examined microRNA biology in Ewing Sarcoma. Findings indicate that alterations in microRNA expression in Ewing Sarcoma are widespread, involve both EWS/Ets oncogenic fusion...

  6. Noninvasive visualization of microRNA-16 in the chemoresistance of gastric cancer using a dual reporter gene imaging system.

    Directory of Open Access Journals (Sweden)

    Fu Wang

    Full Text Available MicroRNAs (miRNAs have been implicated to play a central role in the development of drug resistance in a variety of malignancies. However, many studies were conducted at the in vitro level and could not provide the in vivo information on the functions of miRNAs in the anticancer drug resistance. Here, we introduced a dual reporter gene imaging system for noninvasively monitoring the kinetic expression of miRNA-16 during chemoresistance in gastric cancer both in vitro and in vivo. Human sodium iodide symporter (hNIS and firefly luciferase (Fluc genes were linked to form hNIS/Fluc double fusion reporter gene and then generate human gastric cancer cell line NF-3xmir16 and its multidrug resistance cell line NF-3xmir16/VCR. Radioiodide uptake and Fluc luminescence signals in vitro correlated well with viable cell numbers. The luciferase activities and radioiodide uptake in NF-3xmir16 cells were remarkably repressed by exogenous or endogenous miRNA-16. The NF-3xmir16/VCR cells showed a significant increase of (131I uptake and luminescence intensity compared to NF-3xmir16 cells. The radioactivity from in vivo (99mTc-pertechnetate imaging and the intensity from bioluminescence imaging were also increased in NF-3xmir16/VCR compared with that in NF-3xmir16 tumor xenografts. Furthermore, using this reporter gene system, we found that etoposide (VP-16 and 5-fluorouracil (5-FU activated miRNA-16 expression in vitro and in vivo, and the upregulation of miRNA-16 is p38MAPK dependent but NF-κB independent. This dual imaging reporter gene may be served as a novel tool for in vivo imaging of microRNAs in the chemoresistance of cancers, as well as for early detection and diagnosis in clinic.

  7. Identification of colorectal cancer-restricted microRNAs and their target genes based on high-throughput sequencing data

    Directory of Open Access Journals (Sweden)

    Chang J

    2016-03-01

    Full Text Available Jing Chang, Liya Huang, Qing Cao, Fang Liu Department of Gerontology, Xinhua Hospital Affiliated to Jiaotong University School of Medicine, Shanghai, People’s Republic of China Abstract: To identify potential key microRNAs (miRNAs and their target genes for colorectal cancer (CRC. High-throughput sequencing data of miRNA expression and gene expression (ID: GSE46622 were downloaded from Gene Expression Omnibus, including matched colon tumor, normal colon epithelium, and liver metastasis tissues from eight CRC patients. Paired t-test and NOISeq separately were utilized to identify differentially expressed miRNAs (DE-miRNAs and genes. Then, target genes with differential expression and opposite expression trends were identified for DE-miRNAs. Combined with tumor suppressor gene, tumor-associated gene, and TRANSFAC databases, CRC-restricted miRNAs were screened out based on miRNA-target pairs. Compared with normal tissues, there were 56 up- and 37 downregulated miRNAs in metastasis tissues, as well as eight up- and 30 downregulated miRNAs in tumor tissues. miRNA-1 was downregulated in tumor and metastasis tissues, while its target oncogenes TWIST1 and GATA4 were upregulated. Besides, miRNA-let-7f-1-3p was downregulated in tumor tissues, which also targeted TWIST1. In addition, miRNA-133b and miRNA-4458 were downregulated in tumor tissues, while their common target gene DUSP9 was upregulated. Conversely, miRNA-450b-3p was upregulated in metastasis tissues, while its target tumor suppressor gene CEACAM7 showed downregulation. The identified CRC-restricted miRNAs might be implicated in cancer progression via their target genes, suggesting their potential usage in CRC treatment. Keywords: colorectal cancer, differentially expressed microRNAs, differentially expressed genes, oncogenes, tumor suppressor genes

  8. Functional microRNAs in Alzheimer’s disease and cancer: differential regulation of common mechanisms and pathways

    Directory of Open Access Journals (Sweden)

    Kelly N Holohan

    2013-01-01

    Full Text Available Two of the main research priorities in the United States are cancer and neurodegenerative diseases, which are attributed to abnormal patterns of cellular behavior. MicroRNAs (miRNA have been implicated as regulators of cellular metabolism, and thus are an active topic of investigation in both disease areas. There is presently a more extensive body of work on the role of miRNAs in cancer compared to neurodegenerative diseases, and therefore it may be useful to examine whether there is any concordance between the functional roles of miRNAs in these diseases. As a case study, the roles of miRNAs in Alzheimer’s disease (AD and their functions in various cancers will be compared. A number of miRNA expression patterns are altered in individuals with AD compared with healthy older adults. Among these, some have also been shown to correlate with neuropathological changes including plaque and tangle accumulation, as well as expression levels of other molecules known to be involved in disease pathology. Importantly, these miRNAs have also been shown to have differential expression and or functional roles in various types of cancer. To examine possible intersections between miRNA functions in cancer and AD, we review the current literature on eight of these miRNAs in cancer and AD, focusing on their roles in known biological pathways. We propose a pathway-driven model in which some molecular processes show an inverse relationship between cancer and neurodegenerative disease (e.g., proliferation and apoptosis whereas others are more parallel in their activity (e.g., immune activation and inflammation. A critical review of these and other molecular mechanisms in cancer may shed light on the pathophysiology of AD, and highlight key areas for future research. Conclusions from this work may be extended to other neurodegenerative diseases for which some molecular pathways have been identified but which have not yet been extensively researched for mi

  9. Deregulation of MicroRNA-375 inhibits cancer proliferation migration and chemosensitivity in pancreatic cancer through the association of HOXB3

    Science.gov (United States)

    Yang, Dejun; Yan, Ronglin; Zhang, Xin; Zhu, Zhenxin; Wang, Changming; Liang, Chao; Zhang, Xin

    2016-01-01

    Background: The expression pattern and regulatory effect of microRNA-375 (miR-375) in human pancreatic cancer was explored. Methods: Gene expression of miR-375 was compared between pancreatic tumors and non-tumorous pancreatic tissues, as well as pancreatic cancer cell lines and normal epithelial cells. MiR-375 was downregulated in pancreatic cancer cell lines, Capan-1 and PANC-1 cells, to assess possible tumor suppressive effects on cancer proliferation, migration, cisplatin chemosensitivity and in vivo growth of tumor explant. The regulation of miR-375 on its target gene, homeobox B3 (HOXB3) gene, was assessed though luciferase activity assay and qRT-PCR. HOXB3 was also downregulated in Capan-1 and PANC-1 cells to assess its functional correlation with miR-375 on cancer regulation. Results: MiR-375 was upregulated in pancreatic tumors and pancreatic cancer cell lines. MiR-375 downregulation had tumor suppressive effects in Capan-1 and PANC-1 cells by reducing cancer proliferation & migration, increasing cisplatin sensitivity and inhibiting in vivo tumor explant growth. HOXB3 was directly bound by miR-375, and was negatively regulated by miR-375 in pancreatic cancer cells. Subsequent HOXB3 downregulation reversed the suppression of miR-375 downregulation on cancer proliferation, migration and cisplatin chemosensitivity in pancreatic cancer. Conclusion: MiR-375 is an oncogene in pancreatic cancer. Deregulation of miR-375 is inhibitory to the development of pancreatic cancer, and reversely regulated by HOXB3. PMID:27186281

  10. A Coregulatory Network of NR2F1 and microRNA-140

    OpenAIRE

    Chiang, David Y.; Cuthbertson, David W.; Ruiz, Fernanda R.; Li, Na; Pereira, Fred A.

    2013-01-01

    Background Both nuclear receptor subfamily 2 group F member 1 (NR2F1) and microRNAs (miRNAs) have been shown to play critical roles in the developing and functional inner ear. Based on previous studies suggesting interplay between NR2F1 and miRNAs, we investigated the coregulation between NR2F1 and miRNAs to better understand the regulatory mechanisms of inner ear development and functional maturation. Results Using a bioinformatic approach, we identified 11 potential miRNAs that might coregu...

  11. Silencing of ABCG2 by MicroRNA-3163 Inhibits Multidrug Resistance in Retinoblastoma Cancer Stem Cells.

    Science.gov (United States)

    Jia, Ming; Wei, Zhenhua; Liu, Peng; Zhao, Xiaoli

    2016-06-01

    To investigate the function and regulation mechanism of ATP-binding cassette, subfamily G, member 2 (ABCG2) in retinoblastoma cancer stem cells (RCSCs), a long-term culture of RCSCs from WERI-Rb1 cell line was successfully established based on the high expression level of ABCG2 on the surface of RCSCs. To further explore the molecular mechanism of ABCG2 on RCSCs, a microRNA that specifically targets ABCG2 was predicted. Subsequently, miR-3163 was selected and confirmed as the ABCG2-regulating microRNA. Overexpression of miR-3163 led to a significant decrease in ABCG2 expression. Additionally, ABCG2 loss-of-function induced anti-proliferation and apoptosis-promoting functions in RCSCs, and multidrug resistance to cisplatin, carboplatin, vincristine, doxorubicin, and etoposide was greatly improved in these cells. Our data suggest that miR-3163 has a significant impact on ABCG2 expression and can influence proliferation, apoptosis, and drug resistance in RCSCs. This work may provide new therapeutic targets for retinoblastoma. PMID:27247490

  12. Differential Network Analysis in Human Cancer Research

    Science.gov (United States)

    Gill, Ryan; Datta, Somnath; Datta, Susmita

    2016-01-01

    A complex disease like cancer is hardly caused by one gene or one protein singly. It is usually caused by the perturbation of the network formed by several genes or proteins. In the last decade several research teams have attempted to construct interaction maps of genes and proteins either experimentally or reverse engineer interaction maps using computational techniques. These networks were usually created under a certain condition such as an environmental condition, a particular disease, or a specific tissue type. Lately, however, there has been greater emphasis on finding the differential structure of the existing network topology under a novel condition or disease status to elucidate the perturbation in a biological system. In this review/tutorial article we briefly mention some of the research done in this area; we mainly illustrate the computational/statistical methods developed by our team in recent years for differential network analysis using publicly available gene expression data collected from a well known cancer study. This data includes a group of patients with acute lymphoblastic leukemia and a group with acute myeloid leukemia. In particular, we describe the statistical tests to detect the change in the network topology based on connectivity scores which measure the association or interaction between pairs of genes. The tests under various scores are applied to this data set to perform a differential network analysis on gene expression for human leukemia. We believe that, in the future, differential network analysis will be a standard way to view the changes in gene expression and protein expression data globally and these types of tests could be useful in analyzing the complex differential signatures. PMID:23530503

  13. Navigating cancer network attractors for tumor-specific therapy

    DEFF Research Database (Denmark)

    Creixell, Pau; Schoof, Erwin; Erler, Janine Terra;

    2012-01-01

    understanding of the processes by which genetic lesions perturb these networks and lead to disease phenotypes. Network biology will help circumvent fundamental obstacles in cancer treatment, such as drug resistance and metastasis, empowering personalized and tumor-specific cancer therapies.......Cells employ highly dynamic signaling networks to drive biological decision processes. Perturbations to these signaling networks may attract cells to new malignant signaling and phenotypic states, termed cancer network attractors, that result in cancer development. As different cancer cells reach...... these malignant states by accumulating different molecular alterations, uncovering these mechanisms represents a grand challenge in cancer biology. Addressing this challenge will require new systems-based strategies that capture the intrinsic properties of cancer signaling networks and provide deeper...

  14. MicroRNAs in Brain Metastases: Potential Role as Diagnostics and Therapeutics

    OpenAIRE

    Samer Alsidawi; Ehsan Malek; Driscoll, James J.

    2014-01-01

    Brain metastases remain a daunting adversary that negatively impact patient survival. Metastatic brain tumors affect up to 45% of all cancer patients with systemic cancer and account for ~20% of all cancer-related deaths. A complex network of non-coding RNA molecules, microRNAs (miRNAs), regulate tumor metastasis. The brain micro-environment modulates metastatic tumor growth; however, defining the precise genetic events that promote metastasis in the brain niche represents an important, unres...

  15. Expression profiles of pivotal microRNAs and targets in thyroid papillary carcinoma: an analysis of The Cancer Genome Atlas

    Directory of Open Access Journals (Sweden)

    Cong D

    2015-08-01

    Full Text Available Dan Cong,1 Mengzi He,2 Silin Chen,2 Xiaoli Liu,1 Xiaodong Liu,2 Hui Sun11Jilin Provincial Key Laboratory of Surgical Translational Medicine, Department of Thyroid and Parathyroid Surgery, People’s Republic of China–Japan Union Hospital, 2Key Laboratory of Radiobiology (Ministry of Health, School of Public Health, Jilin University, Changchun, Jilin, People’s Republic of ChinaAbstract: In the present study, we analyzed microRNA (miRNA and gene expression profiles using 499 papillary thyroid carcinoma (PTC samples and 58 normal thyroid tissues obtained from The Cancer Genome Atlas database. A pivotal regulatory network of 18 miRNA and 16 targets was identified. Upregulated miRNAs (miR-222, miR-221, miR-146b, miR-181a/b/d, miR-34a, and miR-424 and downregulated miRNAs (miR-9-1, miR-138, miR-363, miR-20b, miR-195, and miR-152 were identified. Among them, the upregulation of miR-424 and downregulation of miR-363, miR-195, and miR-152 were not previously identified. The genes CCNE2 (also known as cyclin E2, E2F1, RARA, CCND1 (cyclin D1, RUNX1, ITGA2, MET, CDKN1A (p21, and COL4A1 were overexpressed, and AXIN2, TRAF6, BCL2, RARB, HSP90B1, FGF7, and PDGFRA were downregulated. Among them, CCNE2, COL4A1, TRAF6, and HSP90B1 were newly identified. Based on receiver operating characteristic curves, several miRNAs (miR-222, miR-221, and miR-34a and genes (CCND1 and MET were ideal diagnostic indicators, with sensitivities and specificities greater than 90%. The combination of inversely expressed miRNAs and targets improved diagnostic accuracy. In a clinical feature analysis, several miRNAs (miR-34a, miR-424, miR-20b, and miR-152 and genes (CCNE2, COL4A1, TRAF6, and HSP90B1 were associated with aggressive clinical features, which have not previously been reported. Our study not only identified a pivotal miRNA regulatory network associated with PTC but also provided evidence that miRNAs and target genes can be used as biomarkers in PTC diagnosis and clinical

  16. Research advance in microRNAs and breast cancer.%MicroRNA与乳腺癌研究进展

    Institute of Scientific and Technical Information of China (English)

    卞国奉; 陈爱军

    2012-01-01

    MicroRNAs (miRNAs) are a major class of small endogenous RNA molecules that post-transcription-ally regulate gene expression. Several miRNAs have been proved to be related to human cancers, including breast cancer. The loss of several tumor suppressor miRNAs and the overexpression of certain oncogenic miRNAs have been observed in breast cancers. Here we describe the relationship of miRNA with the tumorigenesis and metastasis of breast cancer.%MicroRNAs (miRNAs)是一种内源性的小RNA分子,在基因的转录后能调节其表达.许多MicroRNAs被证实与各种肿瘤相关,包括乳腺癌.某些抑癌性MicroRNAs的缺失和致癌性MicroRNAs的过表达已经在许多乳腺癌中被发现.本文就MicroRNAs与乳腺癌发生发展之间的联系以及与一些乳腺癌相关的MicroRNA及其作用作一综述.

  17. MicroRNAs are involved in cervical cancer development, progression, clinical outcome and improvement treatment response (Review).

    Science.gov (United States)

    González-Quintana, Víctor; Palma-Berré, Lizbeth; Campos-Parra, Alma D; López-Urrutia, Eduardo; Peralta-Zaragoza, Oscar; Vazquez-Romo, Rafael; Pérez-Plasencia, Carlos

    2016-01-01

    Cervical cancer (CC) is the third most diagnosed cancer among females worldwide and the fourth cause of cancer-related mortality. Prophylactic HPV vaccines and traditional pap-smear screening are undoubtedly capable of decreasing the incidence and mortality of CC. However, a large number of females succumb to the disease each year due to late diagnosis and resistance to conventional treatments. Thus, it is necessary to identify new molecular markers to predict the clinical outcome and to design powerful treatments. MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression and are involved in the modulation of several cell pathways associated with progression from pre-malignant to invasive and metastatic disease, increasing tumor malignancy. The aim of this review was to summarize the recent data that describe the important role of miRNAS involved in CC in order to determine their potential as prognostic biomarkers and as therapy targets. Studies of >40 miRNAs with roles in cancer regulation were identified. We also identified 17 miRNAs associated with progression, 12 involved with clinical outcome and 7 that improved CC treatment response. The present review is expected to broaden understanding of the functional role and potential clinical uses of miRNAs in CC. PMID:26530778

  18. Stathmin1 plays oncogenic role and is a target of microRNA-223 in gastric cancer.

    Directory of Open Access Journals (Sweden)

    Wei Kang

    Full Text Available Stathmin1 (STMN1 is a candidate oncoprotein and prognosis marker in several kinds of cancers. This study was aimed to analyze its expression and biological functions in gastric cancer. The expression of STMN1 was evaluated by qRT-PCR, western blot and immunohistochemistry. The biological function of STMN1 was determined by MTT proliferation assays, monolayer colony formation and cell invasion assays using small interference RNA technique in gastric cancer cell lines. We also explored the regulation of STMN1 expression by microRNA-223. STMN1 was upregulated in gastric cancer cell lines and primary gastric adenocarcinomas. STMN1-positive tumors were more likely to be found in old age group and associated with p53 nuclear expression. In diffuse type gastric adenocarcinomas, STMN1 expression was correlated with age (p = 0.043, T stage (p = 0.004 and lymph node metastasis (p = 0.046. Expression of STMN1 in diffuse type gastric adenocarcinoma was associated with poor disease specific survival by univariate analysis (p = 0.01. STMN1 knockdown in AGS and MKN7 cell lines suppressed proliferation (p<0.001, reduced monolayer colony formation (p<0.001, inhibited cell invasion and migration ability (p<0.001 and induced G1 phase arrest. siSTMN1 could also suppress cell growth in vivo (p<0. 01. We finally confirmed that STMN1 is a putative downstream target of miR-223 in gastric cancer. Our findings supported an oncogenic role of STMN1 in gastric cancer. STMN1 might serve as a prognostic marker and a potential therapeutic target for gastric cancer.

  19. MicroRNA-154 inhibits growth and invasion of breast cancer cells through targeting E2F5

    Science.gov (United States)

    Xu, Hui; Fei, Dan; Zong, Shan; Fan, Zhimin

    2016-01-01

    Accumulating evidence suggested that microRNA-154 (miR-154) might play important roles in the development of various cancer types. However, the role of miR-154 in breast cancer progression remains largely unknown. Here, miR-154 expression level was measured via quantitative real-time RT-PCR (qRT-PCR) in 36 pairs of human breast cancer tissues and adjacent normal breast tissues and in a panel of human breast cancer cell lines. Cell proliferation, cycle, migration, and invasion were assessed by CCK8 assay, flow cytometer assay, wound healing assay and transwell invasion assay, respectively. Luciferase reporter assay and Western blot was used to verify E2F transcription factor 5 protein (E2F5) as a novel target gene of miR-154. Our results showed that miR-154 was frequently downregulated in breast cancer tissues and cell lines. Overexpression of miR-154 in MCF-7 cells significantly inhibited cell proliferation, migration, and invasion, and increased cell arrest at G0/G1 stage in vitro. E2F5 was identified as a target of miR-154, and its expression was inversely correlated with miR-154 expression in clinical breast cancer tissues. In addition, downregulation of E2F5 in MCF7 cells had similar effect on cell proliferation, cycle, migration and invasion by miR-154 induced. These findings indicate that miR-154 acts as a tumor suppressor by targeting E2F5, suggesting miR-154 as a potential therapeutic target for the treatment of breast cancer. PMID:27398145

  20. Mutator activity induced by microRNA-155 (miR-155) links inflammation and cancer

    OpenAIRE

    Tili, Esmerina; Michaille, Jean-Jacques; Wernicke, Dorothee; Alder, Hansjuerg; Costinean, Stefan; Volinia, Stefano; Croce, Carlo M.

    2011-01-01

    Infection-driven inflammation has been implicated in the pathogenesis of ~15–20% of human tumors. Expression of microRNA-155 (miR-155) is elevated during innate immune response and autoimmune disorders as well as in various malignancies. However, the molecular mechanisms providing miR-155 with its oncogenic properties remain unclear. We examined the effects of miR-155 overexpression and proinflammatory environment on the frequency of spontaneous hypoxanthine phosphoribosyltransferase (HPRT) m...

  1. MicroRNA regulation of cancer metabolism: role in tumour suppression

    Czech Academy of Sciences Publication Activity Database

    Tomasetti, M.; Santarelli, L.; Neužil, Jiří; Dong, L.

    2014-01-01

    Roč. 19, part a SI (2014), s. 29-38. ISSN 1567-7249 R&D Projects: GA ČR(CZ) GAP301/10/1937; GA MŠk(CZ) ED1.1.00/02.0109 Institutional support: RVO:86652036 Keywords : MicroRNA * Mitochondria * Tumour suppression Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.249, year: 2014

  2. Loss of microRNA-27b contributes to breast cancer stem cell generation by activating ENPP1.

    Science.gov (United States)

    Takahashi, Ryou-u; Miyazaki, Hiroaki; Takeshita, Fumitaka; Yamamoto, Yusuke; Minoura, Kaho; Ono, Makiko; Kodaira, Makoto; Tamura, Kenji; Mori, Masaki; Ochiya, Takahiro

    2015-01-01

    Cancer stem cells (CSCs) have been identified in various types of cancer; however, the mechanisms by which cells acquire CSC properties such as drug resistance and tumour seeding ability are not fully understood. Here, we identified microRNA-27b (miR-27b) as a key regulator for the generation of a side-population in breast cancer cells that showed CSC properties, and also found that the anti-type II diabetes (T2D) drug metformin reduced this side-population via miR-27b-mediated repression of ectonucleotide pyrophosphatase/phosphodiesterase family member 1 (ENPP1), which is involved in T2D development. ENPP1 induced the generation of the side-population via upregulation of the ABCG2 transporter. ENPP1 was also identified as a substrate of the 26S proteasome, the activity of which is downregulated in CSCs. Overall, these results demonstrate that a T2D-associated gene plays an important role in tumour development and that its expression is strictly controlled at the mRNA and protein levels. PMID:26065921

  3. MicroRNA-196b regulates the homeobox B7-vascular endothelial growth factor axis in cervical cancer.

    Directory of Open Access Journals (Sweden)

    Christine How

    Full Text Available The down-regulation of microRNA-196b (miR-196b has been reported, but its contribution to cervical cancer progression remains to be investigated. In this study, we first demonstrated that miR-196b down-regulation was significantly associated with worse disease-free survival (DFS for cervical cancer patients treated with combined chemo-radiation. Secondly, using a tri-modal approach for target identification, we determined that homeobox-B7 (HOXB7 was a bona fide target for miR-196b, and in turn, vascular endothelial growth factor (VEGF was a downstream transcript regulated by HOXB7. Reconstitution of miR-196b expression by transient transfection resulted in reduced cell growth, clonogenicity, migration and invasion in vitro, as well as reduced tumor angiogenesis and tumor cell proliferation in vivo. Concordantly, siRNA knockdown of HOXB7 or VEGF phenocopied the biological effects of miR-196b over-expression. Our findings have demonstrated that the miR-196b/HOXB7/VEGF pathway plays an important role in cervical cancer progression; hence targeting this pathway could be a promising therapeutic strategy for the future management of this disease.

  4. The microRNA miR-34a Inhibits Non-Small Cell Lung Cancer (NSCLC) Growth and the CD44hi Stem-Like NSCLC Cells

    OpenAIRE

    Shi, Yang; Liu, Can; Liu, Xin; Tang, Dean G.; Wang, Junchen

    2014-01-01

    Lung cancer is among the most lethal malignancies with a high metastasis and recurrence rate, which is probably due to the existence of lung cancer stem cells (CSCs). CSCs in many tumors including non-small cell lung cancer (NSCLC) have been identified using adhesion molecular CD44, either individually or in combination with other marker(s). MicroRNAs (miRNAs) regulate both normal stem cells and CSCs and dysregulation of miRNAs has been implicated in tumorigenesis. Recently, miR-34a was found...

  5. Brain metastatic cancer cells release microRNA-181c-containing extracellular vesicles capable of destructing blood–brain barrier

    OpenAIRE

    Tominaga, Naoomi; Kosaka, Nobuyoshi; Ono, Makiko; Katsuda, Takeshi; Yoshioka, Yusuke; Tamura, Kenji; Lötvall, Jan; Nakagama, Hitoshi; Ochiya, Takahiro

    2015-01-01

    Brain metastasis is an important cause of mortality in breast cancer patients. A key event during brain metastasis is the migration of cancer cells through blood–brain barrier (BBB). However, the molecular mechanism behind the passage through this natural barrier remains unclear. Here we show that cancer-derived extracellular vesicles (EVs), mediators of cell–cell communication via delivery of proteins and microRNAs (miRNAs), trigger the breakdown of BBB. Importantly, miR-181c promotes the de...

  6. Up-regulated microRNA-143 in cancer stem cells differentiation promotes prostate cancer cells metastasis by modulating FNDC3B expression

    International Nuclear Information System (INIS)

    Metastatic prostate cancer is a leading cause of cancer-related death in men. Cancer stem cells (CSCs) are involved in tumor progression and metastasis, including in prostate cancer. There is an obvious and urgent need for effective cancer stem cells specific therapies in metastatic prostate cancer. MicroRNAs (miRNAs) are an important class of pervasive genes that are involved in a variety of biological functions, especially in cancer. The goal of this study was to identify miRNAs involved in prostate cancer metastasis and cancer stem cells. A microarray and qRT-PCR were performed to investigate the miRNA expression profiles in PC-3 sphere cells and adherent cells. A transwell assay was used to evaluate the migration of PC-3 sphere cells and adherent cells. MiR-143 was silenced with antisense oligonucleotides in PC-3, PC-3-M and LNCaP cells. The role of miR-143 in prostate cancer metastasis was measured by wound-healing and transwell assays in vitro and bioluminescence imaging in vivo. Bioinformatics and luciferase report assays were used to identify the target of miR-143. The expression of miR-143 and the migration capability were reduced in PC-3 sphere cells and progressively increased during sphere re-adherent culture. Moreover, the down-regulation of miR-143 suppressed prostate cancer cells migration and invasion in vitro and systemically inhibited metastasis in vivo. Fibronectin type III domain containing 3B (FNDC3B), which regulates cell motility, was identified as a target of miR-143. The inhibition of miR-143 increased the expression of FNDC3B protein but not FNDC3B mRNA in vitro and vivo. These data demonstrate for the first time that miR-143 was up-regulated during the differentiation of prostate cancer stem cells and promoted prostate cancer metastasis by repressing FNDC3B expression. This sheds a new insight into the post-transcriptional regulation of cancer stem cells differentiation by miRNAs, a potential approach for the treatment of prostate cancer

  7. Network of Cancer Genes (NCG 3.0): integration and analysis of genetic and network properties of cancer genes

    OpenAIRE

    D'Antonio, Matteo; Pendino, Vera; Sinha, Shruti; Ciccarelli, Francesca D.

    2011-01-01

    The identification of a constantly increasing number of genes whose mutations are causally implicated in tumor initiation and progression (cancer genes) requires the development of tools to store and analyze them. The Network of Cancer Genes (NCG 3.0) collects information on 1494 cancer genes that have been found mutated in 16 different cancer types. These genes were collected from the Cancer Gene Census as well as from 18 whole exome and 11 whole-genome screenings of cancer samples. For each...

  8. Diagnostic value of circulating microRNAs for nasopharyngeal cancer: A systematic review and meta-analysis

    Directory of Open Access Journals (Sweden)

    Zhiyi Wang

    2014-01-01

    Full Text Available Aim: Circulating microRNAs (miRNA are a promising diagnostic tool for lung and gastric cancer. However, their diagnostic value in nasopharyngeal cancer remains unknown. Thus, this study aims to systematically evaluate the diagnostic accuracy of circulating miRNA for nasopharyngeal cancer. Method: Eligible studies were searched and selected from the PubMed, EMBASE, and Cochrane CENTRAL databases. Results from these included studies were pooled using random-effects models. Sensitivity, specificity, positive likelihood ratio (PLR, negative likelihood ratio (NLR, and diagnostic odds ratio (DOR were calculated to assess the overall performance of miRNA-based assay. Summary receiver operating characteristic (SROC curves were plotted to evaluate the overall diagnostic accuracy of circulating miRNA detection. Results: Seven publications were considered eligible for this systematic review, and four studies were finally chosen for this meta-analysis. In the diagnostic meta-analysis, the overall pooled results for sensitivity, specificity, PLR, NLR, and DOR were 0.87 (95% confidence interval [CI]: 0.83-0.90, 0.87 (95% CI: 0.82-0.91, 7.529 (95% CI, 2.575-22.013, 0.145 (95% CI, 0.058-0.363, and 64.045 (95% CI, 10.176-403.10, respectively. The area under SROC curve was 0.95. Conclusion: Circulating miRNA detection presents an enormous potential in diagnosing nasopharyngeal cancer. Studies with a large sample size of nasopharyngeal cancer patients must be conducted to verify the diagnostic value of circulating miRNA.

  9. Serum microRNA-21 as a potential diagnostic biomarker for breast cancer: a systematic review and meta-analysis.

    Science.gov (United States)

    Li, Shichao; Yang, Xiaorong; Yang, Jinmei; Zhen, Jiesheng; Zhang, Dechun

    2016-02-01

    Serum microRNA-21 (miR-21) expression has been shown to be significantly up-regulated in breast cancer, which implies that it could be a biomarker to discriminate breast cancer patients from healthy controls. We therefore performed this meta-analysis to assess the diagnostic value of miR-21 for breast cancer. Relevant articles were collected from PubMed, Scopus, Embase, the Cochrane Library, BioMed Central, ISI Web of Knowledge, China National Knowledge Infrastructure, Wan Fang Data and Technology of Chongqing databases, from inception to June 10, 2014 by two independent researchers. Diagnostic capacity of miR-21 for breast cancer was assessed using pooled sensitivity and specificity, diagnostic odds ratio (DOR), area under the summary receiver operating characteristic (AUC) and Fagan's nomogram. Meta-Disc software and Stata SE 12.0 were used to investigate the source of heterogeneity and to perform the meta-analysis. We used six studies with a total of 438 patients and 228 healthy controls in this meta-analysis. The pooled sensitivity, specificity and DOR were 0.79 [95 % confidence interval (CI) 0.66-0.87], 0.85 (95 % CI 0.75-0.91) and 19.46 (95 % CI 8.74-43.30), respectively; positive and negative likelihood ratios were 5 and 0.25, and AUC was 0.89 (95 % CI 0.86-0.91). In addition, heterogeneity was clearly apparent but was not caused by the threshold effect. This meta-analysis suggests that miR-21 is a potential biomarker for early diagnosis of breast cancer with high sensitivity and specificity, and its clinical application warrants further investigation. PMID:25516467

  10. Genomics, microRNA, epigenetics, and proteomics for future diagnosis, treatment and monitoring response in upper GI cancers.

    Science.gov (United States)

    Brücher, Björn L D M; Li, Yan; Schnabel, Philipp; Daumer, Martin; Wallace, Timothy J; Kube, Rainer; Zilberstein, Bruno; Steele, Scott; Voskuil, Jan L A; Jamall, Ijaz S

    2016-12-01

    One major objective for our evolving understanding in the treatment of cancers will be to address how a combination of diagnosis and treatment strategies can be used to integrate patient and tumor variables with an outcome-oriented approach. Such an approach, in a multimodal therapy setting, could identify those patients (1) who should undergo a defined treatment (personalized therapy) (2) in whom modifications of the multimodal therapy due to observed responses might lead to an improvement of the response and/or prognosis (individualized therapy), (3) who might not benefit from a particular toxic treatment regimen, and (4) who could be identified early on and thereby be spared the morbidity associated with such treatments. These strategies could lead in the direction of precision medicine and there is hope of integrating translational molecular data to improve cancer classifications. In order to achieve these goals, it is necessary to understand the key issues in different aspects of biotechnology to anticipate future directions of personalized and individualized diagnosis and multimodal treatment strategies. Providing an overview of translational data in cancers proved to be a challenge as different methods and techniques used to obtain molecular data are used and studies are based on different tumor entities with different tumor biology and prognoses as well as vastly different therapeutic approaches. The pros and cons of the available methodologies and the potential response data in genomics, microRNA, epigenetics and proteomics with a focus on upper gastrointestinal cancers are considered herein to allow for an understanding of where these technologies stand with respect to cancer diagnosis, prognosis and treatment. PMID:27053248

  11. Network Modeling Identifies Molecular Functions Targeted by miR-204 to Suppress Head and Neck Tumor Metastasis

    OpenAIRE

    Lee, Younghee; Yang, Xinan; Huang, Yong; FAN, HANLI; Zhang, Qingbei; Wu, Youngfei; Li, Jianrong; Hasina, Rifat; Cheng, Chao; Lingen, Mark W.; Gerstein, Mark B.; Weichselbaum, Ralph R.; Xing, H. Rosie; Lussier, Yves A.

    2010-01-01

    Due to the large number of putative microRNA gene targets predicted by sequence-alignment databases and the relative low accuracy of such predictions which are conducted independently of biological context by design, systematic experimental identification and validation of every functional microRNA target is currently challenging. Consequently, biological studies have yet to identify, on a genome scale, key regulatory networks perturbed by altered microRNA functions in the context of cancer. ...

  12. Prognostic significance of microRNA gene polymorphisms in patients with surgically resected colorectal cancer

    OpenAIRE

    Jang, Moon Ju; Kim, Jong Woo; MIN, KYUNG TAE; Jeon, Young Joo; Oh, Doyeun; KIM, NAM KEUN

    2011-01-01

    MicroRNAs (miRNAs) are small 19- to 22-nucleotide sequences of RNA that participate in the regulation of cell differentiation, cell cycle progression and apoptosis. Although single-nucleotide polymorphisms (SNPs) in miRNA regions are considered unlikely to be functionally important, nucleotide variations within the sequences of primary (pri)- or precursor (pre)-miRNAs may affect miRNA processing and ultimately result in the modification of miRNA expression. The aim of this study was to invest...

  13. An elegant miRror: microRNAs in stem cells, developmental timing and cancer

    OpenAIRE

    Nimmo, Rachael A.; Slack, Frank J.

    2009-01-01

    MicroRNAs (miRNAs) were first discovered in genetic screens for regulators of developmental timing in the stem-cell-like seam cell lineage in Caenorhabditis elegans. As members of the heterochronic pathway, the lin-4 and let-7 miRNAs are required in the seam cells for the correct progression of stage-specific events and to ensure that cell cycle exit and terminal differentiation occur at the correct time. Other heterochronic genes such as lin-28 and lin-41 are direct targets of the lin-4 and ...

  14. The Application of MicroRNA in The Diagnosis and Prognosis of Gastric Cancer%研究循环microRNA在胃癌诊断和预后预测中的应用分析

    Institute of Scientific and Technical Information of China (English)

    李佳鑫

    2015-01-01

    In recent years, the study found that the presence of a class of gastric cancer tissue can affect the development of cancer microRNA, that is, RNA. MicroRNA as a marker for diagnosis of gastric cancer, can effectively maintain the stability of cancer cells. In this study, the microRNA and the prognosis of gastric cancer in the plasma were predicted and the results were summarized.%近几年,研究发现在胃癌组织中存在一类能够影响癌症发展的RNA,即microRNA。microRNA作为诊断胃癌的标记物,能够有效的维持癌细胞稳定性。本次研究就血浆之中存在的microRNA同胃癌的诊断与预后方面进行预测并展开综述。

  15. Genome-Wide CRISPR-Cas9 Screen Identifies MicroRNAs That Regulate Myeloid Leukemia Cell Growth

    Science.gov (United States)

    Wallace, Jared; Hu, Ruozhen; Mosbruger, Timothy L.; Dahlem, Timothy J.; Stephens, W. Zac; Rao, Dinesh S.; Round, June L.; O’Connell, Ryan M.

    2016-01-01

    Mammalian microRNA expression is dysregulated in human cancer. However, the functional relevance of many microRNAs in the context of tumor biology remains unclear. Using CRISPR-Cas9 technology, we performed a global loss-of-function screen to simultaneously test the functions of individual microRNAs and protein-coding genes during the growth of a myeloid leukemia cell line. This approach identified evolutionarily conserved human microRNAs that suppress or promote cell growth, revealing that microRNAs are extensively integrated into the molecular networks that control tumor cell physiology. miR-155 was identified as a top microRNA candidate promoting cellular fitness, which we confirmed with two distinct miR-155-targeting CRISPR-Cas9 lentiviral constructs. Further, we performed anti-correlation functional profiling to predict relevant microRNA-tumor suppressor gene or microRNA-oncogene interactions in these cells. This analysis identified miR-150 targeting of p53, a connection that was experimentally validated. Taken together, our study describes a powerful genetic approach by which the function of individual microRNAs can be assessed on a global level, and its use will rapidly advance our understanding of how microRNAs contribute to human disease. PMID:27081855

  16. A Complex Network of MicroRNAs Expressed in Brain and Genes Associated with Amyotrophic Lateral Sclerosis

    Directory of Open Access Journals (Sweden)

    Santosh Shinde

    2013-01-01

    Full Text Available Amyotrophic Lateral Sclerosis (ALS is a rare neurological disease affecting mainly motor neurons and often leads to paralysis and death in extreme cases. For exploring the role of microRNAs in genes regulation in ALS disease, miRanda was employed for prediction of target sites of miRNAs expressed in various parts of brain and CNS on 35 genes associated with ALS. Similar search was conducted using TargetScan and PicTar for prediction of target sites in 3′ UTR only. 1456 target sites were predicted using miRanda and more target sites were found in 5′ UTR and CDS region as compared to 3′ UTR. 11 target sites were predicted to be common by all the algorithms and, thus, these represent the most significant sites. Target site hotspots were identified and were recognized as hotspots for multiple miRNAs action, thus, acting as favoured sites of action for the repression of gene expression. The complex interplay of genes and miRNAs brought about by multiplicity and cooperativity was explored. This investigation will aid in elucidating the mechanism of action of miRNAs for the considered genes. The intrinsic network of miRNAs expressed in nervous system and genes associated with ALS may provide rapid and effective outcome for therapeutic applications and diagnosis.

  17. MicroRNA 135a suppresses lymph node metastasis through down-regulation of ROCK1 in early gastric cancer.

    Directory of Open Access Journals (Sweden)

    Ji-Young Shin

    Full Text Available MicroRNAs (miRNAs play a critical role in gastric cancer progression and metastasis. This study investigated the role of miRNA-135a in early gastric cancer (EGC including lymph node (LN metastasis. We examined the correlation between miRNA-135a expression and clinical outcomes in 59 patients who underwent surgery for EGC. Using gastric cancer cell lines, we performed functional and target gene analyses. miRNA-135a expression was down-regulated in 33.9% of patients. These patients showed a significantly more advanced stage (TNM stage ≥ IB, 35.0% vs. 12.8%, p = 0.045 and higher rate of LN metastasis (30.0% vs. 5.1%, p = 0.014 than those with up-regulation of miRNA-135a expression. In a multivariate analysis, down-regulation of miRNA-135a was an independent risk factor for LN metastasis (adjusted odds ratio, 8.04; 95% confidence interval, 1.08-59.81; p = 0.042. Functional analyses using gastric cancer cell lines showed that miRNA-135a suppressed cell viability, epithelial-mesenchymal transition, cell invasion, and migration. ROCK1 was a target of miRNA-135a and its expression was inversely correlated to that of miRNA-135a. ROCK1 expression was significantly increased in EGC patients with LN metastasis than in those without LN metastasis. Our results confirm the tumor-suppressive role of miRNA-135a, and demonstrate its role in LN metastasis in EGC. miRNA-135a and its target gene ROCK1 may be novel therapeutic and prognostic targets for EGC.

  18. Nanovesicle-mediated systemic delivery of microRNA-34a for CD44 overexpressing gastric cancer stem cell therapy.

    Science.gov (United States)

    Jang, Eunji; Kim, Eunjung; Son, Hye-Young; Lim, Eun-Kyung; Lee, Hwunjae; Choi, Yuna; Park, Kwangyeol; Han, Seungmin; Suh, Jin-Suck; Huh, Yong-Min; Haam, Seungjoo

    2016-10-01

    The cancer stem cell (CSC) hypothesis postulates that cancer cells overexpressing CD44 are marked as CSCs that cause tumorigenesis and recurrence. This hypothesis suggests that CD44 is a potential therapeutic target that can interfere with CSCs qualities. MicroRNA-34a (miR-34a) is a promising candidate for CD44 repression-based cancer therapy as it has been reported to inhibit proliferation, metastasis, and survival of CD44-positive CSCs. Here, we used nanovesicles containing PLI/miR complexes (NVs/miR) to systemically deliver miR-34a and induce miR-34a-triggered CD44 suppression in orthotopically and subcutaneously implanted tumors in nude mice. Poly(l-lysine-graft-imidazole) (PLI) condenses miRs and is functionally modified to deliver miRs to the site of action by buffering effect of imidazole residues under endosomal pH. Indeed, NVs/miR consisting of PEGylated lipids enveloping PLI/miR complexes greatly reduced inevitable toxicity of polycations by compensating their surface charge and markedly improved their in vivo stability and accumulation to tumor tissue compared to PLI/miR polyplexes. Our NVs-mediated miR-34a delivery system specifically increased endogenous target miR levels, thereby attenuating proliferation and migration of gastric cancer cells by repressing the expression of CD44 with decreased levels of Bcl-2, Oct 3/4 and Nanog genes. Our strategy led to a greater therapeutic outcome than PLI-based delivery with highly selective tumor cell death and significantly delayed tumor growth in CD44-positive tumor-bearing mouse models, thus providing a fundamental therapeutic window for CSCs. PMID:27497057

  19. Induction of cancer-related microRNA expression profiling using excretory-secretory products of Clonorchis sinensis.

    Science.gov (United States)

    Pak, Jhang Ho; Kim, In Ki; Kim, Seon Min; Maeng, Sejung; Song, Kyoung Ju; Na, Byoung-Kuk; Kim, Tong-Soo

    2014-12-01

    Clonorchis sinensis is a carcinogenic human liver fluke by which chronic infection is strongly associated with the development of cholangiocarcinoma. Although this cholangiocarcinoma is caused by both physical and chemical irritation from direct contact with adult worms and their excretory-secretory products (ESPs), the precise molecular events of the host-pathogen interactions remain to be elucidated. To better understand the effect of C. sinensis infection on cholangiocarcinogenesis, we profiled the kinetics of changes in cancer-related microRNAs (miRNAs) in human cholangiocarcinoma cells (HuCCT1) treated with C. sinensis ESPs for different periods. Using miRNA microarray chips containing 135 cancer-related miRNAs, we identified 16 miRNAs showing differentially altered expression following ESP exposure. Of these miRNAs, 13 were upregulated and 3 were downregulated in a time-dependent manner compared with untreated controls. Functional clustering of these dysregulated miRNAs revealed involvement in cell proliferation, inflammation, oncogene activation/suppression, migration/invasion/metastasis, and DNA methylation. In particular, decreased expression of let-7i, a tumor suppressor miRNA, was found to be associated with the ESP-induced upregulation of TLR4 mRNA and protein, which contribute to host immune responses against liver fluke infection. Further real-time quantitative PCR analysis using ESP-treated normal cholangiocytes (H69) revealed that the expressions of nine miRNAs (miR-16-2, miR-93, miR-95, miR-153, miR-195, miR-199-3P, let7a, let7i, and miR-124a) were similarly regulated, indicating that the cell proliferation and inhibition of tumor suppression mediated by these miRNAs is common to both cancerous and non-cancerous cells. These findings constitute further our understanding of the multiple cholangiocarcinogenic pathways triggered by liver fluke infection. PMID:25217977

  20. Direct regulation of LAMP1 by tumor-suppressive microRNA-320a in prostate cancer

    Science.gov (United States)

    OKATO, ATSUSHI; GOTO, YUSUKE; KUROZUMI, AKIRA; KATO, MAYUKO; KOJIMA, SATOKO; MATSUSHITA, RYOSUKE; YONEMORI, MASAYA; MIYAMOTO, KAZUTAKA; ICHIKAWA, TOMOHIKO; SEKI, NAOHIKO

    2016-01-01

    Advanced prostate cancer (PCa) metastasizes to bone and lymph nodes, and currently available treatments cannot prevent the progression and metastasis of the disease. Therefore, an improved understanding of the molecular mechanisms of the progression and metastasis of advanced PCa using current genomic approaches is needed. Our miRNA expression signature in castration-resistant prostate cancer (CRPC) revealed that microRNA-320a (miR-320a) was significantly reduced in cancer tissues, suggesting that miR-320a may be a promising anticancer miRNA. The aim of this study was to investigate the functional roles of miR-320a in naïve PCa and CRPC cells and to identify miR-320a-regulated genes involved in PCa metastasis. The expression levels of miR-320a were significantly reduced in naïve PCa, CRPC specimens, and PCa cell lines. Restoration of mature miR-320a in PCa cell lines showed that miR-320a significantly inhibited cancer cell migration and invasion. Moreover, we found that lysosomal-associated membrane protein 1 (LAMP1) was a direct target of miR-320a in PCa cells. Silencing of LAMP1 using siRNA significantly inhibited cell proliferation, migration, and invasion in PCa cells. Overexpression of LAMP1 was observed in PCa and CRPC clinical specimens. Moreover, downstream pathways were identified using si-LAMP1-transfected cells. The discovery of tumor-suppressive miR-320a-mediated pathways may provide important insights into the potential mechanisms of PCa metastasis. PMID:27212625

  1. Implications of MicroRNAs in the Treatment of Gefitinib-Resistant Non-Small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Thomas K. Sin

    2016-02-01

    Full Text Available Non-small cell lung cancer (NSCLC represents about 85% of the reported cases of lung cancer. Acquired resistance to targeted therapy with epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs, such as gefitinib, is not uncommon. It is thus vital to explore novel strategies to restore sensitivity to gefitinib. Provided that microRNAs (miRNAs negatively regulate their gene targets at the transcriptional level, it is speculated that miRNA mimetics may reduce the expression, activity and signal transduction of EGFR so that sensitization of tumour sites to gefitinib-induced cytotoxicity can be achieved. Indeed, a growing body of evidence has shown that the manipulation of endogenous levels of miRNA not only attenuates the EGFR/PI3K/Akt phosphorylation cascade, but also restores apoptotic cell death in in vitro models of experimentally-induced gefitinib resistance and provoked tumour regression/shrinkage in xenograft models. These data are in concordant with the clinical data showing that the differential expression profiles of miRNA in tumour tissues and blood associate strongly with drug response and overall survival. Furthermore, another line of studies indicate that the chemopreventive effects of a variety of natural compounds may involve miRNAs. The present review aims to discuss the therapeutic capacity of miRNAs in relation to recent discoveries on EGFR-TKI resistance, including chronic drug exposure and mutations.

  2. Increased Circulating MicroRNA-155 as a Potential Biomarker for Breast Cancer Screening: A Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Faliang Wang

    2014-05-01

    Full Text Available The objective of this meta-analysis was to determine the diagnostic accuracy of circulating microRNA-155 (miR-155 for breast cancer (BC. PubMed, Embase, EBSCO (ASP/BSP, Cochrane Library and China National Knowledge Infrastructure (CNKI were searched up to 30 January 2014 for eligible studies. Quality Assessment of Diagnostic Accuracy Studies (QUADAS was employed to assess the quality of the included studies. Meta-analysis were performed in Meta-Disc 1.4 and Stata 12.0. Three studies with total 184 BC patients and 75 control individuals were included in this meta-analysis. All of the included studies are of high quality (QUADAS scores 12 or 13. The summary estimates revealed that the pooled sensitivity is 79% (95% confidence interval (CI: 72%–84% and the specificity is 85% (95% CI: 75%–92%, for the diagnosis of breast cancer. In addition, the area under the summary ROC curve (AUC is 0.9217. The current evidence suggests that circulating miR-155 has the potential diagnostic value with a high sensitivity and specificity for BC. More prospective studies on the diagnostic value of circulating miR-155 for BC are needed in the future.

  3. Decreased expression of microRNA let-7i and its association with chemotherapeutic response in human gastric cancer

    Directory of Open Access Journals (Sweden)

    Liu Kun

    2012-10-01

    Full Text Available Abstract Background MicroRNA let-7i has been proven to be down-regulated in many human malignancies and correlated with tumor progression and anticancer drug resistance. Our study aims to characterize the contribution of miRNA let-7i to the initiation and malignant progression of locally advanced gastric cancer (LAGC, and evaluate its possible value in neoadjuvant chemotherapeutic efficacy prediction. Methods Eighty-six previously untreated LAGC patients who underwent preoperative chemotherapy and radical resection were included in our study. Let-7i expression was examined for pairs of cancer tissues and corresponding normal adjacent tissues (NATs, using quantitative RT-PCR. The relationship of let-7i level to clinicopathological characteristics, pathologic tumor regression grades after chemotherapy, and overall survival (OS was also investigated. Results Let-7i was significantly down-regulated in most tumor tissues (78/86: 91% compared with paired NATs (P P =0.024 independently of other clinicopathological factors, including tumor node metastasis (TNM stage (HR = 3.226, P = 0.013, depth of infiltration (HR = 4.167, P P = 0.037. Conclusions These findings indicate that let-7i may be a good candidate for use a therapeutic target and a potential tissue marker for the prediction of chemotherapeutic sensitivity and prognosis in LAGC patients.

  4. Serum level of microRNA-147 as diagnostic biomarker in human non-small cell lung cancer.

    Science.gov (United States)

    Chu, Guangmin; Zhang, Jianbo; Chen, Xiaobing

    2016-08-01

    Objectives In this study, we intended to examine the gene expression level and the clinical significance of microRNA-147 (miR-147) in cancer tissues and sera of patients with non-small cell lung cancer (NSCLC). Methods Quantitative real-time PCR (qRT-PCR) was used to investigate the expression levels of miR-147 in 32 paired NSCLC tissues and their adjacent normal lung tissues, sera of 122 control and 87 NSCLC patients. The correlation of serum miR-147 expression level with clinicopathological characteristics, and the prognosis of NSCLC patients was statistically evaluated. Results MiR-147 was significantly down-regulated in NSCLC tissues than in paired adjacent normal tissues, and in sera of NSCLC patients than in sera of control patients. In addition, serum miR-147 was markedly down-regulated in advanced NSCLC patients and the patients with lymph node metastasis (LNM). Low serum miR-147 expression level was found to be significantly correlated with tumor, lymph node, metastasis stage, LNM, and tumor size. Statistical analysis showed that patients with low serum miR-147 had much worse overall survival, and low serum miR-147 expression level was an independent prognostic factor for poor prognosis for NSCLC. Conclusion Low serum miR-147 expression level may be a useful biomarker for patients with NSCLC. PMID:26581116

  5. MicroRNA-375 targets Hippo-signaling effector YAP in liver cancer and inhibits tumor properties

    International Nuclear Information System (INIS)

    Hepatocellular carcinoma (HCC) is a malignant form of liver cancer that ranks the second leading cause of cancer-related deaths in China and many Asia regions. The dismal outcome reflects the need for a better understanding of the transcriptional control of oncogenic signaling pathway. Our recent findings have identified yes-associated protein (YAP) is a potent oncogenic driver and independent prognostic risk factor of HCC. The present study aims to elucidate the transcriptional regulation of YAP targeted by microRNA (miRNA). miR-375 is a putative target and was found significantly down-regulated in the tumor versus adjacent non-tumor tissues of HCC patients (n = 48). As determined by luciferase reporter assay, we found ectopic expression of miR-375 could diminish the transcriptional activity of YAP. Furthermore, immunoblotting revealed miR-375 suppressed endogenous YAP protein level. Functional assays showed that miR-375 was able to inhibit proliferation and invasion of HCC cells. Conclusion: miR-375 is an important regulator of YAP oncogene, implicating a potential therapeutic role in HCC treatment.

  6. MicroRNA-155 is required for effector CD8+ T cell responses to virus infection and cancer

    Science.gov (United States)

    DUDDA, Jan C.; SALAUN, Bruno; JI, Yun; PALMER, Douglas C.; Monnot, Gwennaelle C.; MERCK, Estelle; BOUDOUSQUIE, Caroline; UTZSCHNEIDER, Daniel T.; ESCOBAR, Thelma M.; PERRET, Rachel; MULJO, Stefan A.; HEBEISEN, Michael; RUFER, Nathalie; ZEHN, Dietmar; DONDA, Alena; RESTIFO, Nicholas P.; HELD, Werner; GATTINONI, Luca; ROMERO, Pedro

    2013-01-01

    SUMMARY MicroRNAs regulate the function of several immune cells but their role in promoting CD8+ T-cell immunity remains unknown. Here we report that miR-155 is required for CD8+ T-cell responses to both virus and cancer. In the absence of miR-155, accumulation of effector CD8+ T cells was severely reduced during acute and chronic viral infections and control of virus replication was impaired. Similarly, Mir155-/- CD8+ T cells were in effective at controlling tumor growth, whereas miR-155 overexpression enhanced the antitumor response. miR-155 deficiency resulted in accumulation of SOCS-1 causing defective cytokine signaling through STAT5. Consistently, enforced expression of SOCS-1 in CD8+ T cells phenocopied the miR-155 deficiency, whereas SOCS-1 silencing augmented tumor destruction. These findings identify miR-155 and its target SOCS-1 as key regulators of effector CD8+ T cells that can be modulated to potentiate immunotherapies for infectious diseases and cancer. PMID:23601686

  7. Metformin inhibits cell growth by upregulating microRNA-26a in renal cancer cells

    OpenAIRE

    Yang, Feng-Qiang; Wang, Ji-Jiao; Yan, Jia-Sheng; Huang, Jian-Hua; Li, Wei; Che, Jian-Ping; Wang, Guang-Chun; Liu, Min; Zheng, Jun-Hua

    2014-01-01

    Accumulating evidence suggests that metformin, a biguanide class of anti-diabetic drugs, possesses anti-cancer properties and may reduce cancer risk and improve prognosis. However, the mechanism by which metformin affects various cancers, including renal cancer still unknown. MiR-26a induces cell growth, cell cycle and cell apoptosis progression via direct targeting of Bcl-2, clyclin D1 and PTEN in cancer cells. In the present study, we used 786-O human renal cancer cell lines to study the ef...

  8. Online Social Networks - Opportunities for Empowering Cancer Patients.

    Science.gov (United States)

    Mohammadzadeh, Zeinab; Davoodi, Somayeh; Ghazisaeidi, Marjan

    2016-01-01

    Online social network technologies have become important to health and apply in most health care areas. Particularly in cancer care, because it is a disease which involves many social aspects, online social networks can be very useful. Use of online social networks provides a suitable platform for cancer patients and families to present and share information about their medical conditions, address their educational needs, support decision making, and help to coping with their disease and improve their own outcomes. Like any other new technologies, online social networks, along with many benefits, have some negative effects such as violation of privacy and publication of incorrect information. However, if these effects are managed properly, they can empower patients to manage cancer through changing behavioral patterns and enhancing the quality of cancer patients lives This paper explains some application of online social networks in the cancer patient care process. It also covers advantages and disadvantages of related technologies. PMID:27039815

  9. Network analysis of microRNAs, genes and their regulation in mantle cell lymphoma.

    Science.gov (United States)

    Deng, Si-Yu; Guo, Xiao-Xin; Wang, Ning; Wang, Kun-Hao; Wang, Shang

    2015-01-01

    The pathogenesis of mantle cell lymphoma, a special subtype of lymphoma that is invasive and indolent and has a median survival of 3 to 4 years, is still partially unexplained. Much research about genes and miRNAs has been conducted in recent years, but interactions and regulatory relations of genetic elements which may play a vital role in genesis of MCL have attracted only limited attention. The present study concentrated on regulatory relations about genes and miRNAs contributing to MCL pathogenesis. Numerous experimentally validated raw data were organized into three topology networks, comprising differentially expressed, associated and global examples. Comparison of similarities and dissimilarities of the three regulating networks, paired with the analysis of the interactions between pairs of elements in every network, revealed that the differentially expressed network illuminated the carcinogenicity mechanism of MCL and the related network further described the regulatory relations involved, including prevention, diagnosis, development and therapy. Three kinds of regulatory relations for host genes including miRNAs, miRNAs targeting genes and genes regulating miRNAs were concluded macroscopically. Regulation of the differentially expressed miRNAs was also analyzed, in terms of abnormal gene expression affecting the MCL pathogenesis. Special regulatory relations were uncovered. For example, auto-regulatory loops were found in the three topology networks, key pathways of the nodes being highlighted. The present study focused on a novel point of view revealing important influencing factors for MCL pathogenesis. PMID:25684471

  10. Suppression of Cancer Stemness p21-regulating mRNA and microRNA Signatures in Recurrent Ovarian Cancer Patient Samples

    LENUS (Irish Health Repository)

    Gallagher, Michael F

    2012-01-19

    Abstract Background Malignant ovarian disease is characterised by high rates of mortality due to high rates of recurrent chemoresistant disease. Anecdotal evidence indicates this may be due to chemoresistant properties of cancer stem cells (CSCs). However, our understanding of the role of CSCs in recurrent ovarian disease remains sparse. In this study we used gene microarrays and meta-analysis of our previously published microRNA (miRNA) data to assess the involvement of cancer stemness signatures in recurrent ovarian disease. Methods Microarray analysis was used to characterise early regulation events in an embryonal carcinoma (EC) model of cancer stemness. This was then compared to our previously published microarray data from a study of primary versus recurrent ovarian disease. In parallel, meta-analysis was used to identify cancer stemness miRNA signatures in tumor patient samples. Results Microarray analysis demonstrated a 90% difference between gene expression events involved in early regulation of differentiation in murine EC (mEC) and embryonic stem (mES) cells. This contrasts the known parallels between mEC and mES cells in the undifferentiated and well-differentiated states. Genelist comparisons identified a cancer stemness signature set of genes in primary versus recurrent data, a subset of which are known p53-p21 regulators. This signature is present in primary and recurrent or in primary alone but essentially never in recurrent tumors specifically. Meta-analysis of miRNA expression showed a much stronger cancer stemness signature within tumor samples. This miRNA signature again related to p53-p21 regulation and was expressed prominently in recurrent tumors. Our data indicate that the regulation of p53-p21 in ovarian cancer involves, at least partially, a cancer stemness component. Conclusion We present a p53-p21 cancer stemness signature model for ovarian cancer. We propose that this may, at least partially, differentially regulate the p53-p21

  11. Suppression of cancer stemness p21-regulating mRNA and microRNA signatures in recurrent ovarian cancer patient samples

    Directory of Open Access Journals (Sweden)

    Gallagher Michael F

    2012-01-01

    Full Text Available Abstract Background Malignant ovarian disease is characterised by high rates of mortality due to high rates of recurrent chemoresistant disease. Anecdotal evidence indicates this may be due to chemoresistant properties of cancer stem cells (CSCs. However, our understanding of the role of CSCs in recurrent ovarian disease remains sparse. In this study we used gene microarrays and meta-analysis of our previously published microRNA (miRNA data to assess the involvement of cancer stemness signatures in recurrent ovarian disease. Methods Microarray analysis was used to characterise early regulation events in an embryonal carcinoma (EC model of cancer stemness. This was then compared to our previously published microarray data from a study of primary versus recurrent ovarian disease. In parallel, meta-analysis was used to identify cancer stemness miRNA signatures in tumor patient samples. Results Microarray analysis demonstrated a 90% difference between gene expression events involved in early regulation of differentiation in murine EC (mEC and embryonic stem (mES cells. This contrasts the known parallels between mEC and mES cells in the undifferentiated and well-differentiated states. Genelist comparisons identified a cancer stemness signature set of genes in primary versus recurrent data, a subset of which are known p53-p21 regulators. This signature is present in primary and recurrent or in primary alone but essentially never in recurrent tumors specifically. Meta-analysis of miRNA expression showed a much stronger cancer stemness signature within tumor samples. This miRNA signature again related to p53-p21 regulation and was expressed prominently in recurrent tumors. Our data indicate that the regulation of p53-p21 in ovarian cancer involves, at least partially, a cancer stemness component. Conclusion We present a p53-p21 cancer stemness signature model for ovarian cancer. We propose that this may, at least partially, differentially regulate the p

  12. Potential role of microRNA-21 in the diagnosis of gastric cancer: a meta-analysis.

    Directory of Open Access Journals (Sweden)

    Zongyue Zeng

    Full Text Available INTRODUCTION: Accumulating evidences indicate that microRNA-21(miR-21 show significant high concentration in plasma of gastric cancer (GC patients compared to normal individuals, suggesting that it may be a useful novel diagnostic biomarker for gastric cancer. Therefore, we aimed to assess the potential diagnostic value of miR-21 for gastric cancer in this study. METHODS: Literature database including PubMed, Embase, the Cochrane Library, Web of Science, Ovid, SciVerse, Science Direct, Scopus, BioMed Central, Biosis previews,Chinese Biomedical Literature Database (CBM, Chinese National Knowledge Infrastructure (CNKI, Technology of Chongqing (VIP, and Wan Fang DATA were searched for publications concerning the diagnostic value of miR-21 for GC without language restriction. The quality of each study was scored with the Quality Assessment of Diagnostic Accuracy Studies (QUADAS. Then, data were retrieved from any qualified article hits and subject to meta-analysis. Receiver operating characteristic curves (ROC were used to check the overall test performance. Evidence of heterogeneity was evaluated using the Chi-square and I (2 test. RESULTS: Five studies with a total 251 GC patients and 184 control individuals were included in this meta-analysis. All of the included studies are of high quality (QUADAS score$13. The summary estimates revealed that the pooled sensitivity is 66.5% (95% confidence interval (CI: 55.0%-76.3% and the specificity is 83.1% (95% CI: 69.4%-91.5%. In addition, the area under the summary ROC curve (AUC is 0.80. CONCLUSION: The current evidence suggests that miR-21 has potential diagnostic value with a moderate sensitivity and specificity for GC. More prospective studies on the diagnostic value of miR-21 for GC are needed in the future.

  13. MicroRNA-490-3p inhibits proliferation of A549 lung cancer cells by targeting CCND1

    International Nuclear Information System (INIS)

    Highlights: • We examined the level of miR-490-3p in A549 lung cancer cells compared with normal bronchial epithelial cell line. • We are the first to show the function of miR-490-3p in A549 lung cancer cells. • We demonstrate CCND1 may be one of the targets of miR-490-3p. - Abstract: MicroRNAs (miRNAs) are small non-coding RNAs that negatively regulate the translation of messenger RNAs by binding their 3′-untranslated region (3′UTR). In this study, we found that miR-490-3p is significantly down-regulated in A549 lung cancer cells compared with the normal bronchial epithelial cell line. To better characterize the role of miR-490-3p in A549 cells, we performed a gain-of-function analysis by transfecting the A549 cells with chemically synthesized miR-490-3P mimics. Overexpression of miR-490-3P evidently inhibits cell proliferation via G1-phase arrest. We also found that forced expression of miR-490-3P decreased both mRNA and protein levels of CCND1, which plays a key role in G1/S phase transition. In addition, the dual-luciferase reporter assays indicated that miR-490-3P directly targets CCND1 through binding its 3′UTR. These findings indicated miR-490-3P could be a potential suppressor of cellular proliferation

  14. Impacts of microRNA gene polymorphisms on the susceptibility of environmental factors leading to carcinogenesis in oral cancer.

    Directory of Open Access Journals (Sweden)

    Yin-Hung Chu

    Full Text Available BACKGROUND: MicroRNAs (miRNAs have been regarded as a critical factor in targeting oncogenes or tumor suppressor genes in tumorigenesis. The genetic predisposition of miRNAs-signaling pathways related to the development of oral squamous cell carcinoma (OSCC remains unresolved. This study examined the associations of polymorphisms with four miRNAs with the susceptibility and clinicopathological characteristics of OSCC. METHODOLOGY/PRINCIPAL FINDINGS: A total of 895 male subjects, including 425 controls and 470 male oral cancer patients, were selected. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP and real-time PCR were used to analyze miRNA146a, miRNA196, miRNA499 and miRNA149 genetic polymorphisms between the control group and the case group. This study determined that a significant association of miRNA499 with CC genotype, as compared to the subjects with TT genotype, had a higher risk (AOR = 4.52, 95% CI = 1.24-16.48 of OSCC. Moreover, an impact of those four miRNAs gene polymorphism on the susceptibility of betel nut and tobacco consumption leading to oral cancer was also revealed. We found a protective effect between clinical stage development (AOR = 0.58, 95% CI = 0.36-0.94 and the tumor size growth (AOR = 0.47, 95% CI = 0.28-0.79 in younger patients (age<60. CONCLUSIONS: Our results suggest that genetic polymorphism of miRNA499 is associated with oral carcinogenesis, and the interaction of the miRNAs genetic polymorphism and environmental carcinogens is also related to an increased risk of oral cancer in Taiwanese.

  15. MicroRNA-222 Controls Human Pancreatic Cancer Cell Line Capan-2 Proliferation by P57 Targeting

    Science.gov (United States)

    Zhao, Yingying; Wang, Yuqiong; Yang, Yuefeng; Liu, Jingqi; Song, Yang; Cao, Yan; Chen, Xiaoyu; Yang, Wenzhuo; Wang, Fei; Gao, Jun; Li, Zhaoshen; Yang, Changqing

    2015-01-01

    Pancreatic cancer (PC) is one of the most common cancers and has a poor prognosis due to late diagnosis and ineffective therapeutic multimodality. MicroRNAs (miRNAs, miRs) are a group of non-coding, small RNAs with active biological activities. In our investigation, human pancreatic cancer cell line Capan-2 were transfected with miR-222 mimics, inhibitors or their negative controls. Cell proliferation was assessed by Cell Counting Kit-8 (CCK-8), EdU incorporation assay and cell cycle determination by flow cytometry. MiR-222 and putative target gene expression levels including p27, p57 and PTEN were determined using quantitative reverse transcription polymerase chain reactions and Western blotting. Our results showed that miR-222 could lead to increased vitality and proliferative rate of Capan-2 cells, and also higher S-phase and lower G1-phase of cell cycle. Further, we found p57 at protein level, but not p27 nor PTEN, was regulated by miR-222 in Capan-2 cells. Finally, we co-transfected miR-222 inhibitor and p57 si-RNA into Capan-2 cells, and found that proliferation-suppressing effects of miR-222 inhibitor on Capan-2 cells could be partially reversed by silencing p57. Our results indicate that miR-222 controls Capan-2 cell proliferation by targeting p57. This study provides a novel idea for developing effective therapeutic strategy for PC patients through inhibiting miR-222. PMID:26535064

  16. An expression meta-analysis of predicted microRNA targets identifies a diagnostic signature for lung cancer

    Directory of Open Access Journals (Sweden)

    Liang Yu

    2008-12-01

    Full Text Available Abstract Background Patients diagnosed with lung adenocarcinoma (AD and squamous cell carcinoma (SCC, two major histologic subtypes of lung cancer, currently receive similar standard treatments, but resistance to adjuvant chemotherapy is prevalent. Identification of differentially expressed genes marking AD and SCC may prove to be of diagnostic value and help unravel molecular basis of their histogenesis and biologies, and deliver more effective and specific systemic therapy. Methods MiRNA target genes were predicted by union of miRanda, TargetScan, and PicTar, followed by screening for matched gene symbols in NCBI human sequences and Gene Ontology (GO terms using the PANTHER database that was also used for analyzing the significance of biological processes and pathways within each ontology term. Microarray data were extracted from Gene Expression Omnibus repository, and tumor subtype prediction by gene expression used Prediction Analysis of Microarrays. Results Computationally predicted target genes of three microRNAs, miR-34b/34c/449, that were detected in human lung, testis, and fallopian tubes but not in other normal tissues, were filtered by representation of GO terms and their ability to classify lung cancer subtypes, followed by a meta-analysis of microarray data to classify AD and SCC. Expression of a minimal set of 17 predicted miR-34b/34c/449 target genes derived from the developmental process GO category was identified from a training set to classify 41 AD and 17 SCC, and correctly predicted in average 87% of 354 AD and 82% of 282 SCC specimens from total 9 independent published datasets. The accuracy of prediction still remains comparable when classifying 103 AD and 79 SCC samples from another 4 published datasets that have only 14 to 16 of the 17 genes available for prediction (84% and 85% for AD and SCC, respectively. Expression of this signature in two published datasets of epithelial cells obtained at bronchoscopy from cigarette

  17. Pancreatic Cancer Cell Exosome-Mediated Macrophage Reprogramming and the Role of MicroRNAs 155 and 125b2 Transfection using Nanoparticle Delivery Systems.

    Science.gov (United States)

    Su, Mei-Ju; Aldawsari, Hibah; Amiji, Mansoor

    2016-01-01

    Exosomes are nano-sized endosome-derived small intraluminal vesicles, which are important facilitators of intercellular communication by transporting contents, such as protein, mRNA, and microRNAs, between neighboring cells, such as in the tumor microenvironment. The purpose of this study was to understand the mechanisms of exosomes-mediated cellular communication between human pancreatic cancer (Panc-1) cells and macrophages (J771.A1) using a Transwell co-culture system. Following characterization of exosome-mediated cellular communication and pro-tumoral baseline M2 macrophage polarization, the Panc-1 cells were transfected with microRNA-155 (miR-155) and microRNA-125b-2 (miR-125b2) expressing plasmid DNA using hyaluronic acid-poly(ethylene imine)/hyaluronic acid-poly(ethylene glycol) (HA-PEI/HA-PEG) self-assembling nanoparticle-based non-viral vectors. Our results show that upon successful transfection of Panc-1 cells, the exosome content was altered leading to differential communication and reprogramming of the J774.A1 cells to an M1 phenotype. Based on these results, genetic therapies targeted towards selective manipulation of tumor cell-derived exosome content may be very promising for cancer therapy. PMID:27443190

  18. Pancreatic Cancer Cell Exosome-Mediated Macrophage Reprogramming and the Role of MicroRNAs 155 and 125b2 Transfection using Nanoparticle Delivery Systems

    Science.gov (United States)

    Su, Mei-Ju; Aldawsari, Hibah; Amiji, Mansoor

    2016-01-01

    Exosomes are nano-sized endosome-derived small intraluminal vesicles, which are important facilitators of intercellular communication by transporting contents, such as protein, mRNA, and microRNAs, between neighboring cells, such as in the tumor microenvironment. The purpose of this study was to understand the mechanisms of exosomes-mediated cellular communication between human pancreatic cancer (Panc-1) cells and macrophages (J771.A1) using a Transwell co-culture system. Following characterization of exosome-mediated cellular communication and pro-tumoral baseline M2 macrophage polarization, the Panc-1 cells were transfected with microRNA-155 (miR-155) and microRNA-125b-2 (miR-125b2) expressing plasmid DNA using hyaluronic acid-poly(ethylene imine)/hyaluronic acid-poly(ethylene glycol) (HA-PEI/HA-PEG) self-assembling nanoparticle-based non-viral vectors. Our results show that upon successful transfection of Panc-1 cells, the exosome content was altered leading to differential communication and reprogramming of the J774.A1 cells to an M1 phenotype. Based on these results, genetic therapies targeted towards selective manipulation of tumor cell-derived exosome content may be very promising for cancer therapy. PMID:27443190

  19. MicroRNA-429 induces tumorigenesis of human non-small cell lung cancer cells and targets multiple tumor suppressor genes

    Energy Technology Data Exchange (ETDEWEB)

    Lang, Yaoguo; Xu, Shidong; Ma, Jianqun; Wu, Jun [Department of Thoracic Surgery, Harbin Medical University Cancer Hospital, 150 Haping Road, Harbin, Heilongjiang 150081 (China); Jin, Shi; Cao, Shoubo [Department of Medical Oncology, Harbin Medical University Cancer Hospital, 150 Haping Road, Harbin, Heilongjiang 150081 (China); Yu, Yan, E-mail: yuyan@hrbmu.edu.cn [Department of Medical Oncology, Harbin Medical University Cancer Hospital, 150 Haping Road, Harbin, Heilongjiang 150081 (China)

    2014-07-18

    Highlights: • MiR-429 expression is upregulated in non-small cell lung cancer (NSCLC). • MiR-429 inhibits PTEN, RASSF8 and TIMP2 expression. • MiR-429 promotes metastasis and proliferation. • We report important regulatory mechanisms involved in NSCLC progression. • MiR-429 is a potential therapeutic target and diagnostic marker. - Abstract: Lung cancer is the major cause of cancer death globally. MicroRNAs are evolutionally conserved small noncoding RNAs that are critical for the regulation of gene expression. Aberrant expression of microRNA (miRNA) has been implicated in cancer initiation and progression. In this study, we demonstrated that the expression of miR-429 are often upregulated in non-small cell lung cancer (NSCLC) compared with normal lung tissues, and its expression level is also increased in NSCLC cell lines compared with normal lung cells. Overexpression of miR-429 in A549 NSCLC cells significantly promoted cell proliferation, migration and invasion, whereas inhibition of miR-429 inhibits these effects. Furthermore, we demonstrated that miR-429 down-regulates PTEN, RASSF8 and TIMP2 expression by directly targeting the 3′-untranslated region of these target genes. Taken together, our results suggest that miR-429 plays an important role in promoting the proliferation and metastasis of NSCLC cells and is a potential target for NSCLC therapy.

  20. MicroRNA-429 induces tumorigenesis of human non-small cell lung cancer cells and targets multiple tumor suppressor genes

    International Nuclear Information System (INIS)

    Highlights: • MiR-429 expression is upregulated in non-small cell lung cancer (NSCLC). • MiR-429 inhibits PTEN, RASSF8 and TIMP2 expression. • MiR-429 promotes metastasis and proliferation. • We report important regulatory mechanisms involved in NSCLC progression. • MiR-429 is a potential therapeutic target and diagnostic marker. - Abstract: Lung cancer is the major cause of cancer death globally. MicroRNAs are evolutionally conserved small noncoding RNAs that are critical for the regulation of gene expression. Aberrant expression of microRNA (miRNA) has been implicated in cancer initiation and progression. In this study, we demonstrated that the expression of miR-429 are often upregulated in non-small cell lung cancer (NSCLC) compared with normal lung tissues, and its expression level is also increased in NSCLC cell lines compared with normal lung cells. Overexpression of miR-429 in A549 NSCLC cells significantly promoted cell proliferation, migration and invasion, whereas inhibition of miR-429 inhibits these effects. Furthermore, we demonstrated that miR-429 down-regulates PTEN, RASSF8 and TIMP2 expression by directly targeting the 3′-untranslated region of these target genes. Taken together, our results suggest that miR-429 plays an important role in promoting the proliferation and metastasis of NSCLC cells and is a potential target for NSCLC therapy

  1. Androgen receptor regulated microRNA miR-182-5p promotes prostate cancer progression by targeting the ARRDC3/ITGB4 pathway.

    Science.gov (United States)

    Yao, Jingjing; Xu, Chen; Fang, Ziyu; Li, Yaoming; Liu, Houqi; Wang, Yue; Xu, Chuanliang; Sun, Yinghao

    2016-05-20

    MicroRNAs (miRNAs) are important endogenous gene regulators that play key roles in prostate cancer development and metastasis. However, specific miRNA expression patterns in prostate cancer tissues from Chinese patients remain largely unknown. In this study, we compared miRNA expression patterns in 65 pairs of prostate cancer and para-cancer tissues by RNA sequencing and found that miR-182-5p was the most up-regulated miRNA in prostate cancer tissues. The result was validated using realtime PCR in 18 pairs of prostate cancer and para-cancer tissues. In in vitro analysis, it was confirmed that miR-182-5p promotes prostate cancer cell proliferation, invasion and migration and inhibit apoptosis. In addition, the androgen receptor directly regulated the transcription of miR-182-5p, which could target to the 3'UTR of ARRDC3 mRNA and affect the expression of ARRDC3 and its downstream gene ITGB4. For the in vivo experiment, miR-182-5p overexpression also promoted the growth and progression of prostate cancer tumors. In this regard, we suggest that miR-182-5p may be a key androgen receptor-regulated factor that contributes to the development and metastasis of Chinese prostate cancers and may be a potential target for the early diagnosis and therapeutic studies of prostate cancer. PMID:27109471

  2. Metformin inhibits lung cancer cells proliferation through repressing microRNA-222.

    Science.gov (United States)

    Wang, Yuqi; Dai, Weimin; Chu, Xiangyang; Yang, Bo; Zhao, Ming; Sun, Yu'e

    2013-12-01

    Metformin, which is commonly used as an oral anti-hyperglycemic agent of the biguanide family, may reduce cancer risk and improve prognosis. However, the mechanism by which metformin affects various cancers, including lung cancer, remains unknown. MiR-222 induces cell growth and cell cycle progression via direct targeting of p27, p57 and PTEN in cancer cells. In the present study, we used A549 and NCI-H358 human lung cancer cell lines to study the effects and mechanisms of metformin. Metformin treatment reduced expression of miR-222 in these cells (p metformin. Therefore, these data provide novel evidence for a mechanism that may contribute to the anti-neoplastic effects of metformin suggested by recent population studies and justifying further work to explore potential roles for it in lung cancer treatment. PMID:23974492

  3. MicroRNAs: Promising chemoresistance biomarkers in gastric cancer with diagnostic and therapeutic potential

    OpenAIRE

    Matuszcak, Christiane; Haier, Joerg; Hummel, Richard; Lindner, Kirsten

    2014-01-01

    Gastric cancer (GC) is the fourth most common cancer worldwide and ranks second in global cancer mortality statistics. Perioperative chemotherapy plays an important role in the management and treatment of advanced stage disease. However, response to chemotherapy varies widely, with some patients presenting no or only minor response to treatment. Hence, chemotherapy resistance is a major clinical problem that impacts on outcome. Unfortunately, to date there are no reliable biomarkers available...

  4. Network regularised Cox regression and multiplex network models to predict disease comorbidities and survival of cancer.

    Science.gov (United States)

    Xu, Haoming; Moni, Mohammad Ali; Liò, Pietro

    2015-12-01

    In cancer genomics, gene expression levels provide important molecular signatures for all types of cancer, and this could be very useful for predicting the survival of cancer patients. However, the main challenge of gene expression data analysis is high dimensionality, and microarray is characterised by few number of samples with large number of genes. To overcome this problem, a variety of penalised Cox proportional hazard models have been proposed. We introduce a novel network regularised Cox proportional hazard model and a novel multiplex network model to measure the disease comorbidities and to predict survival of the cancer patient. Our methods are applied to analyse seven microarray cancer gene expression datasets: breast cancer, ovarian cancer, lung cancer, liver cancer, renal cancer and osteosarcoma. Firstly, we applied a principal component analysis to reduce the dimensionality of original gene expression data. Secondly, we applied a network regularised Cox regression model on the reduced gene expression datasets. By using normalised mutual information method and multiplex network model, we predict the comorbidities for the liver cancer based on the integration of diverse set of omics and clinical data, and we find the diseasome associations (disease-gene association) among different cancers based on the identified common significant genes. Finally, we evaluated the precision of the approach with respect to the accuracy of survival prediction using ROC curves. We report that colon cancer, liver cancer and renal cancer share the CXCL5 gene, and breast cancer, ovarian cancer and renal cancer share the CCND2 gene. Our methods are useful to predict survival of the patient and disease comorbidities more accurately and helpful for improvement of the care of patients with comorbidity. Software in Matlab and R is available on our GitHub page: https://github.com/ssnhcom/NetworkRegularisedCox.git. PMID:26611766

  5. MicroRNA-100 suppresses the migration and invasion of breast cancer cells by targeting FZD-8 and inhibiting Wnt/β-catenin signaling pathway.

    Science.gov (United States)

    Jiang, Qian; He, Miao; Guan, Shu; Ma, Mengtao; Wu, Huizhe; Yu, Zhaojin; Jiang, Longyang; Wang, Yan; Zong, Xingyue; Jin, Feng; Wei, Minjie

    2016-04-01

    Wnt/β-catenin signaling pathway plays a major role in the cancer metastasis. Several microRNAs (miRNAs) are contributed to the inhibition of breast cancer metastasis. Here, we attempted to find novel targets and mechanisms of microRNA-100 (miR-100) in regulating the migration and invasion of breast cancer cells. In this study, we found that miR-100 expression was downregulated in human breast cancer tissues and cell lines. The overexpression of miR-100 inhibited the migration and invasion of MDA-MB-231 breast cancer cells. Inversely, the downregulation of miR-100 increased the migration and invasion of MCF-7 breast cancer cells. Furthermore, FZD-8, a receptor of Wnt/β-catenin signaling pathway, was demonstrated a direct target of miR-100. The overexpression of miR-100 decreased the expression levels not only FZD-8 but also the key components of Wnt/β-catenin pathway, including β-catenin, metalloproteniase-7 (MMP-7), T-cell factor-4 (TCF-4), and lymphoid enhancing factor-1 (LEF-1), and increased the protein expression levels of GSK-3β and p-GSK-3β in MDA-MB-231 cells, and the transfection of miR-100 inhibitor in MCF-7 cells showed the opposite effects. In addition, the expression of miR-100 was negatively correlated with the FZD-8 expression in human breast cancer tissues. Overall, these findings suggest that miR-100 suppresses the migration and invasion of breast cancer cells by targeting FZD-8 and inhibiting Wnt/β-catenin signaling pathway and manipulation of miR-100 may provide a promoting therapeutic strategy for cancer breast treatment. PMID:26537584

  6. Emerging Roles of MicroRNAs in EGFR-Targeted Therapies for Lung Cancer

    Directory of Open Access Journals (Sweden)

    Fei Han

    2015-01-01

    Full Text Available Lung cancer is a leading cause of cancer mortality worldwide. Several molecular pathways underlying mechanisms of this disease have been partly elucidated, among which the epidermal growth factor receptor (EGFR pathway is one of the well-known signaling cascades that plays a critical role in tumorigenesis. Dysregulation of the EGFR signaling is frequently found in lung cancer. The strategies to effectively inhibit EGFR signaling pathway have been mounted for developing anticancer therapeutic agents. However, most anti-EGFR-targeted agents fail to repress cancer progression because of developing drug-resistance. Therefore, studies of the mechanisms underpinning the resistance toward anti-EGFR agents may provide important findings for lung cancer treatment using anti-EGFR therapies. Recently, increasing numbers of miRNAs are correlated with the drug resistance of lung cancer cells to anti-EGFR agents, indicating that miRNAs may serve as novel targets and/or promising predictive biomarkers for anti-EGFR therapy. In this paper, we summarize the emerging role of miRNAs as regulators to modulate the EGFR signaling and the resistance of lung cancer cells to anti-EGFR therapy. We also highlight the evidence supporting the use of miRNAs as biomarkers for response to anti-EGFR agents and as novel therapeutic targets to circumvent the resistance of lung cancer cells to EGFR inhibitors.

  7. microRNA-143 down-regulates Hexokinase 2 in colon cancer cells

    DEFF Research Database (Denmark)

    Gregersen, Lea Haarup; Jacobsen, Anders; Frankel, Lisa;

    2012-01-01

    validated HK2 as a miR-143 target. Furthermore, our results indicate that miR-143 mediated down-regulation of HK2 affects glucose metabolism in colon cancer cells. We hypothesize that loss of miR-143-mediated repression of HK2 can promote glucose metabolism in cancer cells, contributing to the shift towards...

  8. MicroRNA-373 functions as an oncogene and targets YOD1 gene in cervical cancer

    International Nuclear Information System (INIS)

    miR-373 was reported to be elevated in several tumors; however, the role of miR-373 in cervical cancer has not been investigated. In this study we aimed to investigate the role of miR-373 in tumorigenicity of cervical cancer cells in vivo and in vitro. The expression of miR-373 was investigated using real-time reverse transcription-polymerase chain reaction assay in 45 cervical specimens and cervical cancer cell lines. The role of miR-373 in tumorigenicity of cervical cancer cells was assessed by cell proliferation, colony formation in vitro as well as tumor growth assays in vivo with the overexpression of miR-373 or gene silencing. The functional target gene of miR-373 in cervical cancer cells was identified using integrated bioinformatics analysis, gene expression arrays, and luciferase assay. We founded that the expression of miR-373 is upregulated in human cervical cancer tissues and cervical carcinoma cell lines when compared to the corresponding noncancerous tissues. Ectopic overexpression of miR-373 in human cervical cancer cells promoted cell growth in vitro and tumorigenicity in vivo, whereas silencing the expression of miR-373 decreased the rate of cell growth. YOD1 was identified as a direct and functional target of miR-373 in cervical cancer cells. Expression levels of miR-373 were inversely correlated with YOD1 levels in human cervical cancer tissues. RNAi-mediated knockdown of YOD1 phenocopied the proliferation-promoting effect of miR-373. Moreover, overexpression of YOD1 abrogated miR-373-induced proliferation of cervical cancer cells. These results demonstrate that miR-373 increases proliferation by directly targeting YOD1, a new potential therapeutic target in cervical cancer. - Highlights: • The expression of miR-373 is upregulated in human cervical cancer tissues. • miR-373 effects as oncogenic miRNA in cervical cancer in vitro and in vivo. • miR-373 increases proliferation of cervical cancer cells by directly targeting YOD1

  9. MicroRNA-373 functions as an oncogene and targets YOD1 gene in cervical cancer

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Luo-Qiao; Zhang, Yue; Yan, Huan; Liu, Kai-Jiang, E-mail: liukaijiang@126.com; Zhang, Shu, E-mail: drzhangshu@126.com

    2015-04-10

    miR-373 was reported to be elevated in several tumors; however, the role of miR-373 in cervical cancer has not been investigated. In this study we aimed to investigate the role of miR-373 in tumorigenicity of cervical cancer cells in vivo and in vitro. The expression of miR-373 was investigated using real-time reverse transcription-polymerase chain reaction assay in 45 cervical specimens and cervical cancer cell lines. The role of miR-373 in tumorigenicity of cervical cancer cells was assessed by cell proliferation, colony formation in vitro as well as tumor growth assays in vivo with the overexpression of miR-373 or gene silencing. The functional target gene of miR-373 in cervical cancer cells was identified using integrated bioinformatics analysis, gene expression arrays, and luciferase assay. We founded that the expression of miR-373 is upregulated in human cervical cancer tissues and cervical carcinoma cell lines when compared to the corresponding noncancerous tissues. Ectopic overexpression of miR-373 in human cervical cancer cells promoted cell growth in vitro and tumorigenicity in vivo, whereas silencing the expression of miR-373 decreased the rate of cell growth. YOD1 was identified as a direct and functional target of miR-373 in cervical cancer cells. Expression levels of miR-373 were inversely correlated with YOD1 levels in human cervical cancer tissues. RNAi-mediated knockdown of YOD1 phenocopied the proliferation-promoting effect of miR-373. Moreover, overexpression of YOD1 abrogated miR-373-induced proliferation of cervical cancer cells. These results demonstrate that miR-373 increases proliferation by directly targeting YOD1, a new potential therapeutic target in cervical cancer. - Highlights: • The expression of miR-373 is upregulated in human cervical cancer tissues. • miR-373 effects as oncogenic miRNA in cervical cancer in vitro and in vivo. • miR-373 increases proliferation of cervical cancer cells by directly targeting YOD1.

  10. Identification of bolting-related microRNAs and their targets reveals complex miRNA-mediated flowering-time regulatory networks in radish (Raphanus sativus L.)

    OpenAIRE

    Shanshan Nie; Liang Xu; Yan Wang; Danqiong Huang; Everlyne M. Muleke; Xiaochuan Sun; Ronghua Wang; Yang Xie; Yiqin Gong; Liwang Liu

    2015-01-01

    MicroRNAs (miRNAs) play vital regulatory roles in plant growth and development. The phase transition from vegetative growth to flowering is crucial in the life cycle of plants. To date, miRNA-mediated flowering regulatory networks remain largely unexplored in radish. In this study, two small RNA libraries from radish leaves at vegetative and reproductive stages were constructed and sequenced by Solexa sequencing. A total of 94 known miRNAs representing 21 conserved and 13 non-conserved miRNA ...

  11. Exosomal microRNA Biomarkers: Emerging Frontiers in Colorectal and Other Human Cancers.

    Science.gov (United States)

    Tovar-Camargo, Oscar A; Toden, Shusuke; Goel, Ajay

    2016-05-01

    Diagnostic strategies, particularly non-invasive blood-based screening approaches, are gaining increased attention for the early detection and attenuation of mortality associated with colorectal cancer (CRC). However, the majority of current screening approaches are inadequate at replacing the conventional CRC diagnostic procedures. Yet, due to technological advances and better understanding of molecular events underlying human cancer, a new category of biomarkers are on the horizon. Recent evidence indicates that cells release a distinct class of small vesicles called 'exosomes', which contain nucleic acids and proteins that reflect and typify host-cell molecular architecture. Intriguingly, exosomes released from cancer cells have a distinct genetic and epigenetic makeup, which allows them to undertake their tumorigenic function. From a clinical standpoint, these unique cancer-specific fingerprints present in exosomes appear to be detectable in a small amount of blood, making them very attractive substrates for developing cancer biomarkers, particularly noninvasive diagnostic approaches. PMID:26892862

  12. Possible role of Toxoplasma gondii in brain cancer through modulation of host microRNAs

    Directory of Open Access Journals (Sweden)

    Thirugnanam Sivasakthivel

    2013-02-01

    Full Text Available Abstract Background The obligate intracellular protozoan parasite Toxoplasma gondii infects humans and other warm-blooded animals and establishes a chronic infection in the central nervous system after invasion. Studies showing a positive correlation between anti-Toxoplasma antibodies and incidences of brain cancer have led to the notion that Toxoplasma infections increase the risk of brain cancer. However, molecular events involved in Toxoplasma induced brain cancers are not well understood. Presentation of the hypothesis Toxoplasma gains control of host cell functions including proliferation and apoptosis by channelizing parasite proteins into the cell cytoplasm and some of the proteins are targeted to the host nucleus. Recent studies have shown that Toxoplasma is capable of manipulating host micro RNAs (miRNAs, which play a central role in post-transcriptional regulation of gene expression. Therefore, we hypothesize that Toxoplasma promotes brain carcinogenesis by altering the host miRNAome using parasitic proteins and/or miRNAs. Testing the hypothesis The miRNA expression profiles of brain cancer specimens obtained from patients infected with Toxoplasma could be analyzed and compared with that of normal tissues as well as brain cancer tissues from Toxoplasma uninfected individuals to identify dysregulated miRNAs in Toxoplasma-driven brain cancer cells. Identified miRNAs will be further confirmed by studying cancer related miRNA profiles of the different types of brain cells before and after Toxoplasma infection using cell lines and experimental animals. Expected outcome The miRNAs specifically associated with brain cancers that are caused by Toxoplasma infection will be identified. Implications of the hypothesis Toxoplasma infection may promote initiation and progression of cancer by modifying the miRNAome in brain cells. If this hypothesis is true, the outcome of this research would lead to the development of novel biomarkers and

  13. MicroRNA in the immune system, microRNA as an immune system

    OpenAIRE

    Lu, Li-Fan; Liston, Adrian

    2009-01-01

    The advent of microRNA has potentially uncovered a new level of complexity to be considered for every biological process. Through the modulation of transcription and translation, microRNA alter the basal state of cells and the outcome of stimulatory events. The exact effect of the microRNA network and individual microRNA on cellular processes is only just starting to be dissected. In the immune system, microRNA appear to have a key role in the early differentiation and effector differentiatio...

  14. MicroRNA-16 Modulates HuR Regulation of Cyclin E1 in Breast Cancer Cells

    Directory of Open Access Journals (Sweden)

    Xun Guo

    2015-03-01

    Full Text Available RNA binding protein (RBPs and microRNAs (miRNAs or miRs are post-transcriptional regulators of gene expression that are implicated in development of cancers. Although their individual roles have been studied, the crosstalk between RBPs and miRNAs is under intense investigation. Here, we show that in breast cancer cells, cyclin E1 upregulation by the RBP HuR is through specific binding to regions in the cyclin E1 mRNA 3' untranslated region (3'UTR containing U-rich elements. Similarly, miR-16 represses cyclin E1, dependent on its cognate binding sites in the cyclin E1 3'UTR. Evidence in the literature indicates that HuR can regulate miRNA expression and recruit or dissociate RNA-induced silencing complexes (RISC. Despite this, miR-16 and HuR do not affect the other’s expression level or binding to the cyclin E1 3'UTR. While HuR overexpression partially blocks miR-16 repression of a reporter mRNA containing the cyclin E1 3'UTR, it does not block miR-16 repression of endogenous cyclin E1 mRNA. In contrast, miR-16 blocks HuR-mediated upregulation of cyclin E1. Overall our results suggest that miR-16 can override HuR upregulation of cyclin E1 without affecting HuR expression or association with the cyclin E1 mRNA.

  15. Identification of colorectal cancer-restricted microRNAs and their target genes based on high-throughput sequencing data.

    Science.gov (United States)

    Chang, Jing; Huang, Liya; Cao, Qing; Liu, Fang

    2016-01-01

    To identify potential key microRNAs (miRNAs) and their target genes for colorectal cancer (CRC). High-throughput sequencing data of miRNA expression and gene expression (ID: GSE46622) were downloaded from Gene Expression Omnibus, including matched colon tumor, normal colon epithelium, and liver metastasis tissues from eight CRC patients. Paired t-test and NOISeq separately were utilized to identify differentially expressed miRNAs (DE-miRNAs) and genes. Then, target genes with differential expression and opposite expression trends were identified for DE-miRNAs. Combined with tumor suppressor gene, tumor-associated gene, and TRANSFAC databases, CRC-restricted miRNAs were screened out based on miRNA-target pairs. Compared with normal tissues, there were 56 up- and 37 downregulated miRNAs in metastasis tissues, as well as eight up- and 30 downregulated miRNAs in tumor tissues. miRNA-1 was downregulated in tumor and metastasis tissues, while its target oncogenes TWIST1 and GATA4 were upregulated. Besides, miRNA-let-7f-1-3p was downregulated in tumor tissues, which also targeted TWIST1. In addition, miRNA-133b and miRNA-4458 were downregulated in tumor tissues, while their common target gene DUSP9 was upregulated. Conversely, miRNA-450-b-3p was upregulated in metastasis tissues, while its target tumor suppressor gene CEACAM7 showed downregulation. The identified CRC-restricted miRNAs might be implicated in cancer progression via their target genes, suggesting their potential usage in CRC treatment. PMID:27069368

  16. Identification of a microRNA expression signature for chemoradiosensitivity of colorectal cancer cells, involving miRNAs-320a, -224, -132 and let7g

    International Nuclear Information System (INIS)

    Background and purpose: Preoperative chemoradiotherapy (CRT) represents the standard treatment for locally advanced rectal cancer. Tumor response and progression vary considerably. MicroRNAs represent master regulators of gene expression, and may therefore contribute to this diversity. Material and methods: Genome-wide microRNA (miRNA) profiling was performed for 12 colorectal cancer (CRC) cell lines and an individual in vitro signature of chemoradiosensitivity was established. Functional relevance of selected miRNAs was established by transfecting miRNA-mimics into SW480 and SW837 cells. The prognostic value of selected miRNAs was assessed in 128 pretherapeutic patient biopsies. Results: Thirty-six miRNAs were identified to significantly correlate with sensitivity to CRT (Q < 0.05) including miR-320a and other miRNAs involved in the MAPK-, TGF- and Wnt-pathway. Transfection of selected miRNAs (let-7g, miR-132, miR-224, miR-320a) each induced a shift of sensitivity. High expression of let-7g was associated with a good prognosis in rectal cancer patients (P = 0.03). Conclusions: This is the first report of a miRNA expression signature for in vitro chemoradiosensitivity of CRC cell lines. Many of the identified miRNAs have not been linked to the response to CRT and may represent potential molecular targets to sensitize resistant cancers. If further validated, let7g expression may serve as predictive biomarker

  17. Electrochemical based detection of microRNA, mir21 in breast cancer cells.

    Science.gov (United States)

    Kilic, Tugba; Topkaya, Seda Nur; Ozkan Ariksoysal, Dilsat; Ozsoz, Mehmet; Ballar, Petek; Erac, Yasemin; Gozen, Oguz

    2012-01-01

    In this work, a novel electrochemical microRNA (miRNA) detection method based on enzyme amplified biosensing of mir21 from cell lysate of total RNA was demonstrated. The proposed enzymatic detection method was detailed and compared with the conventional guanine oxidation based assay in terms of detection limit and specificity. For the detection of mir21, capture probes and/or cell lysates were covalently attached onto the pencil graphite electrode (PGE) by coupling agents of N-(dimethylamino)propyl-N'-ethylcarbodiimide hydrochloride (EDC) and N-hydroxysulfosuccinimide (NHS). Having immobilized the capture probe onto the surface of PGE, hybridization was achieved with a biotinylated (from its 3' end) complementary target. Extravidin labeled alkaline phosphatase (Ex-Ap) binds to the biotinylated target due to the interaction between biotin-avidin and the enzyme converts electro-inactive alpha naphtyl phosphate (the substrate) to electro-active alpha naphtol (α-NAP, the product). α-NAP was oxidized at +0.23 V vs Ag/AgCl and this signal was measured by Differential Pulse Voltammetry (DPV). The signals obtained from α-NAP oxidation were compared for the probe and hybrid DNA. The specificity of the designed biosensor was proved by using non-complementary sequences instead of complementary sequences and the detection limit of the assay was calculated to be 6 pmol for cell lysates. PMID:22776181

  18. BIOSYNTHESIS OF microRNAs AND THEIR ROLE IN GENE EXPRESSION PROFILING IN BREAST CANCER

    Directory of Open Access Journals (Sweden)

    Leonardo Barcelos de Paula

    2011-01-01

    Full Text Available The aggressive nature of breast cancer in young women may be related to the occurrence of mutations in the BRCA1/BRCA2 genes responsible for DNA repair. Despite of cases are associated with and without a family history of breast and ovarian cancer such changes are present in only a small percentage of cases, which corresponds to 80-10% of patients with familial breast cancer and 3.2-10.6% of women withbreast cancer non-familial (sporadic. The penetrance rate of this variability is not well understood today, but we know that reproductive factors, risks posed by particular mutations and other genetic modifiers The expression profile of miRNAs can also reveal changes in the regulatory processes that distinguish the appearance of cancer familial and sporadic breast cancer in young patients. miRNAs have been described as related to the aggressiveness of breast cancer and the sensitivity of human mammary tumor strains to antiestrogen. Such evidence indicates that the molecular mechanisms responsible for the aggressive behavior of breast carcinoma in young women has not been sufficiently clarified.

  19. microRNA-21 Governs TORC1 Activation in Renal Cancer Cell Proliferation and Invasion

    OpenAIRE

    Dey, Nirmalya; Das, Falguni; Ghosh-Choudhury, Nandini; Mandal, Chandi Charan; Parekh, Dipen J.; Block, Karen; Kasinath, Balakuntalam S.; Abboud, Hanna E.; Choudhury, Goutam Ghosh

    2012-01-01

    Metastatic renal cancer manifests multiple signatures of gene expression. Deviation in expression of mature miRNAs has been linked to human cancers. Importance of miR-21 in renal cell carcinomas is proposed from profiling studies using tumor tissue samples. However, the role of miR-21 function in causing renal cancer cell proliferation and invasion has not yet been shown. Using cultured renal carcinoma cells, we demonstrate enhanced expression of mature miR-21 along with pre-and pri-miR-21 by...

  20. MicroRNAs: short non-coding players in cancer chemoresistance.

    Science.gov (United States)

    Donzelli, Sara; Mori, Federica; Biagioni, Francesca; Bellissimo, Teresa; Pulito, Claudio; Muti, Paola; Strano, Sabrina; Blandino, Giovanni

    2014-01-01

    Chemoresistance is one of the main problems in the therapy of cancer. There are a number of different molecular mechanisms through which a cancer cell acquires resistance to a specific treatment, such as alterations in drug uptake, drug metabolism and drug targets. There are several lines of evidence showing that miRNAs are involved in drug sensitivity of cancer cells in different tumor types and by different treatments. In this review, we provide an overview of the more recent and significant findings on the role of miRNAs in cancer cell drug resistance. In particular, we focus on specific miRNA mechanisms of action that in various steps lead from drug cell sensitivity to drug cell resistance. We also provide evidence on how miRNA profiling may unveil relevant predictive biomarkers for therapy outcomes. PMID:26056584

  1. Circulating microRNAs as Prognostic and Predictive Biomarkers in Patients with Colorectal Cancer

    OpenAIRE

    Jakob Vasehus Schou; Julia Sidenius Johansen; Dorte Nielsen; Simona Rossi

    2016-01-01

    MiRNAs are suggested as promising cancer biomarkers. They are stable and extractable from a variety of clinical tissue specimens (fresh frozen or formalin fixed paraffin embedded tissue) and a variety of body fluids (e.g., blood, urine, saliva). However, there are several challenges that need to be solved, considering their potential as biomarkers in cancer, such as lack of consistency between biomarker panels in independent studies due to lack of standardized sample handling and processing, ...

  2. Potential Diagnostic, Prognostic and Therapeutic Targets of MicroRNAs in Human Gastric Cancer

    OpenAIRE

    Ming-Ming Tsai; Chia-Siu Wang; Chung-Ying Tsai; Hsiang-Wei Huang; Hsiang-Cheng Chi; Yang-Hsiang Lin; Pei-Hsuan Lu; Kwang-Huei Lin

    2016-01-01

    Human gastric cancer (GC) is characterized by a high incidence and mortality rate, largely because it is normally not identified until a relatively advanced stage owing to a lack of early diagnostic biomarkers. Gastroscopy with biopsy is the routine method for screening, and gastrectomy is the major therapeutic strategy for GC. However, in more than 30% of GC surgical patients, cancer has progressed too far for effective medical resection. Thus, useful biomarkers for early screening or detect...

  3. MicroRNAs transported by exosomes in body fluids as mediators of intercellular communication in cancer

    OpenAIRE

    Salido-Guadarrama I; Romero-Cordoba S; Peralta-Zaragoza O; Hidalgo-Miranda A; Rodríguez-Dorantes M

    2014-01-01

    Iván Salido-Guadarrama,1 Sandra Romero-Cordoba,1 Oscar Peralta-Zaragoza,2 Alfredo Hidalgo-Miranda,1 Mauricio Rodríguez-Dorantes1 1Oncogenomics Laboratory, National Institute of Genomics Medicine, Mexico City, Mexico; 2Direction of Chronic Infections and Cancer, Research Center in Infectious Diseases, National Institute of Public Health, Cuernavaca, Morelos, Mexico Abstract: Cancer-cell communication is an important and complex process, achieved through a diversity of me...

  4. Human papilloma virus, DNA methylation and microRNA expression in cervical cancer (Review)

    OpenAIRE

    JIMÉNEZ-WENCES, HILDA; Peralta-Zaragoza, Oscar; Fernández-Tilapa, Gloria

    2014-01-01

    Cancer is a complex disease caused by genetic and epigenetic abnormalities that affect gene expression. The progression from precursor lesions to invasive cervical cancer is influenced by persistent human papilloma virus (HPV) infection, which induces changes in the host genome and epigenome. Epigenetic alterations, such as aberrant miRNA expression and changes in DNA methylation status, favor the expression of oncogenes and the silencing of tumor-suppressor genes. Given that some miRNA genes...

  5. Metformin inhibits cell growth by upregulating microRNA-26a in renal cancer cells.

    Science.gov (United States)

    Yang, Feng-Qiang; Wang, Ji-Jiao; Yan, Jia-Sheng; Huang, Jian-Hua; Li, Wei; Che, Jian-Ping; Wang, Guang-Chun; Liu, Min; Zheng, Jun-Hua

    2014-01-01

    Accumulating evidence suggests that metformin, a biguanide class of anti-diabetic drugs, possesses anti-cancer properties and may reduce cancer risk and improve prognosis. However, the mechanism by which metformin affects various cancers, including renal cancer still unknown. MiR-26a induces cell growth, cell cycle and cell apoptosis progression via direct targeting of Bcl-2, clyclin D1 and PTEN in cancer cells. In the present study, we used 786-O human renal cancer cell lines to study the effects and mechanisms of metformin. Metformin treatment inhibited RCC cells proliferation by increasing expression of miR-26a in 786-O cells (P metformin. Also over-expression of miR-26a can inhibited cell proliferation by down-regulating Bcl-2, cyclin D1 and up-regulating PTEN expression. Therefore, these data for the first time provide novel evidence for a mechanism that the anticancer activities of metformin are due to upregulation of miR-26a and affect its downstream target gene. PMID:25419360

  6. The Northern Appalachia Cancer Network: Changing Cancer Research, Changing People's Lives

    Science.gov (United States)

    Lengerich, Eugene J.; Kluhsman, Brenda C.; Bencivenga, Marcyann M.; Lesko, Samuel M.; Garcia-Dominic, Oralia; Aumiller, Betsy B.; Anderson, Marcia

    2010-01-01

    The Northern Appalachia Cancer Network (NACN) is a community-academic partnership to develop, implement, and evaluate evidence-based interventions intended to reduce the burden of cancer in Appalachian Pennsylvania and New York. The NACN began in 1992 as a loose network of community coalitions intended to implement local programs for cancer…

  7. Discovering cancer genes by integrating network and functional properties

    Directory of Open Access Journals (Sweden)

    Davis David P

    2009-09-01

    Full Text Available Abstract Background Identification of novel cancer-causing genes is one of the main goals in cancer research. The rapid accumulation of genome-wide protein-protein interaction (PPI data in humans has provided a new basis for studying the topological features of cancer genes in cellular networks. It is important to integrate multiple genomic data sources, including PPI networks, protein domains and Gene Ontology (GO annotations, to facilitate the identification of cancer genes. Methods Topological features of the PPI network, as well as protein domain compositions, enrichment of gene ontology categories, sequence and evolutionary conservation features were extracted and compared between cancer genes and other genes. The predictive power of various classifiers for identification of cancer genes was evaluated by cross validation. Experimental validation of a subset of the prediction results was conducted using siRNA knockdown and viability assays in human colon cancer cell line DLD-1. Results Cross validation demonstrated advantageous performance of classifiers based on support vector machines (SVMs with the inclusion of the topological features from the PPI network, protein domain compositions and GO annotations. We then applied the trained SVM classifier to human genes to prioritize putative cancer genes. siRNA knock-down of several SVM predicted cancer genes displayed greatly reduced cell viability in human colon cancer cell line DLD-1. Conclusion Topological features of PPI networks, protein domain compositions and GO annotations are good predictors of cancer genes. The SVM classifier integrates multiple features and as such is useful for prioritizing candidate cancer genes for experimental validations.

  8. International network of cancer genome projects

    NARCIS (Netherlands)

    Hudson, Thomas J.; Anderson, Warwick; Aretz, Axel; Barker, Anna D.; Bell, Cindy; Bernabe, Rosa R.; Bhan, M. K.; Calvo, Fabien; Eerola, Iiro; Gerhard, Daniela S.; Guttmacher, Alan; Guyer, Mark; Hemsley, Fiona M.; Jennings, Jennifer L.; Kerr, David; Klatt, Peter; Kolar, Patrik; Kusuda, Jun; Lane, David P.; Laplace, Frank; Lu, Youyong; Nettekoven, Gerd; Ozenberger, Brad; Peterson, Jane; Rao, T. S.; Remacle, Jacques; Schafer, Alan J.; Shibata, Tatsuhiro; Stratton, Michael R.; Vockley, Joseph G.; Watanabe, Koichi; Yang, Huanming; Yuen, Matthew M. F.; Knoppers, M.; Bobrow, Martin; Cambon-Thomsen, Anne; Dressler, Lynn G.; Dyke, Stephanie O. M.; Joly, Yann; Kato, Kazuto; Kennedy, Karen L.; Nicolas, Pilar; Parker, Michael J.; Rial-Sebbag, Emmanuelle; Romeo-Casabona, Carlos M.; Shaw, Kenna M.; Wallace, Susan; Wiesner, Georgia L.; Zeps, Nikolajs; Lichter, Peter; Biankin, Andrew V.; Chabannon, Christian; Chin, Lynda; Clement, Bruno; de Alava, Enrique; Degos, Francoise; Ferguson, Martin L.; Geary, Peter; Hayes, D. Neil; Johns, Amber L.; Nakagawa, Hidewaki; Penny, Robert; Piris, Miguel A.; Sarin, Rajiv; Scarpa, Aldo; Shibata, Tatsuhiro; van de Vijver, Marc; Futreal, P. Andrew; Aburatani, Hiroyuki; Bayes, Monica; Bowtell, David D. L.; Campbell, Peter J.; Estivill, Xavier; Grimmond, Sean M.; Gut, Ivo; Hirst, Martin; Lopez-Otin, Carlos; Majumder, Partha; Marra, Marco; Nakagawa, Hidewaki; Ning, Zemin; Puente, Xose S.; Ruan, Yijun; Shibata, Tatsuhiro; Stratton, Michael R.; Stunnenberg, Hendrik G.; Swerdlow, Harold; Velculescu, Victor E.; Wilson, Richard K.; Xue, Hong H.; Yang, Liu; Spellman, Paul T.; Bader, Gary D.; Boutros, Paul C.; Campbell, Peter J.; Flicek, Paul; Getz, Gad; Guigo, Roderic; Guo, Guangwu; Haussler, David; Heath, Simon; Hubbard, Tim J.; Jiang, Tao; Jones, Steven M.; Li, Qibin; Lopez-Bigas, Nuria; Luo, Ruibang; Pearson, John V.; Puente, Xose S.; Quesada, Victor; Raphael, Benjamin J.; Sander, Chris; Shibata, Tatsuhiro; Speed, Terence P.; Stuart, Joshua M.; Teague, Jon W.; Totoki, Yasushi; Tsunoda, Tatsuhiko; Valencia, Alfonso; Wheeler, David A.; Wu, Honglong; Zhao, Shancen; Zhou, Guangyu; Stein, Lincoln D.; Guigo, Roderic; Hubbard, Tim J.; Joly, Yann; Jones, Steven M.; Lathrop, Mark; Lopez-Bigas, Nuria; Ouellette, B. F. Francis; Spellman, Paul T.; Teague, Jon W.; Thomas, Gilles; Valencia, Alfonso; Yoshida, Teruhiko; Kennedy, Karen L.; Axton, Myles; Dyke, Stephanie O. M.; Futreal, P. Andrew; Gunter, Chris; Guyer, Mark; McPherson, John D.; Miller, Linda J.; Ozenberger, Brad; Kasprzyk, Arek; Zhang, Junjun; Haider, Syed A.; Wang, Jianxin; Yung, Christina K.; Cross, Anthony; Liang, Yong; Gnaneshan, Saravanamuttu; Guberman, Jonathan; Hsu, Jack; Bobrow, Martin; Chalmers, Don R. C.; Hasel, Karl W.; Joly, Yann; Kaan, Terry S. H.; Kennedy, Karen L.; Knoppers, Bartha M.; Lowrance, William W.; Masui, Tohru; Nicolas, Pilar; Rial-Sebbag, Emmanuelle; Rodriguez, Laura Lyman; Vergely, Catherine; Yoshida, Teruhiko; Grimmond, Sean M.; Biankin, Andrew V.; Bowtell, David D. L.; Cloonan, Nicole; Defazio, Anna; Eshleman, James R.; Etemadmoghadam, Dariush; Gardiner, Brooke A.; Kench, James G.; Scarpa, Aldo; Sutherland, Robert L.; Tempero, Margaret A.; Waddell, Nicola J.; Wilson, Peter J.; Gallinger, Steve; Tsao, Ming-Sound; Shaw, Patricia A.; Petersen, Gloria M.; Mukhopadhyay, Debabrata; Chin, Lynda; DePinho, Ronald A.; Thayer, Sarah; Muthuswamy, Lakshmi; Shazand, Kamran; Beck, Timothy; Sam, Michelle; Timms, Lee; Ballin, Vanessa; Lu, Youyong; Ji, Jiafu; Zhang, Xiuqing; Chen, Feng; Hu, Xueda; Zhou, Guangyu; Yang, Qi; Tian, Geng; Zhang, Lianhai; Xing, Xiaofang; Li, Xianghong; Zhu, Zhenggang; Yu, Yingyan; Yu, Jun; Yang, Huanming; Lathrop, Mark; Tost, Joerg; Brennan, Paul; Holcatova, Ivana; Zaridze, David; Brazma, Alvis; Egevad, Lars; Prokhortchouk, Egor; Banks, Rosamonde Elizabeth; Uhlen, Mathias; Cambon-Thomsen, Anne; Viksna, Juris; Ponten, Fredrik; Skryabin, Konstantin; Stratton, Michael R.; Futreal, P. Andrew; Birney, Ewan; Borg, Ake; Borresen-Dale, Anne-Lise; Caldas, Carlos; Foekens, John A.; Martin, Sancha; Reis-Filho, Jorge S.; Richardson, Andrea L.; Sotiriou, Christos; Stunnenberg, Hendrik G.; Thomas, Gilles; van de Vijver, Marc; van't Veer, Laura; Birnbaum, Daniel; Blanche, Helene; Boucher, Pascal; Boyault, Sandrine; Chabannon, Christian; Gut, Ivo; Masson-Jacquemier, Jocelyne D.; Lathrop, Mark; Pauporte, Iris; Pivot, Xavier; Vincent-Salomon, Anne; Tabone, Eric; Theillet, Charles; Thomas, Gilles; Tost, Joerg; Treilleux, Isabelle; Bioulac-Sage, Paulette; Clement, Bruno; Decaens, Thomas; Degos, Francoise; Franco, Dominique; Gut, Ivo; Gut, Marta; Heath, Simon; Lathrop, Mark; Samuel, Didier; Thomas, Gilles; Zucman-Rossi, Jessica; Lichter, Peter; Eils, Roland; Brors, Benedikt; Korbel, Jan O.; Korshunov, Andrey; Landgraf, Pablo; Lehrach, Hans; Pfister, Stefan; Radlwimmer, Bernhard; Reifenberger, Guido; Taylor, Michael D.; von Kalle, Christof; Majumder, Partha P.; Sarin, Rajiv; Scarpa, Aldo; Pederzoli, Paolo; Lawlor, Rita T.; Delledonne, Massimo; Bardelli, Alberto; Biankin, Andrew V.; Grimmond, Sean M.; Gress, Thomas; Klimstra, David; Zamboni, Giuseppe; Shibata, Tatsuhiro; Nakamura, Yusuke; Nakagawa, Hidewaki; Kusuda, Jun; Tsunoda, Tatsuhiko; Miyano, Satoru; Aburatani, Hiroyuki; Kato, Kazuto; Fujimoto, Akihiro; Yoshida, Teruhiko; Campo, Elias; Lopez-Otin, Carlos; Estivill, Xavier; Guigo, Roderic; de Sanjose, Silvia; Piris, Miguel A.; Montserrat, Emili; Gonzalez-Diaz, Marcos; Puente, Xose S.; Jares, Pedro; Valencia, Alfonso; Himmelbaue, Heinz; Quesada, Victor; Bea, Silvia; Stratton, Michael R.; Futreal, P. Andrew; Campbell, Peter J.; Vincent-Salomon, Anne; Richardson, Andrea L.; Reis-Filho, Jorge S.; van de Vijver, Marc; Thomas, Gilles; Masson-Jacquemier, Jocelyne D.; Aparicio, Samuel; Borg, Ake; Borresen-Dale, Anne-Lise; Caldas, Carlos; Foekens, John A.; Stunnenberg, Hendrik G.; van't Veer, Laura; Easton, Douglas F.; Spellman, Paul T.; Martin, Sancha; Chin, Lynda; Collins, Francis S.; Compton, Carolyn C.; Ferguson, Martin L.; Getz, Gad; Gunter, Chris; Guyer, Mark; Hayes, D. Neil; Lander, Eric S.; Ozenberger, Brad; Penny, Robert; Peterson, Jane; Sander, Chris; Speed, Terence P.; Spellman, Paul T.; Wheeler, David A.; Wilson, Richard K.; Chin, Lynda; Knoppers, Bartha M.; Lander, Eric S.; Lichter, Peter; Stratton, Michael R.; Bobrow, Martin; Burke, Wylie; Collins, Francis S.; DePinho, Ronald A.; Easton, Douglas F.; Futreal, P. Andrew; Green, Anthony R.; Guyer, Mark; Hamilton, Stanley R.; Hubbard, Tim J.; Kallioniemi, Olli P.; Kennedy, Karen L.; Ley, Timothy J.; Liu, Edison T.; Lu, Youyong; Majumder, Partha; Marra, Marco; Ozenberger, Brad; Peterson, Jane; Schafer, Alan J.; Spellman, Paul T.; Stunnenberg, Hendrik G.; Wainwright, Brandon J.; Wilson, Richard K.; Yang, Huanming

    2010-01-01

    The International Cancer Genome Consortium (ICGC) was launched to coordinate large-scale cancer genome studies in tumours from 50 different cancer types and/or subtypes that are of clinical and societal importance across the globe. Systematic studies of more than 25,000 cancer genomes at the genomic

  9. Knockdown of astrocyte elevated gene-1 inhibits tumor growth and modifies microRNAs expression profiles in human colorectal cancer cells

    International Nuclear Information System (INIS)

    Highlights: • AEG-1 expression in CRC cell lines and down-regulation or upregulation of AEG-1 in vitro. • Knockdown of AEG-1 inhibits cell proliferation, colony formation and invasion. • Upregulation of AEG-1 enhances proliferation, invasion and colony formation. • Knockdown of AEG-1 accumulates G0/G1-phase cells and promotes apoptosis in CRC cells. • AEG-1 knockdown increases 5-FU cytotoxicity. - Abstract: Astrocyte elevated gene-1 (AEG-1), upregulated in various types of malignancies including colorectal cancer (CRC), has been reported to be associated with the carcinogenesis. MicroRNAs (miRNAs) are widely involved in the initiation and progression of cancer. However, the functional significance of AEG-1 and the relationship between AEG-1 and microRNAs in human CRC remains unclear. The aim of this study was to investigate whether AEG-1 could serve as a potential therapeutic target of human CRC and its possible mechanism. We adopted a strategy of ectopic overexpression or RNA interference to upregulate or downregulate expression of AEG-1 in CRC models. Their phenotypic changes were analyzed by Western blot, MTT and transwell matrix penetration assays. MicroRNAs expression profiles were performed using microarray analysis followed by validation using qRT-PCR. Knockdown of AEG-1 could significantly inhibit colon cancer cell proliferation, colony formation, invasion and promotes apoptosis. Conversely, upregulation of AEG-1 could significantly enhance cell proliferation, invasion and reduced apoptisis. AEG-1 directly contributes to resistance to chemotherapeutic drug. Targeted downregulation of AEG-1 might improve the expression of miR-181a-2∗, -193b and -193a, and inversely inhibit miR-31 and -9∗. Targeted inhibition of AEG-1 can lead to modification of key elemental characteristics, such as miRNAs, which may become a potential effective therapeutic strategy for CRC

  10. Knockdown of astrocyte elevated gene-1 inhibits tumor growth and modifies microRNAs expression profiles in human colorectal cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Sujun [East Department of Gastroenterology, Institute of Geriatrics, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong 510080 (China); Southern Medical University, Guangzhou, Guangdong 510515 (China); Wu, Binwen, E-mail: wubinwengd@aliyun.com [East Department of Gastroenterology, Institute of Geriatrics, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong 510080 (China); Li, Dongfeng; Zhou, Weihong; Deng, Gang; Zhang, Kaijun; Li, Youjia [East Department of Gastroenterology, Institute of Geriatrics, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong 510080 (China)

    2014-02-14

    Highlights: • AEG-1 expression in CRC cell lines and down-regulation or upregulation of AEG-1 in vitro. • Knockdown of AEG-1 inhibits cell proliferation, colony formation and invasion. • Upregulation of AEG-1 enhances proliferation, invasion and colony formation. • Knockdown of AEG-1 accumulates G0/G1-phase cells and promotes apoptosis in CRC cells. • AEG-1 knockdown increases 5-FU cytotoxicity. - Abstract: Astrocyte elevated gene-1 (AEG-1), upregulated in various types of malignancies including colorectal cancer (CRC), has been reported to be associated with the carcinogenesis. MicroRNAs (miRNAs) are widely involved in the initiation and progression of cancer. However, the functional significance of AEG-1 and the relationship between AEG-1 and microRNAs in human CRC remains unclear. The aim of this study was to investigate whether AEG-1 could serve as a potential therapeutic target of human CRC and its possible mechanism. We adopted a strategy of ectopic overexpression or RNA interference to upregulate or downregulate expression of AEG-1 in CRC models. Their phenotypic changes were analyzed by Western blot, MTT and transwell matrix penetration assays. MicroRNAs expression profiles were performed using microarray analysis followed by validation using qRT-PCR. Knockdown of AEG-1 could significantly inhibit colon cancer cell proliferation, colony formation, invasion and promotes apoptosis. Conversely, upregulation of AEG-1 could significantly enhance cell proliferation, invasion and reduced apoptisis. AEG-1 directly contributes to resistance to chemotherapeutic drug. Targeted downregulation of AEG-1 might improve the expression of miR-181a-2{sup ∗}, -193b and -193a, and inversely inhibit miR-31 and -9{sup ∗}. Targeted inhibition of AEG-1 can lead to modification of key elemental characteristics, such as miRNAs, which may become a potential effective therapeutic strategy for CRC.

  11. Gene network-based cancer prognosis analysis with sparse boosting

    OpenAIRE

    Ma, Shuangge; Huang, Yuan; Huang, Jian; Fang, Kuangnan

    2012-01-01

    High-throughput gene profiling studies have been extensively conducted, searching for markers associated with cancer development and progression. In this study, we analyse cancer prognosis studies with right censored survival responses. With gene expression data, we adopt the weighted gene co-expression network analysis (WGCNA) to describe the interplay among genes. In network analysis, nodes represent genes. There are subsets of nodes, called modules, which are tightly connected to each othe...

  12. Circulating microRNAs as Prognostic and Predictive Biomarkers in Patients with Colorectal Cancer

    Directory of Open Access Journals (Sweden)

    Jakob Vasehus Schou

    2016-06-01

    Full Text Available MiRNAs are suggested as promising cancer biomarkers. They are stable and extractable from a variety of clinical tissue specimens (fresh frozen or formalin fixed paraffin embedded tissue and a variety of body fluids (e.g., blood, urine, saliva. However, there are several challenges that need to be solved, considering their potential as biomarkers in cancer, such as lack of consistency between biomarker panels in independent studies due to lack of standardized sample handling and processing, use of inconsistent normalization approaches, and differences in patients populations. Focusing on colorectal cancer (CRC, divergent results regarding circulating miRNAs as prognostic or predictive biomarkers are reported in the literature. In the present review, we summarize the current data on circulating miRNAs as prognostic/predictive biomarkers in patients with localized and metastatic CRC (mCRC.

  13. Induction of cell proliferation and survival genes by estradiol-repressed microRNAs in breast cancer cells

    International Nuclear Information System (INIS)

    In estrogen responsive MCF-7 cells, estradiol (E2) binding to ERα leads to transcriptional regulation of genes involved in the control of cell proliferation and survival. MicroRNAs (miRNAs) have emerged as key post-transcriptional regulators of gene expression. The aim of this study was to explore whether miRNAs were involved in hormonally regulated expression of estrogen responsive genes. Western blot and QPCR were used to determine the expression of estrogen responsive genes and miRNAs respectively. Target gene expression regulated by miRNAs was validated by luciferase reporter assays and transfection of miRNA mimics or inhibitors. Cell proliferation was evaluated by MTS assay. E2 significantly induced bcl-2, cyclin D1 and survivin expression by suppressing the levels of a panel of miRNAs (miR-16, miR-143, miR-203) in MCF-7 cells. MiRNA transfection and luciferase assay confirmed that bcl-2 was regulated by miR-16 and miR-143, cyclinD1 was modulated by miR-16. Importantly, survivin was found to be targeted by miR-16, miR-143, miR-203. The regulatory effect of E2 can be either abrogated by anti-estrogen ICI 182, 780 and raloxifene pretreatment, or impaired by ERα siRNA, indicating the regulation is dependent on ERα. In order to investigate the functional significance of these miRNAs in estrogen responsive cells, miRNAs mimics were transfected into MCF-7 cells. It revealed that overexpression of these miRNAs significantly inhibited E2-induced cell proliferation. Further study of the expression of the miRNAs indicated that miR-16, miR-143 and miR-203 were highly expressed in triple positive breast cancer tissues, suggesting a potential tumor suppressing effect of these miRNAs in ER positive breast cancer. These results demonstrate that E2 induces bcl-2, cyclin D1 and survivin by orchestrating the coordinate downregulation of a panel of miRNAs. In turn, the miRNAs manifest growth suppressive effects and control cell proliferation in response to E2. This sheds a

  14. Induction of cell proliferation and survival genes by estradiol-repressed microRNAs in breast cancer cells

    Directory of Open Access Journals (Sweden)

    Yu Xinfeng

    2012-01-01

    Full Text Available Abstract Background In estrogen responsive MCF-7 cells, estradiol (E2 binding to ERα leads to transcriptional regulation of genes involved in the control of cell proliferation and survival. MicroRNAs (miRNAs have emerged as key post-transcriptional regulators of gene expression. The aim of this study was to explore whether miRNAs were involved in hormonally regulated expression of estrogen responsive genes. Methods Western blot and QPCR were used to determine the expression of estrogen responsive genes and miRNAs respectively. Target gene expression regulated by miRNAs was validated by luciferase reporter assays and transfection of miRNA mimics or inhibitors. Cell proliferation was evaluated by MTS assay. Results E2 significantly induced bcl-2, cyclin D1 and survivin expression by suppressing the levels of a panel of miRNAs (miR-16, miR-143, miR-203 in MCF-7 cells. MiRNA transfection and luciferase assay confirmed that bcl-2 was regulated by miR-16 and miR-143, cyclinD1 was modulated by miR-16. Importantly, survivin was found to be targeted by miR-16, miR-143, miR-203. The regulatory effect of E2 can be either abrogated by anti-estrogen ICI 182, 780 and raloxifene pretreatment, or impaired by ERα siRNA, indicating the regulation is dependent on ERα. In order to investigate the functional significance of these miRNAs in estrogen responsive cells, miRNAs mimics were transfected into MCF-7 cells. It revealed that overexpression of these miRNAs significantly inhibited E2-induced cell proliferation. Further study of the expression of the miRNAs indicated that miR-16, miR-143 and miR-203 were highly expressed in triple positive breast cancer tissues, suggesting a potential tumor suppressing effect of these miRNAs in ER positive breast cancer. Conclusions These results demonstrate that E2 induces bcl-2, cyclin D1 and survivin by orchestrating the coordinate downregulation of a panel of miRNAs. In turn, the miRNAs manifest growth suppressive effects

  15. Characterization of global microRNA expression reveals oncogenic potential of miR-145 in metastatic colorectal cancer

    International Nuclear Information System (INIS)

    MicroRNAs (MiRNAs) are short non-coding RNAs that control protein expression through various mechanisms. Their altered expression has been shown to be associated with various cancers. The aim of this study was to profile miRNA expression in colorectal cancer (CRC) and to analyze the function of specific miRNAs in CRC cells. MirVana miRNA Bioarrays were used to determine the miRNA expression profile in eight CRC cell line models, 45 human CRC samples of different stages, and four matched normal colon tissue samples. SW620 CRC cells were stably transduced with miR-143 or miR-145 expression vectors and analyzed in vitro for cell proliferation, cell differentiation and anchorage-independent growth. Signalling pathways associated with differentially expressed miRNAs were identified using a gene set enrichment analysis. The expression analysis of clinical CRC samples identified 37 miRNAs that were differentially expressed between CRC and normal tissue. Furthermore, several of these miRNAs were associated with CRC tumor progression including loss of miR-133a and gain of miR-224. We identified 11 common miRNAs that were differentially expressed between normal colon and CRC in both the cell line models and clinical samples. In vitro functional studies indicated that miR-143 and miR-145 appear to function in opposing manners to either inhibit or augment cell proliferation in a metastatic CRC model. The pathways targeted by miR-143 and miR-145 showed no significant overlap. Furthermore, gene expression analysis of metastatic versus non-metastatic isogenic cell lines indicated that miR-145 targets involved in cell cycle and neuregulin pathways were significantly down-regulated in the metastatic context. MiRNAs showing altered expression at different stages of CRC could be targets for CRC therapies and be further developed as potential diagnostic and prognostic analytes. The identified biological processes and signalling pathways collectively targeted by co-expressed miRNAs in

  16. MicroRNA-92a as a potential biomarker in diagnosis of colorectal cancer: a systematic review and meta-analysis.

    Directory of Open Access Journals (Sweden)

    Xin Yang

    Full Text Available INTRODUCTION: Previous studies demonstrated that MicroRNA-92a (miR-92a was significantly differential expressed between colorectal cancer (CRC patients and control cohorts, which provide timely relevant evidence for miR-92a as a novel promising biomarker in the colorectal cancer patients. This meta-analysis aimed to evaluate potential diagnostic value of plasma miR-92a. METHODS: Relevant literatures were collected in PubMed, Embase, Chinese Biomedical Literature Database (CBM, Chinese National Knowledge Infrastructure (CNKI and Technology of Chongqing (VIP, and Wan Fang Data. Sensitivity, specificity and diagnostic odds ratio (DOR for miR-92a in the diagnosis of CRC were pooled using random effects models. Summary receiver operating characteristic (SROC curve analysis and the area under the curve (AUC were used to estimate the overall test performance. RESULTS: This Meta-analysis included six studies with a total of 521 CRC patients and 379 healthy controls. For miR-92a, the pooled sensitivity, specificity and DOR to predict CRC patients were 76% (95% confidence interval [CI]: 72%-79%, 64% (95% confidence interval [CI]: 59%-69% and 8.05 (95% CI: 3.50-18.56, respectively. In addition, the AUC of miR-92a in diagnosis CRC is 0.7720. CONCLUSIONS: MicroRNA-92a might be a novel potential biomarker in the diagnosis of colorectal cancer, and more studies are needed to highlight the theoretical strengths.

  17. Tissue microRNA-21 expression predicted recurrence and poor survival in patients with colorectal cancer – a meta-analysis

    OpenAIRE

    Chen Z.; Liu H; Jin W; Ding Z; Zheng S; Yu Y

    2016-01-01

    Zexin Chen,1 Hui Liu,2 Wen Jin,2 Zheyuan Ding,2 Shuangshuang Zheng,2 Yunxian Yu2 1Department of Clinical Epidemiology and Biostatistics, The Second Affiliated Hospital, School of Medicine, Zhejiang University, 2Department of Epidemiology & Health Statistics, School of Public Health, School of Medicine, Zhejiang University, Hangzhou, People’s Republic of ChinaObjective: MicroRNA-21 (miR-21) has been shown to play an important role in cancer prognosis. We performed a meta-analysis to ...

  18. MicroRNA-663a is downregulated in non-small cell lung cancer and inhibits proliferation and invasion by targeting JunD

    OpenAIRE

    Zhang, Yi; Xu, Xiaoman; Zhang, Meng; wang, xin; Bai, Xue; Li, Hui; KAN, LIANG; Zhou, Yong; Niu, Huiyan; He, Ping

    2016-01-01

    Background MicroRNA-663a expression is downregulated in several tumors. However, its functions and mechanisms in human non-small cell lung (NSCLC) cancer remain obscure. The present study aimed to identify the expression pattern, biological roles and potential mechanisms by which miR-663a dysregulation is associated with NSCLC. Methods We examined expression level of miR-663a in 62 cases of NSCLC tissues and 5 NSCLC cell lines by reverse transcription PCR. In vitro, gain-of-function and loss-...

  19. Circulating MicroRNAs as Easy-to-Measure Aging Biomarkers in Older Breast Cancer Patients: Correlation with Chronological Age but Not with Fitness/Frailty Status

    OpenAIRE

    Hatse, Sigrid; Brouwers, Barbara; Dalmasso, Bruna; Laenen, Annouschka; Kenis, Cindy; Schöffski, Patrick; Wildiers, Hans

    2014-01-01

    Circulating microRNAs (miRNAs) hold great promise as easily accessible biomarkers for diverse (patho)physiological processes, including aging. We have compared miRNA expression profiles in cell-free blood from older versus young breast cancer patients, in order to identify “aging miRNAs” that can be used in the future to monitor the impact of chemotherapy on the patient’s biological age. First, we assessed 175 miRNAs that may possibly be present in serum/plasma in an exploratory screening in ...

  20. TARGET Researchers Identify Mutations in SIX1/2 and microRNA Processing Genes in Favorable Histology Wilms Tumor | Office of Cancer Genomics

    Science.gov (United States)

    TARGET researchers molecularly characterized favorable histology Wilms tumor (FHWT), a pediatric renal cancer. Comprehensive genome and transcript analyses revealed single-nucleotide substitution/deletion mutations in microRNA processing genes (15% of FHWT patients) and Sine Oculis Homeobox Homolog 1/2 (SIX1/2) genes (7% of FHWT patients). SIX1/2 genes play a critical role in renal development and were not previously associated with FHWT, thus presenting a novel role for SIX1/2 pathway aberrations in this disease.

  1. Downregulation of microRNA-498 in colorectal cancers and its cellular effects

    International Nuclear Information System (INIS)

    miR-498 is a non-coding RNA located intergenically in 19q13.41. Due to its predicted targeting of several genes involved in control of cellular growth, we examined the expression of miR-498 in colon cancer cell lines and a large cohort of patients with colorectal adenocarcinoma. Two colon cancer cancer cell lines (SW480 and SW48) and one normal colonic epithelial cell line (FHC) were recruited. The expression of miR-498 was tested in these cell lines by using quantitative real-time polymerase chain reaction (qRT-PCR). Tissues from 80 patients with surgical resection of colorectum (60 adenocarcinomas and 20 non-neoplastic tissues) were tested for miR-498 expression by qRT-PCR. In addition, an exogenous miR-498 (mimic) was used to detect the miRNA's effects on cell proliferation and cell cycle events in SW480 using MTT calorimetric assay and flow cytometry respectively. The colon cancer cell lines showed reduced expression of miR-498 compared to a normal colonic epithelial cell line. Mimic driven over expression of miR-498 in the SW480 cell line resulted in reduced cell proliferation and increased proportions of G2-M phase cells. In tissues, miR-498 expression was too low to be detected in all colorectal adenocarcinoma compared to non-neoplastic tissues. This suggests that the down regulation of miR-498 in colorectal cancer tissues and the direct suppressive cellular effect noted in cancer cell lines implies that miR-498 has some direct or indirect role in the pathogenesis of colorectal adenocarcinomas. - Highlights: • miR-498 is a non-coding RNA located in 19q13.41. • Colon cancer cell lines showed reduced expression of miR-498. • Mimic driven over expression of miR-498 in colon cancer cells resulted in lower cell proliferation. • miR-498 expression was down regulated in all colorectal adenocarcinoma tissues

  2. Downregulation of microRNA-498 in colorectal cancers and its cellular effects

    Energy Technology Data Exchange (ETDEWEB)

    Gopalan, Vinod; Smith, Robert A.; Lam, Alfred K.-Y., E-mail: a.lam@griffith.edu.au

    2015-01-15

    miR-498 is a non-coding RNA located intergenically in 19q13.41. Due to its predicted targeting of several genes involved in control of cellular growth, we examined the expression of miR-498 in colon cancer cell lines and a large cohort of patients with colorectal adenocarcinoma. Two colon cancer cancer cell lines (SW480 and SW48) and one normal colonic epithelial cell line (FHC) were recruited. The expression of miR-498 was tested in these cell lines by using quantitative real-time polymerase chain reaction (qRT-PCR). Tissues from 80 patients with surgical resection of colorectum (60 adenocarcinomas and 20 non-neoplastic tissues) were tested for miR-498 expression by qRT-PCR. In addition, an exogenous miR-498 (mimic) was used to detect the miRNA's effects on cell proliferation and cell cycle events in SW480 using MTT calorimetric assay and flow cytometry respectively. The colon cancer cell lines showed reduced expression of miR-498 compared to a normal colonic epithelial cell line. Mimic driven over expression of miR-498 in the SW480 cell line resulted in reduced cell proliferation and increased proportions of G2-M phase cells. In tissues, miR-498 expression was too low to be detected in all colorectal adenocarcinoma compared to non-neoplastic tissues. This suggests that the down regulation of miR-498 in colorectal cancer tissues and the direct suppressive cellular effect noted in cancer cell lines implies that miR-498 has some direct or indirect role in the pathogenesis of colorectal adenocarcinomas. - Highlights: • miR-498 is a non-coding RNA located in 19q13.41. • Colon cancer cell lines showed reduced expression of miR-498. • Mimic driven over expression of miR-498 in colon cancer cells resulted in lower cell proliferation. • miR-498 expression was down regulated in all colorectal adenocarcinoma tissues.

  3. Identification of differentially expressed microRNAs in epithelial ovarian cancer%卵巢上皮癌差异表达microRNAs的筛选研究

    Institute of Scientific and Technical Information of China (English)

    雷磊; 王艳丽; 梁静; 赵西侠; 王国庆

    2013-01-01

    Objective: Identifying the differentially expressed microRNAs in epithelial ovarian cancer compared with the adjacent tissues using microarray chip technology, and study the molecular mechanism in the development and progress of epithelial ovarian cancer. Methods: Eight pairs of epithelial ovarian cancer and adjacent normal tissues were obtained from patients undergoing surgery from June 2010 to June 2011 in the Center of women's tumors of Shaanxi Tumor Hospital. Total RNA was extracted and microRNAs microarray chip was used to screen the differentially expressed microRNAs. Real - time quantitative PCR was used to verify the microarray chip results. Then tumor - related genes targeted by the microRNAs were predicted by the microRNAs database. Results:Four microRNAs,miR -146a,miR -200c,miR -221 and miR -429 were significantly up - regulated and miR - 34b was significantly down - regulated combining the results of microarray chip and real - time quantitative PCR. Several tumor - related target genes were searched by the prediction database. Conclusion: Characterizing the differentially expressed microRNAs and target genes in epithelial ovarian cancer may provide a potential role for the carcinogenesis of epithelial ovarian cancer.%目的:利用microRNA微阵列芯片技术筛选卵巢上皮癌及癌旁组织中差异表达的microRNAs,发现与卵巢上皮癌相关的microRNAs,为进一步阐明卵巢上皮癌发生发展的分子机制提出依据.方法:选取2010年6月至2011年6月在陕西省肿瘤医院妇瘤中心行手术治疗的8例卵巢上皮癌及对应癌旁组织,提取组织总RNA,采用microRNA芯片杂交技术检测卵巢上皮癌及对应癌旁组织中microRNAs表达水平,经统计分析寻找可能的差异表达的microRNAs,应用实时定量PCR方法验证芯片结果.利用microRNA靶基因预测数据库检索得到差异表达microRNAs与肿瘤相关的靶基因.结果:结合芯片与实时定量PCR结果,筛选获得miR-146a、miR-200c

  4. Robustness and backbone motif of a cancer network regulated by miR-17-92 cluster during the G1/S transition.

    Directory of Open Access Journals (Sweden)

    Lijian Yang

    Full Text Available Based on interactions among transcription factors, oncogenes, tumor suppressors and microRNAs, a Boolean model of cancer network regulated by miR-17-92 cluster is constructed, and the network is associated with the control of G1/S transition in the mammalian cell cycle. The robustness properties of this regulatory network are investigated by virtue of the Boolean network theory. It is found that, during G1/S transition in the cell cycle process, the regulatory networks are robustly constructed, and the robustness property is largely preserved with respect to small perturbations to the network. By using the unique process-based approach, the structure of this network is analyzed. It is shown that the network can be decomposed into a backbone motif which provides the main biological functions, and a remaining motif which makes the regulatory system more stable. The critical role of miR-17-92 in suppressing the G1/S cell cycle checkpoint and increasing the uncontrolled proliferation of the cancer cells by targeting a genetic network of interacting proteins is displayed with our model.

  5. Tumor suppressive microRNA-218 inhibits cancer cell migration and invasion through targeting laminin-332 in head and neck squamous cell carcinoma.

    Science.gov (United States)

    Kinoshita, Takashi; Hanazawa, Toyoyuki; Nohata, Nijiro; Kikkawa, Naoko; Enokida, Hideki; Yoshino, Hirofumi; Yamasaki, Takeshi; Hidaka, Hideo; Nakagawa, Masayuki; Okamoto, Yoshitaka; Seki, Naohiko

    2012-11-01

    Recent our microRNA (miRNA) expression signature revealed that expression of microRNA-218 (miR-218) was reduced in cancer tissues, suggesting a candidate of tumor suppressor in head and neck squamous cell carcinoma (HNSCC). The aim of this study was to investigate the functional significance of miR-218 and its mediated moleculer pathways in HNSCC. Restoration of miR-218 in cancer cells led to significant inhibition of cell migration and invasion activities in HNSCC cell lines (FaDu and SAS). Genome-wide gene expression analysis of miR-218 transfectants and in silico database analysis showed that focal adhesion pathway was a promising candidate of miR-218 target pathways. The laminins are an important and biologically active part of the basal lamina, the function of that are various such as influencing cell differentiation, migration and adhesion as well as proliferation and cell survival. Interestingly, all components of laminin-332 (LAMA3, LAMB3 and LAMC2) are listed on the candidate genes in focal adhesion pathway. Furthermore, we focused on LAMB3 which has a miR-218 target site and gene expression studies and luciferase reporter assays showed that LAMB3 was directly regulated by miR-218. Silencing study of LAMB3 demonstrated significant inhibition of cell migration and invasion. In clinical specimens with HNSCC, the expression levels of laminin-332 were significantly upregulated in cancer tissues compared to adjacent non-cancerous tissues. Our analysis data showed that tumor suppressive miR-218 contributes to cancer cell migration and invasion through regulating focal adhesion pathway, especially laminin-332. Tumor suppressive miRNA-mediated novel cancer pathways provide new insights into the potential mechanisms of HNSCC oncogenesis. PMID:23159910

  6. Identification of a microRNA signature in dendritic cell vaccines for cancer immunotherapy

    DEFF Research Database (Denmark)

    Holmstrøm, Kim; Pedersen, Ayako Wakatsuki; Claesson, Mogens Helweg;

    2010-01-01

    Dendritic cells (DCs) exposed to tumor antigens followed by treatment with T(h)1-polarizing differentiation signals have paved the way for the development of DC-based cancer vaccines. Critical parameters for assessment of the optimal functional state of DCs and prediction of the vaccine potency of...

  7. Changes of microRNA profile and microRNA-mRNA regulatory network in bones of ovariectomized mice.

    Science.gov (United States)

    An, Jee Hyun; Ohn, Jung Hun; Song, Jung Ah; Yang, Jae-Yeon; Park, Hyojung; Choi, Hyung Jin; Kim, Sang Wan; Kim, Seong Yeon; Park, Woog-Yang; Shin, Chan Soo

    2014-03-01

    Growing evidence shows the possibility of a role of microRNAs (miRNA) in regulating bone mass. We investigated the change of miRNAs and mRNA expression profiles in bone tissue in an ovariectomized mice model and evaluated the regulatory mechanism of bone mass mediated by miRNAs in an estrogen-deficiency state. Eight-week-old female C3H/HeJ mice underwent ovariectomy (OVX) or sham operation (Sham-op), and their femur and tibia were harvested to extract total bone RNAs after 4 weeks for microarray analysis. Eight miRNAs (miR-127, -133a, -133a*, -133b, -136, -206, -378, -378*) were identified to be upregulated after OVX, whereas one miRNA (miR-204) was downregulated. Concomitant analysis of mRNA microarray revealed that 658 genes were differentially expressed between OVX and Sham-op mice. Target prediction of differentially expressed miRNAs identified potential targets, and integrative analysis using the mRNA microarray results showed that PPARγ and CREB pathways are activated in skeletal tissues after ovariectomy. Among the potential candidates of miRNA, we further studied the role of miR-127 in vitro, which exhibited the greatest changes after OVX. We also studied the effects of miR-136, which has not been studied in the context of bone mass regulation. Transfection of miR-127 inhibitor has enhanced osteoblastic differentiation in UAMS-32 cells as measured by alkaline phosphatase activities and mRNA expression of osteoblast-specific genes, whereas miR-136 precursor has inhibited osteoblastic differentiation. Furthermore, transfection of both miR-127 and miR-136 inhibitors enhanced the osteocyte-like morphological changes and survival in MLO-Y4 cells, whereas precursors of miR-127 and -136 have aggravated dexamethasone-induced cell death. Both of the precursors enhanced osteoclastic differentiation in bone marrow macrophages, indicating that both miR-127 and -136 are negatively regulating bone mass. Taken together, these results suggest a novel insight into the

  8. Attenuation of the beta-catenin/TCF4 complex in colorectal cancer cells induces several growth-suppressive microRNAs that target cancer promoting genes

    DEFF Research Database (Denmark)

    Schepeler, Troels; Holm, Anja; Halvey, P; Nordentoft, Iver Kristiansen; Lamy, Philippe; Riising, Eva Madi; Christensen, Lise Lotte; Thorsen, Kasper; Liebler, D C; Helin, Kristian; Ørntoft, Torben Falck; Andersen, Claus Lindbjerg

    2012-01-01

    MicroRNA Cards, capable of detecting 664 unique human microRNAs (miRNAs), to describe changes of the miRNA transcriptome following disruption of beta-catenin/TCF4 activity in DLD1 CRC cells. Most miRNAs appeared to respond independent of host gene regulation and proximal TCF4 chromatin occupancy as...

  9. Human Ribosomal RNA-Derived Resident MicroRNAs as the Transmitter of Information upon the Cytoplasmic Cancer Stress

    Science.gov (United States)

    2016-01-01

    Dysfunction of ribosome biogenesis induces divergent ribosome-related diseases including ribosomopathy and occasionally results in carcinogenesis. Although many defects in ribosome-related genes have been investigated, little is known about contribution of ribosomal RNA (rRNA) in ribosome-related disorders. Meanwhile, microRNA (miRNA), an important regulator of gene expression, is derived from both coding and noncoding region of the genome and is implicated in various diseases. Therefore, we performed in silico analyses using M-fold, TargetScan, GeneCoDia3, and so forth to investigate RNA relationships between rRNA and miRNA against cellular stresses. We have previously shown that miRNA synergism is significantly correlated with disease and the miRNA package is implicated in memory for diseases; therefore, quantum Dynamic Nexus Score (DNS) was also calculated using MESer program. As a result, seventeen RNA sequences identical with known miRNAs were detected in the human rRNA and termed as rRNA-hosted miRNA analogs (rmiRNAs). Eleven of them were predicted to form stem-loop structures as pre-miRNAs, and especially one stem-loop was completely identical with hsa-pre-miR-3678 located in the non-rDNA region. Thus, these rmiRNAs showed significantly high DNS values, participation in regulation of cancer-related pathways, and interaction with nucleolar RNAs, suggesting that rmiRNAs may be stress-responsible resident miRNAs which transmit stress-tuning information in multiple levels.

  10. microRNA-145 Mediates the Inhibitory Effect of Adipose Tissue-Derived Stromal Cells on Prostate Cancer.

    Science.gov (United States)

    Takahara, Kiyoshi; Ii, Masaaki; Inamoto, Teruo; Nakagawa, Takatoshi; Ibuki, Naokazu; Yoshikawa, Yuki; Tsujino, Takuya; Uchimoto, Taizo; Saito, Kenkichi; Takai, Tomoaki; Tanda, Naoki; Minami, Koichiro; Uehara, Hirofumi; Komura, Kazumasa; Hirano, Hajime; Nomi, Hayahito; Kiyama, Satoshi; Asahi, Michio; Azuma, Haruhito

    2016-09-01

    Adipose-derived stromal cell (ASC), known as one of the mesenchymal stem cells (MSCs), is a promising tool for regenerative medicine; however, the effect of ASCs on tumor growth has not been studied sufficiently. We investigated the hypothesis that ASCs have an inhibitory effect on metastatic tumor progression. To evaluate the in vitro inhibitory effect of ASCs on metastatic prostate cancer (PCa), direct coculture and indirect separate culture experiments with PC3M-luc2 cells and human ASCs were performed, and ASCs were administered to PC3M-luc2 cell-derived tumor-bearing nude mice for in vivo experiment. We also performed exosome microRNA (miRNA) array analysis to explore a mechanistic insight into the effect of ASCs on PCa cell proliferation/apoptosis. Both in vitro and in vivo experiments exhibited the inhibitory effect of ASCs on PC3M-luc2 cell proliferation, inducing apoptosis and PCa growth, respectively. Among upregulated miRNAs in ASCs compared with fibroblasts, we focused on miR-145, which was known as a tumor suppressor. ASC-derived conditioned medium (CM) significantly inhibited PC3M-luc2 cell proliferation, inducing apoptosis, but the effect was canceled by miR-145 knockdown in ASCs. ASC miR-145 knockdown CM also reduced the expression of Caspase 3/7 with increased antiapoptotic protein, BclxL, expression in PC3M-luc2 cells. This study provides preclinical data that ASCs inhibit PCa growth, inducing PCa cell apoptosis with reduced activity of BclxL, at least in part, by miR-145, including exosomes released from ASCs, suggesting that ASC administration could be a novel and promising therapeutic strategy in patients with PCa. PMID:27465939

  11. MicroRNA-9 suppresses cell migration and invasion through downregulation of TM4SF1 in colorectal cancer.

    Science.gov (United States)

    Park, Young Ran; Lee, Soo Teik; Kim, Se Lim; Liu, Yu Chuan; Lee, Min Ro; Shin, Ja Hyun; Seo, Seung Young; Kim, Seong Hun; Kim, In Hee; Lee, Seung Ok; Kim, Sang Wook

    2016-05-01

    Transmembrane-4-L6 family 1 (TM4SF1) is upregulated in colorectal carcinoma (CRC). However, the mechanism leading to inhibition of the TM4SF1 is not known. In the present study, we investigated the regulation of TM4SF1 and function of microRNAs (miRNAs) in CRC invasion and metastasis. We analyzed 60 colon cancers and paired normal specimens for TM4SF1 and miRNA-9 (miR-9) expression using quantitative real-time PCR. A bioinformatics analysis identified a putative miR-9 binding site within the 3'-UTR of TM4SF1. We also found that TM4SF1 was upregulated in CRC tissues and CRC cell lines. The expression of TM4SF1 was positively correlated with clinical advanced stage and lymph node metastasis. Moreover, a luciferase assay revealed that miR-9 directly targeted 3'-UTR-TM4SF1. Overexpression of miR-9 inhibited expression of TM4SF1 mRNA and protein, wound healing, transwell migration and invasion of SW480 cells, whereas, overexpression of anti-miR-9 and siRNA-TM4SF1 inversely regulated the TM4SF1 mRNA and protein level in HCT116 cells. Furthermore, miR-9 suppressed not only TM4SF1 expression but also MMP-2, MMP-9 and VEGF expression. In clinical specimens, miR-9 was generally down-regulated in CRC and inversely correlated with TM4SF1 expression. These results suggest that miR-9 functions as a tumor-suppressor in CRC, and that its suppressive effects mediate invasion and metastasis by inhibition of TM4SF1 expression. Our results also indicate that miR-9 might be a novel target for the treatment of CRC invasion and metastasis. PMID:26983891

  12. Relation between Ku80 and microRNA-99a expression and late rectal bleeding after radiotherapy for prostate cancer

    International Nuclear Information System (INIS)

    Background and purpose: Late rectal bleeding is one of the severe adverse events after radiotherapy for prostate cancer. New biomarkers are needed to allow a personalized treatment. Materials and methods: Four patients each with grade 0–1 or grade 2–3 rectal bleeding were randomly selected for miRNA array to examine miRNA expression in peripheral blood lymphocytes (PBLs). Based on results of miRNA array, 1 of 348 miRNAs was selected for microRNA assays. Then, expression of DNA-dependent protein kinase mRNA and miR-99a was analyzed in the PBLs of 97 patients. PBLs were exposed to 4 Gy of X-ray ex-vivo. Results: In the discovery cohort, grade 2–3 rectal bleeding was significantly higher in the Ku80 <1.09 expression group compared with ⩾1.09 group (P = 0.011). In radiation-induced expression of miR-99a, grade 2–3 rectal bleeding was significantly higher in the miR-99a IR(+)/IR(−) >0.93 group compared with ⩽0.93 group (P = 0.013). Most patients with grade 2–3 rectal bleeding were in the group with low Ku80 and high miR-99a expression. In the validation cohort, similar results were obtained. Conclusion: A combination of low Ku80 expression and highly-induced miR-99a expression could be a promising marker for predicting rectal bleeding after radiotherapy

  13. Integrative analysis of microRNA and mRNA expression profiles in non-small-cell lung cancer.

    Science.gov (United States)

    Yang, C; Sun, C; Liang, X; Xie, S; Huang, J; Li, D

    2016-04-01

    Non-small-cell lung cancer (NSCLC) represents the most common deadly disease. Emerging evidences suggest that abnormal epigenetic modulation via mRNAs and microRNAs (miRNAs) might be involved in the tumorigenesis. To explore novel therapeutic target of NSCLC, a more detailed mRNAs and miRNA expression profiling study is needed. High-quality total RNA including miRNA was isolated from NSCLC tissue and para-carcinoma tissue and used for RNA and small RNA sequencing. Results were analyzed bioinformatically and validated using quantitative real-time (qRT)-PCR. A total of 3530 genes (1977 up-regulated and 1553 down-regulated) and 211 miRNAs (171 up-regulated and 30 down-regulated) were differentially expressed (DE) in NSCLC tissue versus adjacent normal tissues. Furthermore, 157 novel miRNAs were predicted in our samples. Of these, 918 significant miRNA-mRNA pairs were identified, consisting of 100 miRNAs and 443 mRNAs. Gene ontology analysis revealed that most of the target genes were enriched in the terms of plasma membrane, binding, and multiple biological-molecular signaling processes. Pathway analysis of these miRNA signatures highlights their critical roles in calcium signaling pathway. Using qRT-PCR, the expression of several DE genes (KRAS and RBM5) and miRNAs (miR-1-5p, let-7b-5p, miR-21-5p, miR-1290, miR-149-5p, chr8_28846, chrX_31594, and chr9_29897) were confirmed. The integrative analysis based on mRNA and miRNA profiling may provide more potential molecular for the tumorigenesis and development of NSCLC. PMID:26964645

  14. MicroRNA expression profiling in bladder cancer: the challenge of next-generation sequencing in tissues and biofluids.

    Science.gov (United States)

    Matullo, Giuseppe; Naccarati, Alessio; Pardini, Barbara

    2016-05-15

    Bladder cancer (BC) is a heterogeneous disease characterized by a high recurrence rate that necessitates continuous cystoscopic surveillance. MicroRNAs (miRNAs) are detectable in tissues and biofluids such as plasma/serum and urine. They represent promising biomarkers with potential not only for detecting BC but also informing on prognosis and monitoring treatment response. In this review, the many aspects of the application of next-generation sequencing (NGS) to evaluate miRNA expression in BC is discussed, including technical issues as well as a comparison with results obtained by qRT-PCR. The available studies investigating miRNA profiling in BC by NGS are described, with particular attention to the potential applicability on biofluids. Altered miRNA levels have been observed in BC tissues by NGS, but these results so far only partially overlapped among studies and with previous data obtained by qRT-PCR. The discrepancies can be ascribed to the small groups of BC patients sequenced. The few available studies on biofluids are mainly focused on implementing RNA isolation and sequencing workflow. Using NGS to analyze miRNAs in biofluids can potentially provide results comparable to tissues with no invasive procedures for the patients. In particular, the analyses performed on exosomes/microvesicles appear to be more informative. Thanks to the improvement of both wet-lab procedures and pipelines/tools for data analyses, NGS studies on biofluids will be performed on a larger scale. MiRNAs detected in urine and serum/plasma will demonstrate their potentiality to describe the variegated scenario of BC and to become relevant clinical markers. PMID:26489968

  15. Human Ribosomal RNA-Derived Resident MicroRNAs as the Transmitter of Information upon the Cytoplasmic Cancer Stress.

    Science.gov (United States)

    Yoshikawa, Masaru; Fujii, Yoichi Robertus

    2016-01-01

    Dysfunction of ribosome biogenesis induces divergent ribosome-related diseases including ribosomopathy and occasionally results in carcinogenesis. Although many defects in ribosome-related genes have been investigated, little is known about contribution of ribosomal RNA (rRNA) in ribosome-related disorders. Meanwhile, microRNA (miRNA), an important regulator of gene expression, is derived from both coding and noncoding region of the genome and is implicated in various diseases. Therefore, we performed in silico analyses using M-fold, TargetScan, GeneCoDia3, and so forth to investigate RNA relationships between rRNA and miRNA against cellular stresses. We have previously shown that miRNA synergism is significantly correlated with disease and the miRNA package is implicated in memory for diseases; therefore, quantum Dynamic Nexus Score (DNS) was also calculated using MESer program. As a result, seventeen RNA sequences identical with known miRNAs were detected in the human rRNA and termed as rRNA-hosted miRNA analogs (rmiRNAs). Eleven of them were predicted to form stem-loop structures as pre-miRNAs, and especially one stem-loop was completely identical with hsa-pre-miR-3678 located in the non-rDNA region. Thus, these rmiRNAs showed significantly high DNS values, participation in regulation of cancer-related pathways, and interaction with nucleolar RNAs, suggesting that rmiRNAs may be stress-responsible resident miRNAs which transmit stress-tuning information in multiple levels. PMID:27517048

  16. The rectal cancer microRNAome - microRNA expression in rectal cancer and matched normal mucosa

    DEFF Research Database (Denmark)

    Gaedcke, Jochen; Grade, Marian; Camps, Jordi;

    2012-01-01

    PURPOSE: miRNAs play a prominent role in a variety of physiologic and pathologic biologic processes, including cancer. For rectal cancers, only limited data are available on miRNA expression profiles, whereas the underlying genomic and transcriptomic aberrations have been firmly established. We...... therefore, aimed to comprehensively map the miRNA expression patterns of this disease. EXPERIMENTAL DESIGN: Tumor biopsies and corresponding matched mucosa samples were prospectively collected from 57 patients with locally advanced rectal cancers. Total RNA was extracted, and tumor and mucosa mi......RNA expression profiles were subsequently established for all patients. The expression of selected miRNAs was validated using semi-quantitative real-time PCR. RESULTS: Forty-nine miRNAs were significantly differentially expressed (log(2)-fold difference >0.5 and P < 0.001) between rectal cancer and normal rectal...

  17. Combination of microRNA expression profiling with genome-wide SNP genotyping to construct a coronary artery disease-related miRNA-miRNA synergistic network.

    Science.gov (United States)

    Hua, Lin; Xia, Hong; Zhou, Ping; Li, Dongguo; Li, Lin

    2014-12-01

    In recent years, microRNAs (miRNAs) were found to play critical roles in many important biological processes. On the other hand, the rapid development of genome-wide association studies (GWAS) help identify potential genetic variants associated with the disease phenotypic variance. Therefore, we suggested a combined analysis of microRNA expression profiling with genome-wide Single Nucleotide Polymorphism (SNP) genotyping to identify potential disease-related biomarkers. Considering functional SNPs in miRNA genes or target sites might be important signals associated with human complex diseases, we constructed a miRNA-miRNA synergistic network related to coronary artery disease (CAD) by performing a genome-wide scan for SNPs in human miRNA 3' -untranslated regions (UTRs) target sites and computed potential SNP cooperation effects contributing to disease based on potential miRNA-SNP interactions reported recently. Furthermore, we identified some potential CAD-related miRNAs by analyzing the constructed miRNAmiRNA synergistic network. As a result, the predicted miRNA-miRNA network and miRNA clusters were validated by significantly high interaction effects of CAD-related miRNAs. Accurate classification performances were obtained for all of the identified miRNA clusters, and the sensitivity and specificity were all more than 90%. The network topological analysis confirmed some novel CAD-related miRNAs identified recently by experiments. Our method might help to understand miRNA function and CAD disease, as well as to explore the novel mechanisms involved. PMID:25641175

  18. Common genetic polymorphisms of microRNA biogenesis pathway genes and breast cancer survival

    Directory of Open Access Journals (Sweden)

    Sung Hyuna

    2012-05-01

    Full Text Available Abstract Background Although the role of microRNA’s (miRNA’s biogenesis pathway genes in cancer development and progression has been well established, the association between genetic variants of this pathway genes and breast cancer survival is still unknown. Methods We used genotype data available from a previously conducted case–control study to investigate association between common genetic variations in miRNA biogenesis pathway genes and breast cancer survival. We investigated the possible associations between 41 germ-line single-nucleotide polymorphisms (SNPs and both disease free survival (DFS and overall survival (OS among 488 breast cancer patients. During the median follow-up of 6.24 years, 90 cases developed disease progression and 48 cases died. Results Seven SNPs were significantly associated with breast cancer survival. Two SNPs in AGO2 (rs11786030 and rs2292779 and DICER1 rs1057035 were associated with both DFS and OS. Two SNPs in HIWI (rs4759659 and rs11060845 and DGCR8 rs9606250 were associated with DFS, while DROSHA rs874332 and GEMIN4 rs4968104 were associated with only OS. The most significant association was observed in variant allele of AGO2 rs11786030 with 2.62-fold increased risk of disease progression (95% confidence interval (CI, 1.41-4.88 and in minor allele homozygote of AGO2 rs2292779 with 2.94-fold increased risk of death (95% CI, 1.52-5.69. We also found cumulative effects of SNPs on DFS and OS. Compared to the subjects carrying 0 to 2 high-risk genotypes, those carrying 3 or 4–6 high-risk genotypes had an increased risk of disease progression with a hazard ratio of 2.16 (95% CI, 1.18- 3.93 and 4.47 (95% CI, 2.45- 8.14, respectively (P for trend, 6.11E-07. Conclusions Our results suggest that genetic variants in miRNA biogenesis pathway genes may be associated with breast cancer survival. Further studies in larger sample size and functional characterizations are warranted to validate these results.

  19. Common genetic polymorphisms of microRNA biogenesis pathway genes and breast cancer survival

    International Nuclear Information System (INIS)

    Although the role of microRNA’s (miRNA’s) biogenesis pathway genes in cancer development and progression has been well established, the association between genetic variants of this pathway genes and breast cancer survival is still unknown. We used genotype data available from a previously conducted case–control study to investigate association between common genetic variations in miRNA biogenesis pathway genes and breast cancer survival. We investigated the possible associations between 41 germ-line single-nucleotide polymorphisms (SNPs) and both disease free survival (DFS) and overall survival (OS) among 488 breast cancer patients. During the median follow-up of 6.24 years, 90 cases developed disease progression and 48 cases died. Seven SNPs were significantly associated with breast cancer survival. Two SNPs in AGO2 (rs11786030 and rs2292779) and DICER1 rs1057035 were associated with both DFS and OS. Two SNPs in HIWI (rs4759659 and rs11060845) and DGCR8 rs9606250 were associated with DFS, while DROSHA rs874332 and GEMIN4 rs4968104 were associated with only OS. The most significant association was observed in variant allele of AGO2 rs11786030 with 2.62-fold increased risk of disease progression (95% confidence interval (CI), 1.41-4.88) and in minor allele homozygote of AGO2 rs2292779 with 2.94-fold increased risk of death (95% CI, 1.52-5.69). We also found cumulative effects of SNPs on DFS and OS. Compared to the subjects carrying 0 to 2 high-risk genotypes, those carrying 3 or 4–6 high-risk genotypes had an increased risk of disease progression with a hazard ratio of 2.16 (95% CI, 1.18- 3.93) and 4.47 (95% CI, 2.45- 8.14), respectively (P for trend, 6.11E-07). Our results suggest that genetic variants in miRNA biogenesis pathway genes may be associated with breast cancer survival. Further studies in larger sample size and functional characterizations are warranted to validate these results

  20. Radiology Network (ACRIN) - Cancer Imaging Program

    Science.gov (United States)

    ACRIN is funded to improve the quality and utility of imaging in cancer research and cancer care through expert, multi-institutional clinical evaluation of discoveries and technological innovations relevant to imaging science as applied in clinical oncology.

  1. International network of cancer genome projects.

    OpenAIRE

    Aretz, Axel; Bernabé, Rosa R.; Eerola, Iiro; Hemsley, Fiona M.; Jennings, Jennifer L.; Kerr, David; Klatt, Peter; Kolar, Patrik; Lane, David P; Laplace, Frank; Nettekoven, Gerd; Remacle, Jacques; WATANABE, Koichi; Yuen, Matthew M. F.; Knoppers, Bartha M.

    2010-01-01

    The International Cancer Genome Consortium (ICGC) was launched to coordinate large-scale cancer genome studies in tumours from 50 different cancer types and/or subtypes that are of clinical and societal importance across the globe. Systematic studies of more than 25,000 cancer genomes at the genomic, epigenomic and transcriptomic levels will reveal the repertoire of oncogenic mutations, uncover traces of the mutagenic influences, define clinically relevant subtypes for prognosis and therapeut...

  2. Global microRNA analysis of the NCI-60 cancer cell panel

    DEFF Research Database (Denmark)

    Søkilde, Rolf; Kaczkowski, Bogumil; Podolska, Agnieszka;

    2011-01-01

    progression of cancer, they comprise a novel class of promising diagnostic and prognostic molecular markers and potential drug targets. By applying an LNA-enhanced microarray platform, we studied the expression profiles of 955 miRNAs in the NCI-60 cancer cell lines and identified tissue- and cell...... contributes expression data for 369 miRNAs that have not previously been profiled. Finally, by matching drug sensitivity data for the NCI-60 cells to their miRNA expression profiles, we found numerous drug-miRNAs pairs, for which the miRNA expression and drug sensitivity profiles were highly correlated and...... thus represent potential candidates for further investigation of drug resistance and sensitivity mechanisms....

  3. Overexpression of the lung cancer-prognostic miR-146b microRNAs has a minimal and negative effect on the malignant phenotype of A549 lung cancer cells.

    Directory of Open Access Journals (Sweden)

    Santosh Kumar Patnaik

    Full Text Available INTRODUCTION: Expression levels of miR-146b-5p and -3p microRNAs in human non-small cell lung cancer (NSCLC are associated with recurrence of the disease after surgery. To understand this, the effect of miR-146b overexpression was studied in A549 human lung cancer cells. METHODS: A549 cells, engineered with lentiviruses to overexpress the human pre-miR-146b precursor microRNA, were examined for proliferation, colony formation on plastic surface and in soft agar, migration and invasiveness in cell culture and in vivo in mice, chemosensitivity to cisplatin and doxorubicin, and global gene expression. miR-146b expressions were assessed in microdissected stroma and epithelia of human NSCLC tumors. Association of miR-146b-5p and -3p expression in early stage NSCLC with recurrence was analyzed. PRINCIPAL FINDINGS: A549 pre-miR-146b-overexpressors had 3-8-fold higher levels of both miR-146b microRNAs than control cells. Overexpression did not alter cellular proliferation, chemosensitivity, migration, or invasiveness; affected only 0.3% of the mRNA transcriptome; and, reduced the ability to form colonies in vitro by 25%. In human NSCLC tumors, expression of both miR-146b microRNAs was 7-10-fold higher in stroma than in cancerous epithelia, and higher miR-146b-5p but lower -3p levels were predictive of recurrence. CONCLUSIONS: Only a minimal effect of pre-miR-146b overexpression on the malignant phenotype was seen in A549 cells. This could be because of opposing effects of miR-146b-5p and -3p overexpression as suggested by the conflicting recurrence-predictive values of the two microRNAs, or because miR-146b expression changes in non-cancerous stroma and not cancerous epithelia of tumors are responsible for the prognostic value of miR-146b.

  4. MicroRNAs Linked to Trastuzumab Resistance, Brain Metastases | Division of Cancer Prevention

    Science.gov (United States)

    Researchers have tied increased levels of a microRNA (miRNA) to resistance to the targeted therapy trastuzumab (Herceptin) in women with HER2-positive breast cancer. Another research team has discovered a “signature” of miRNAs in brain metastases in patients with melanoma—a signature that is also present in the primary tumor and could identify melanoma patients at increased risk of brain metastases. |

  5. Families of microRNAs Expressed in Clusters Regulate Cell Signaling in Cervical Cancer

    Directory of Open Access Journals (Sweden)

    Luis Steven Servín-González

    2015-06-01

    Full Text Available Tumor cells have developed advantages to acquire hallmarks of cancer like apoptosis resistance, increased proliferation, migration, and invasion through cell signaling pathway misregulation. The sequential activation of genes in a pathway is regulated by miRNAs. Loss or gain of miRNA expression could activate or repress a particular cell axis. It is well known that aberrant miRNA expression is well recognized as an important step in the development of cancer. Individual miRNA expression is reported without considering that miRNAs are grouped in clusters and may have similar functions, such as the case of clusters with anti-oncomiRs (23b~27b~24-1, miR-29a~29b-1, miR-29b-2~29c, miR-99a~125b-2, miR-99b~125a, miR-100~125b-1, miR-199a-2~214, and miR-302s or oncomiRs activity (miR-1-1~133a-2, miR-1-2~133a-1, miR-133b~206, miR-17~92, miR-106a~363, miR183~96~182, miR-181a-1~181b-1, and miR-181a-2~181b-2, which regulated mitogen-activated protein kinases (MAPK, phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K, NOTCH, proteasome-culling rings, and apoptosis cell signaling. In this work we point out the pathways regulated by families of miRNAs grouped in 20 clusters involved in cervical cancer. Reviewing how miRNA families expressed in cluster-regulated cell path signaling will increase the knowledge of cervical cancer progression, providing important information for therapeutic, diagnostic, and prognostic methodology design.

  6. Tumor suppressive microRNA-133a regulates novel targets: Moesin contributes to cancer cell proliferation and invasion in head and neck squamous cell carcinoma

    International Nuclear Information System (INIS)

    Highlights: ► Tumor suppressive microRNA-133a regulates moesin (MSN) expression in HNSCC. ► Silencing of MSN in HNSCC cells suppressed proliferation, migration and invasion. ► The expression level of MSN was significantly up-regulated in cancer tissues. -- Abstract: Recently, many studies suggest that microRNAs (miRNAs) contribute to the development, invasion and metastasis of various types of human cancers. Our recent study revealed that expression of microRNA-133a (miR-133a) was significantly reduced in head and neck squamous cell carcinoma (HNSCC) and that restoration of miR-133a inhibited cell proliferation, migration and invasion in HNSCC cell lines, suggesting that miR-133a function as a tumor suppressor. Genome-wide gene expression analysis of miR-133a transfectants and TargetScan database showed that moesin (MSN) was a promising candidate of miR-133a target gene. MSN is a member of the ERM (ezrin, radixin and moesin) protein family and ERM function as cross-linkers between plasma membrane and actin-based cytoskeleton. The functions of MSN in cancers are controversial in previous reports. In this study, we focused on MSN and investigated whether MSN was regulated by tumor suppressive miR-133a and contributed to HNSCC oncogenesis. Restoration of miR-133a in HNSCC cell lines (FaDu, HSC3, IMC-3 and SAS) suppressed the MSN expression both in mRNA and protein level. Silencing study of MSN in HNSCC cell lines demonstrated significant inhibitions of cell proliferation, migration and invasion activities in si-MSN transfectants. In clinical specimen with HNSCC, the expression level of MSN was significantly up-regulated in cancer tissues compared to adjacent non-cancerous tissues. These data suggest that MSN may function as oncogene and is regulated by tumor suppressive miR-133a. Our analysis data of novel tumor-suppressive miR-133a-mediated cancer pathways could provide new insights into the potential mechanisms of HNSCC oncogenesis.

  7. Downregulation of microRNA-206 promotes invasion and angiogenesis of triple negative breast cancer.

    Science.gov (United States)

    Liang, Zhongxing; Bian, Xuehai; Shim, Hyunsuk

    2016-08-26

    Triple negative breast tumors don't respond to Tamoxifen and Herceptin, two of the most effective medications for treating breast cancer. Additionally, triple negative breast cancer (TNBC) intrinsically resists or will eventually acquire resistance to chemotherapy. The purpose of this study is to understand better the molecular basis of TNBC as well as develop new therapeutic strategies against it. Here, we analyzed miRNA-206 expression levels in breast cancer cell lines and tissues. In addition, we investigated whether miR-206 mimics inhibited TNBC tumor invasion and angiogenesis. The results showed that miR-206 was downregulated in TNBC compared to non-TNBC cell lines and tissues. Additionally, the decreased levels of miR-206 were inversely consistent with expression levels of VEGF. Furthermore, the forced expression of miR-206 in the mimic-transfected TNBC cells downregulated VEGF, MAPK3, and SOX9 expression levels. The miR-206 mimics inhibited TNBC breast cell invasion and angiogenesis. These findings demonstrate for the first time the involvement of miRNA-206 in TNBC invasion and angiogenesis and suggest that miR-206 may be an efficient agent for therapy of TNBC. PMID:27318091

  8. Human papilloma virus, DNA methylation and microRNA expression in cervical cancer (Review).

    Science.gov (United States)

    Jiménez-Wences, Hilda; Peralta-Zaragoza, Oscar; Fernández-Tilapa, Gloria

    2014-06-01

    Cancer is a complex disease caused by genetic and epigenetic abnormalities that affect gene expression. The progression from precursor lesions to invasive cervical cancer is influenced by persistent human papilloma virus (HPV) infection, which induces changes in the host genome and epigenome. Epigenetic alterations, such as aberrant miRNA expression and changes in DNA methylation status, favor the expression of oncogenes and the silencing of tumor-suppressor genes. Given that some miRNA genes can be regulated through epigenetic mechanisms, it has been proposed that alterations in the methylation status of miRNA promoters could be the driving mechanism behind their aberrant expression in cervical cancer. For these reasons, we assessed the relationship among HPV infection, cellular DNA methylation and miRNA expression. We conclude that alterations in the methylation status of protein-coding genes and various miRNA genes are influenced by HPV infection, the viral genotype, the physical state of the viral DNA, and viral oncogenic risk. Furthermore, HPV induces deregulation of miRNA expression, particularly at loci near fragile sites. This deregulation occurs through the E6 and E7 proteins, which target miRNA transcription factors such as p53. PMID:24737381

  9. AB053. MicroRNA expression profile in penile cancer revealed by next-generation small RNA sequencing

    Science.gov (United States)

    Zhang, Li; Wei, Pengfei

    2016-01-01

    Objective Penile cancer (PeCa) is a relatively rare tumor entity but possesses higher morbidity and mortality rates especially in developing countries. To date, the concrete pathogenic signaling pathways and core machineries involved in tumorigenesis and progression of PeCa remain to be elucidated. Several studies suggested miRNAs, which modulate gene expression at posttranscriptional level, were frequently mis-regulated and aberrantly expressed in human cancers. However, the miRNA profile in human PeCa has not been reported before. Methods In this present study, the miRNA profile was obtained from 10 fresh penile cancerous tissues and matched adjacent non-cancerous tissues via next-generation sequencing. Results As a result, a total of 751 and 806 annotated miRNAs were identified in normal and cancerous penile tissues, respectively. Among which, 56 miRNAs with significantly different expression levels between paired tissues were identified. Subsequently, several annotated miRNAs were randomly and validated using quantitative real-time PCR. Compared with the previous publications regarding to the altered miRNAs expression in various cancers and especially genitourinary (prostate, bladder, kidney, testis) cancers, the most majority of deregulated miRNAs showed the similar expression pattern in penile cancer. Moreover, the bioinformatics analyses suggested that the putative target genes of differentially expressed miRNAs between cancerous and matched normal penile tissues were tightly associated with cell junction, proliferation, growth as well as genomic instability and so on, by modulating Wnt, MAPK, p53, PI3K-Akt, Notch and TGF-β signaling pathways, which were all well-established to participate in cancer initiation and progression. Conclusions Our work presents a global view of the differentially expressed miRNAs and potentially regulatory networks of their target genes for clarifying the pathogenic transformation of normal penis to PeCa, which research resource

  10. MicroRNA-196a promotes non-small cell lung cancer cell proliferation and invasion through targeting HOXA5

    International Nuclear Information System (INIS)

    MicroRNAs (miRNAs) are short, non-coding RNAs (~22 nt) that play important roles in the pathogenesis of human diseases by negatively regulating gene expression. Although miR-196a has been implicated in several other cancers, its role in non-small cell lung cancer (NSCLC) is unknown. The aim of the present study was to examine the expression pattern of miR-196a in NSCLC and its clinical significance, as well as its biological role in tumor progression. Expression of miR-196a was analyzed in 34 NSCLC tissues and five NSCLC cell lines by quantitative reverse-transcription polymerase chain reaction (qRT-PCR). The effect of DNA methylation on miR-196a expression was investigated by 5-aza-2-deoxy-cytidine treatment and bisulfite sequencing. The effect of miR-196a on proliferation was evaluated by MTT and colony formation assays, and cell migration and invasion were evaluated by transwell assays. Analysis of target protein expression was determined by western blotting. Luciferase reporter plasmids were constructed to confirm the action of miR-196a on downstream target genes, including HOXA5. Differences between the results were tested for significance using Student’s t-test (two-tailed). miR-196a was highly expressed both in NSCLC samples and cell lines compared with their corresponding normal counterparts, and the expression of miR-196a may be affected by DNA demethylation. Higher expression of miR-196a in NSCLC tissues was associated with a higher clinical stage, and also correlated with NSCLC lymph-node metastasis. In vitro functional assays demonstrated that modulation of miR-196a expression affected NSCLC cell proliferation, migration and invasion. Our analysis showed that miR-196a suppressed the expression of HOXA5 both at the mRNA and protein levels, and luciferase assays confirmed that miR-196a directly bound to the 3’untranslated region of HOXA5. Knockdown of HOXA5 expression in A549 cells using RNAi was shown to promote NSCLC cell proliferation, migration

  11. Overexpression of members of the microRNA-183 family is a risk factor for lung cancer: A case control study

    International Nuclear Information System (INIS)

    Lung cancer is the leading cause of cancer-related deaths worldwide. Early detection is considered critical for lung cancer treatment. MicroRNAs (miRNAs) have shown promise as diagnostic and prognostic indicators. This study was to identify specific miRNAs with diagnostic and prognostic value for patients with lung cancer, and to explore the correlation between expression profiles of miRNAs and patient survival. Gene expression of members of the miR-183 family (miR-96, miR-182, and miR-183) were examined in 70 paired samples from lung cancer patients (primary cancer and non-cancerous tissues and sera), as well as 44 serum samples from normal volunteers and lung cancer cell lines by quantitative real-time reverse transcription polymerase chain reaction (RT-qPCR). The correlation between the expression of miRNAs in tissues, sera, and patient overall survival were also examined by log-rank and Cox regression analysis. Expression levels of members of the miR-183 family in lung cancer tumor and sera were higher than that of their normal counterparts. The miR-96 expression in tumors was positively associated with its expression in sera. Log-rank and Cox regression analyses demonstrated that high expression of tumor and serum miRNAs of the miR-183 family were associated with overall poor survival in patients with lung cancer. Our results suggest that the expressions of miR-96, miR-182, and miR-183 in tumor and sera may be considered potential novel biomarkers for the diagnosis and prognosis of lung cancer

  12. Cancer signaling networks and their implications for personalized medicine

    DEFF Research Database (Denmark)

    Creixell, Pau

    of the articles that are part of this PhD thesis (part II). In part III, we illustrate with an article that has been submitted recently, how next-generation sequencing data and mass spectrometry data can be combined to uncover genome-specific signaling networks. In part IV, I describe the two computational......) based on the integration of these cues; this integration and consequently the cellular decisions taken by cancer cells are arguably very distinct from the decisions that would be expected from non-cancer cells. Since cellular signaling networks and its different states are the computational circuits......Amongst the unique features of cancer cells perhaps the most crucial one is the change in the cellular decision-making process. While both non-cancer and cancer cells are constantly integrating different external cues that reach them and computing cellular decisions (e.g. proliferation or apoptosis...

  13. A Comprehensive Nuclear Receptor Network for Breast Cancer Cells

    Directory of Open Access Journals (Sweden)

    Ralf Kittler

    2013-02-01

    Full Text Available In breast cancer, nuclear receptors (NRs play a prominent role in governing gene expression, have prognostic utility, and are therapeutic targets. We built a regulatory map for 24 NRs, six chromatin state markers, and 14 breast-cancer-associated transcription factors (TFs that are expressed in the breast cancer cell line MCF-7. The resulting network reveals a highly interconnected regulatory matrix where extensive crosstalk occurs among NRs and other breast -cancer-associated TFs. We show that large numbers of factors are coordinately bound to highly occupied target regions throughout the genome, and these regions are associated with active chromatin state and hormone-responsive gene expression. This network also provides a framework for stratifying and predicting patient outcomes, and we use it to show that the peroxisome proliferator-activated receptor delta binds to a set of genes also regulated by the retinoic acid receptors and whose expression is associated with poor prognosis in breast cancer.

  14. Clinical Impact of a Novel MicroRNA Chemo-Sensitivity Predictor in Gastrooesophageal Cancer

    Science.gov (United States)

    Winther, Mette; Knudsen, Steen; Dahlgaard, Jesper; Jensen, Thomas; Hansen, Anker; Jensen, Peter Buhl; Tramm, Trine; Alsner, Jan; Nordsmark, Marianne

    2016-01-01

    Background miRNAs might be potentially useful biomarkers for prediction of response to chemotherapeutic agents, radiotherapy and survival. The aim of this retrospective study was to validate miRNA response predictors in a cohort of patients with gastrooesophageal cancer in order to predict overall survival (OS) and disease-specific survival (DSS). Material and Methods The study population encompassed 53 patients treated with curative intend for loco-regional gastrooesophageal cancer. miRNA expression was quantified from pre-therapeutic and diagnostic, formalin-fixed, paraffin embedded tumour specimens using Affymetrix GeneChip miRNA 1.0 Array. Based on growth inhibition of the NCI60 panel in the presence of cisplatin, epirubicine and capecitabine, a miRNA based response predictor was developed. The Cox proportional hazards model was applied to assess the correlations of the response predictor with OS and DSS. Results A univariate analysis demonstrated a statistical significant improvement of OS for patients who had undergone surgical resection with prediction scores above the median prediction score (HR: 0.41 (95% CI: 0.17–0.96). Adjusting for surgery and stage, this predictor was identified to be independently associated with both OS (HR: 0.37 (95% CI: 0.16–0.87)) and DSS (HR: 0.32 (0.12–0.87)). Conclusion The miRNA profile predictive for sensitivity to cisplatin, epirubicine and capecitabine was shown to be independently associated with OS and DSS in patients with gastrooesophageal cancer. PMID:26885979

  15. An integrated genome-wide approach to discover deregulated microRNAs in non-small cell lung cancer: Clinical significance of miR-23b-3p deregulation.

    Science.gov (United States)

    Begum, Shahnaz; Hayashi, Masamichi; Ogawa, Takenori; Jabboure, Fayez J; Brait, Mariana; Izumchenko, Evgeny; Tabak, Sarit; Ahrendt, Steven A; Westra, William H; Koch, Wayne; Sidransky, David; Hoque, Mohammad O

    2015-01-01

    In spite of significant technical advances, genesis and progression of non-small cell lung cancer (NSCLC) remain poorly understood. We undertook an integrated genetic approach to discover novel microRNAs that were deregulated in NSCLCs. A total 119 primary NSCLCs with matched normal were analyzed for genome-wide copy number changes. We also tested a subset of matched samples by microRNA expression array, and integrated them to identify microRNAs positioned in allelic imbalance area. Our findings support that most of the identified deregulated microRNAs (miR-21, miR-23b, miR-31, miR-126, miR-150, and miR-205) were positioned in allelic imbalance areas. Among microRNAs tested in independent 114 NSCLCs, overexpression of miR-23b was revealed to be a significantly poor prognostic factor of recurrence free survival (HR = 2.40, P = 0.005, 95%CI: 1.32-4.29) and overall survival (HR = 2.35, P = 0.005, 95%CI: 1.30-4.19) in multivariable analysis. In addition, overexpression of miR-23b in H1838 cell line significantly increased cell proliferation, while inhibition of miR-23b in H1437 and H1944 cell lines significantly decreased cell doubling time. In summary, integration of genomic analysis and microRNA expression profiling could identify novel cancer-related microRNAs, and miR-23b could be a potential prognostic marker for early stage NSCLCs. Further biological studies of miR-23b are warranted for the potential development of targeted therapy. PMID:26314549

  16. Differential expression of miR-1, a putative tumor suppressing microRNA, in cancer resistant and cancer susceptible mice

    Directory of Open Access Journals (Sweden)

    Jessica L. Fleming

    2013-04-01

    Full Text Available Mus spretus mice are highly resistant to several types of cancer compared to Mus musculus mice. To determine whether differences in microRNA (miRNA expression account for some of the differences in observed skin cancer susceptibility between the strains, we performed miRNA expression profiling of skin RNA for over 300 miRNAs. Five miRNAs, miR-1, miR-124a-3, miR-133a, miR-134, miR-206, were differentially expressed by array and/or qPCR. miR-1 was previously shown to have tumor suppressing abilities in multiple tumor types. We found miR-1 expression to be lower in mouse cutaneous squamous cell carcinomas (cSCCs compared to normal skin. Based on the literature and our expression data, we performed detailed studies on predicted miR-1 targets and evaluated the effect of miR-1 expression on two murine cSCC cell lines, A5 and B9. Following transfection of miR-1, we found decreased mRNA expression of three validated miR-1 targets, Met, Twf1 and Ets1 and one novel target Bag4. Decreased expression of Ets1 was confirmed by Western analysis and by 3’ reporter luciferase assays containing wildtype and mutated Ets1 3’UTR. We evaluated the effect of miR-1 on multiple tumor phenotypes including apoptosis, proliferation, cell cycle and migration. In A5 cells, expression of miR-1 led to decreased proliferation compared to a control miR. miR-1 expression also led to increased apoptosis at later time points (72 and 96 h and to a decrease in cells in S-phase. In summary, we identified five miRNAs with differential expression between cancer resistant and cancer susceptible mice and found that miR-1, a candidate tumor suppressor, has targets with defined roles in tumorigenesis.

  17. Mechanism of Regulatory Effect of MicroRNA-206 on Connexin 43 in Distant Metastasis of Breast Cancer

    Institute of Scientific and Technical Information of China (English)

    Zi-Jing Lin; Jia Ming; Lu Yang; Jun-Ze Du; Ning Wang; Hao-Jun Luo

    2016-01-01

    Background: MicroRNA-206 (miR-206) and connexin 43 (Cx43) are related with the distant metastasis of breast cancer.It remains unclear whether the regulatory effect of miR-206 on Cx43 is involved in metastasis of breast cancer.Methods: Using quantitative real-time polymerase chain reaction and Western blot, the expressions of miR-206 and Cx43 were determined in breast cancer tissues, hepatic and pulmonary metastasis (PM), and cell lines (MCF-10A, MCF-7, and MDA-MB-231).MCF-7/MDA-M-231 cells were transfected with lentivirus-shRNA vectors to enhance/inhibit miR-206, and then Cx43 expression was observed.Cell counting kit-8 assay and Transwell method were used to detect their changes in proliferation, migration, and invasion activity.The mutant plasmids of Cx43-3' untranslated region (3'UTR) at position 478-484 and position 1609-1615 were constructed.Luciferase reporter assay was performed to observe the effects of miR-206 on luciferase expression of different mutant plasmids and to confirm the potential binding sites of Cx43.Results: Cx43 protein expression in hepatic and PM was significantly higher than that in the primary tumor, while no significant difference was showed in messenger RNA (mRNA) expression.MiR-206 mRNA expression in hepatic and PM was significantly lower than that in the primary tumor.Cx43 mRNA and protein levels, as well as cell proliferation, migration, and invasion capabilities, were all significantly improved in MDA-MB-231 cells after reducing miR-206 expression but decreased in MCF-7 cells after elevating miR-206 expression, which demonstrated a significantly negative correlation between miR-206 and Cx43 expression (P =0.03).MiR-206 can drastically decrease Cx43 expression of MCF-7 cells but exerts no effects on Cx43 expression in 293 cells transfected with the Cx43 coding region but the lack of Cx43-3'UTR, suggesting that Cx43-3'UTR may be the key in Cx43 regulated by miR-206.Luciferase expression showed that the inhibition efficiency was

  18. MicroRNA-21-mediated regulation of Sprouty2 protein expression enhances the cytotoxic effect of 5-fluorouracil and metformin in colon cancer cells.

    Science.gov (United States)

    Feng, Yin-Hsun; Wu, Chao-Liang; Shiau, Ai-Li; Lee, Jenq-Chang; Chang, Jan-Gowth; Lu, Pei-Jung; Tung, Chao-Ling; Feng, Li-Yia; Huang, Wen-Tsung; Tsao, Chao-Jung

    2012-05-01

    Sprouty2 (Spry2) was identified recently as a tumor suppressor gene in cancer cells which inhibits the activation of receptor tyrosine kinases (RTKs). The present study explored the effect of Spry2 in colon cancer cells in order to assess its potential use in the treatment of colon cancer. Expression of Spry2 inhibited the growth of a colon cancer cell line, HCT116, and induced sensitization to fluorouracil (5-FU) and metformin. Spry2 promoted apoptosis of cancer cells in association with activation of the phosphatase and tensin homolog deleted on chromosome 10 (PTEN) pathway and the blockade of Ras-Raf-Erk signaling. Treatment of Spry2-HCT116 cells with metformin resulted in a more prominent effect on the inhibition of cell migration. Inhibition of microRNA-21 (mir‑21) induced upregulation of Spry2 and PTEN which underscores the importance of mir-21 in Spry2-associated tumorigenesis of the colon. These results point toward a potential strategy for colon cancer treatment worthy of further investigation. PMID:22322462

  19. An integrative analysis of cellular contexts, miRNAs and mRNAs reveals network clusters associated with antiestrogen-resistant breast cancer cells

    Directory of Open Access Journals (Sweden)

    Nam Seungyoon

    2012-12-01

    Full Text Available Abstract Background A major goal of the field of systems biology is to translate genome-wide profiling data (e.g., mRNAs, miRNAs into interpretable functional networks. However, employing a systems biology approach to better understand the complexities underlying drug resistance phenotypes in cancer continues to represent a significant challenge to the field. Previously, we derived two drug-resistant breast cancer sublines (tamoxifen- and fulvestrant-resistant cell lines from the MCF7 breast cancer cell line and performed genome-wide mRNA and microRNA profiling to identify differential molecular pathways underlying acquired resistance to these important antiestrogens. In the current study, to further define molecular characteristics of acquired antiestrogen resistance we constructed an “integrative network”. We combined joint miRNA-mRNA expression profiles, cancer contexts, miRNA-target mRNA relationships, and miRNA upstream regulators. In particular, to reduce the probability of false positive connections in the network, experimentally validated, rather than prediction-oriented, databases were utilized to obtain connectivity. Also, to improve biological interpretation, cancer contexts were incorporated into the network connectivity. Results Based on the integrative network, we extracted “substructures” (network clusters representing the drug resistant states (tamoxifen- or fulvestrant-resistance cells compared to drug sensitive state (parental MCF7 cells. We identified un-described network clusters that contribute to antiestrogen resistance consisting of miR-146a, -27a, -145, -21, -155, -15a, -125b, and let-7s, in addition to the previously described miR-221/222. Conclusions By integrating miRNA-related network, gene/miRNA expression and text-mining, the current study provides a computational-based systems biology approach for further investigating the molecular mechanism underlying antiestrogen resistance in breast cancer cells. In

  20. Preliminary Analysis of the Expression of Selected Proangiogenic and Antioxidant Genes and MicroRNAs in Patients with Non-Muscle-Invasive Bladder Cancer.

    Science.gov (United States)

    Kozakowska, Magdalena; Dobrowolska-Glazar, Barbara; Okoń, Krzysztof; Józkowicz, Alicja; Dobrowolski, Zygmunt; Dulak, Józef

    2016-01-01

    Heme oxygenase-1 (HO-1) is an enzyme contributing to the development and progression of different cancer types. HO-1 plays a role in pathological angiogenesis in bladder cancer and contributes to the resistance of this cancer to therapy. It also regulates the expression of microRNAs in rhabdomyosarcoma and non-small cell lung cancer. The expression of HO-1 may be regulated by hypoxia inducible factors (HIFs) and Nrf2 transcription factor. The expression of HO-1 has not so far been examined in relation to Nrf2, HIF-1α, and potential mediators of angiogenesis in human bladder cancer. We measured the concentration of proinflammatory and proangiogenic cytokines and the expression of cytoprotective and proangiogenic mRNAs and miRNAs in healthy subjects and patients with bladder cancer. HO-1 expression was upregulated together with HIF-1α, HIF-2α, and Nrf2 in bladder cancer in comparison to healthy tissue. VEGF was elevated both at mRNA and protein level in the tumor and in sera, respectively. Additionally, IL-6 and IL-8 were increased in sera of patients affected with urothelial bladder cancer. Moreover, miR-155 was downregulated whereas miR-200c was elevated in cancer biopsies in comparison to healthy tissue. The results indicate that the increased expression of HO-1 in bladder cancer is paralleled by changes in the expression of other potentially interacting genes, like Nrf2, HIF-1α, HIF-2α, IL-6, IL-8, and VEGF. Further studies are necessary to also elucidate the potential links with miR-155 and miR-200c. PMID:26927195

  1. MicroRNA-155 functions as an OncomiR in breast cancer by targeting the suppressor of cytokine signaling 1 gene.

    Science.gov (United States)

    Jiang, Shuai; Zhang, Hong-Wei; Lu, Ming-Hua; He, Xiao-Hong; Li, Yong; Gu, Hua; Liu, Mo-Fang; Wang, En-Duo

    2010-04-15

    MicroRNA-155 (miR-155) is overexpressed in many human cancers; however, the mechanisms by which miR-155 functions as a putative oncomiR are largely unknown. Here, we report that the tumor suppressor gene suppressor of cytokine signaling 1 (socs1) is an evolutionarily conserved target of miR-155 in breast cancer cells. We found that mir-155 expression is inversely correlated with socs1 expression in breast cancer cell lines as well as in a subset of primary breast tumors. We also identified a 24A-->G mutation in the miR-155 binding site of the SOCS1 3' untranslated region in a breast tumor that reduced miR-155 repression, implicating a mechanism for miRNA targets to avoid repression. Ectopic expression of miR-155 significantly promoted the proliferation of breast cancer cells, the formation of soft agar foci in vitro, and the development of tumors in nude mice. In breast cancer cells, RNA interference silencing of socs1 recapitulates the oncogenic effects of miR-155, whereas restoration of socs1 expression attenuates the protumorigenesis function of miR-155, suggesting that miR-155 exerts its oncogenic role by negatively regulating socs1. Overexpression of miR-155 in breast cancer cells leads to constitutive activation of signal transducer and activator of transcription 3 (STAT3) through the Janus-activated kinase (JAK) pathway, and stimulation of breast cancer cells by the inflammatory cytokines IFN-gamma and interleukin-6 (IL-6), lipopolysaccharide (LPS), and polyriboinosinic:polyribocytidylic acid [poly(I:C)] significantly upregulates mir-155 expression, suggesting that miR-155 may serve as a bridge between inflammation and cancer. Taken together, our study reveals that miR-155 is an oncomiR in breast cancer and that miR-155 may be a potential target in breast cancer therapy. PMID:20354188

  2. MicroRNA expression profiles associated with pancreatic adenocarcinoma and ampullary adenocarcinoma

    DEFF Research Database (Denmark)

    Schultz, Nicolai A; Werner, Jens; Willenbrock, Hanni;

    2012-01-01

    MicroRNAs have potential as diagnostic cancer biomarkers. The aim of this study was (1) to define microRNA expression patterns in formalin-fixed parafin-embedded tissue from pancreatic ductal adenocarcinoma, ampullary adenocarcinoma, normal pancreas and chronic pancreatitis without using micro......, normal pancreas and duodenal adenocarcinoma. In all, 43 microRNAs had higher and 41 microRNAs reduced expression in pancreatic cancer compared with normal pancreas. In all, 32 microRNAs were differently expressed in pancreatic adenocarcinoma compared with chronic pancreatitis (17 higher; 15 reduced......-dissection and (2) to discover new diagnostic microRNAs and combinations of microRNAs in cancer tissue. The expression of 664 microRNAs in tissue from 170 pancreatic adenocarcinomas and 107 ampullary adenocarcinomas were analyzed using a commercial microRNA assay. Results were compared with chronic pancreatitis...

  3. Nuclear factor-κB-dependent microRNA-130a upregulation promotes cervical cancer cell growth by targeting phosphatase and tensin homolog.

    Science.gov (United States)

    Feng, Yeqian; Zhou, Shenghua; Li, Guiyuan; Hu, Chunhong; Zou, Wen; Zhang, Haixia; Sun, Lili

    2016-05-15

    Nuclear factor-κB (NF-κB) may activate a series of gene transcription control cellular signaling pathways whose products are components in a wide range of biological processes. MicroRNAs, a group of non-coding endogenous ones, may regulate gene expression and plays specific roles in tumorigenesis. Using human cervical cancer cell lines, we explored whether NF-κB regulates the expression of microRNA-130a (miR-130a) through binding elements in the miR-130a promoter region. We found that miR-130a accelerates cervical cancer cell proliferation by targeting the phosphatase and tensin homolog on chromosome 10 (PTEN). Further, NF-κB activates both HeLa and CaSki cell growth by upregulating miR-130a. In addition, by targeting PTEN 3' untranslated region, miR-130a might increase cell growth and initiate protein kinase B (AKT) pathway activation. Lastly, PTEN protein was upregulated in response to NF-κB overexpression and downregulated in response to NF-κB inhibition. Compared to total AKT protein level, p-AKT was downregulated by NF-κB overexpression while upregulated by NF-κB inhibition, indicating PTEN pathway activated and affected by NF-κB. Taken together, our findings shed new light on the NF-κB/miR-130a/PTEN pathway in cervical cancer and add new insight regarding the carcinogenesis of cervical cancer. PMID:27040383

  4. MicroRNA modulation in combination with chemotherapeutic drugs as a novel therapeutic strategy for pancreatic cancer

    OpenAIRE

    Caetano, Marta Daniela Passadouro

    2014-01-01

    O adenocarcinoma ductal do pâncreas (ACP) é uma neoplasia altamente agressiva, com um carácter acentuadamente invasivo e um perfil de expressão de microRNAs anormal, que tem sido fortemente associado à malignidade do ACP. A gemcitabina é o fármaco mais utilizado na terapia deste tipo de cancro, embora sem grande impacto na sobrevivência dos pacientes. A falta de tratamentos eficazes para o ACP levou-nos a considerar a possibilidade de usar os microRNAs, como potenciais alvos terapêuticos, no ...

  5. microRNA 21-mediated suppression of Sprouty1 by Pokemon affects liver cancer cell growth and proliferation.

    Science.gov (United States)

    Jin, Xiu-Li; Sun, Qin-Sheng; Liu, Feng; Yang, Hong-Wei; Liu, Min; Liu, Hong-Xia; Xu, Wei; Jiang, Yu-Yang

    2013-07-01

    Transcriptional repressor Pokemon is a critical factor in embryogenesis, development, cell proliferation, differentiation, and oncogenesis, thus behaving as an oncogene. Oncomine database suggests a potential correlation between the expressions of Pokemon and Sprouty1. This study investigated the regulatory role of Pokemon in Sprouty1 expression and the effect on liver cancer cell growth and proliferation, revealing a novel miR-21-mediated regulatory circuit. In normal (HL-7702) and cancer (QGY-7703) liver cell lines, Sprouty1 expression is inversely correlated with Pokemon levels. Targeted expression or siRNA-mediated silencing showed that Pokemon is a repressor of Sprouty1 expression at both mRNA and protein levels, but Pokemon cannot affect the promoter activity of Sprouty1. Sprouty1 is a target of miR-21 and interestingly, we found that miR-21 is up-regulated by Pokemon in liver cancer cells. Luciferase reporter assays showed that Pokemon up-regulated miR-21 transcription in a dose-dependent manner, and ChIP assay exhibited a direct binding of Pokemon to the miR-21 promoter at -747 to -399 bp. Site-directed mutagenesis of the GC boxes at -684 to -679 bp and -652 to -647 bp of miR-21 promoter abolished the regulatory activity by Pokemon. Furthermore, we found that the modulation of Pokemon and miR-21 expression affected the growth and proliferation of liver cancer cells QGY-7703. In summary, our findings demonstrate that Pokemon suppresses Sprouty1 expression through a miR-21-mediated mechanism, affecting the growth and proliferation of liver cancer cells. This study recognized miR-21 and Sprouty1 as novel targets of the Pokemon regulatory network. PMID:23355454

  6. Pathway and network analysis of cancer genomes

    DEFF Research Database (Denmark)

    Creixell, Pau; Reimand, Jueri; Haider, Syed;

    2015-01-01

    Genomic information on tumors from 50 cancer types cataloged by the International Cancer Genome Consortium (ICGC) shows that only a few well-studied driver genes are frequently mutated, in contrast to many infrequently mutated genes that may also contribute to tumor biology. Hence there has been ...

  7. MicroRNA expression profiling to identify and validate reference genes for relative quantification in colorectal cancer

    LENUS (Irish Health Repository)

    Chang, Kah Hoong

    2010-04-29

    Abstract Background Advances in high-throughput technologies and bioinformatics have transformed gene expression profiling methodologies. The results of microarray experiments are often validated using reverse transcription quantitative PCR (RT-qPCR), which is the most sensitive and reproducible method to quantify gene expression. Appropriate normalisation of RT-qPCR data using stably expressed reference genes is critical to ensure accurate and reliable results. Mi(cro)RNA expression profiles have been shown to be more accurate in disease classification than mRNA expression profiles. However, few reports detailed a robust identification and validation strategy for suitable reference genes for normalisation in miRNA RT-qPCR studies. Methods We adopt and report a systematic approach to identify the most stable reference genes for miRNA expression studies by RT-qPCR in colorectal cancer (CRC). High-throughput miRNA profiling was performed on ten pairs of CRC and normal tissues. By using the mean expression value of all expressed miRNAs, we identified the most stable candidate reference genes for subsequent validation. As such the stability of a panel of miRNAs was examined on 35 tumour and 39 normal tissues. The effects of normalisers on the relative quantity of established oncogenic (miR-21 and miR-31) and tumour suppressor (miR-143 and miR-145) target miRNAs were assessed. Results In the array experiment, miR-26a, miR-345, miR-425 and miR-454 were identified as having expression profiles closest to the global mean. From a panel of six miRNAs (let-7a, miR-16, miR-26a, miR-345, miR-425 and miR-454) and two small nucleolar RNA genes (RNU48 and Z30), miR-16 and miR-345 were identified as the most stably expressed reference genes. The combined use of miR-16 and miR-345 to normalise expression data enabled detection of a significant dysregulation of all four target miRNAs between tumour and normal colorectal tissue. Conclusions Our study demonstrates that the top six most

  8. MicroRNA expression profiling to identify and validate reference genes for relative quantification in colorectal cancer.

    LENUS (Irish Health Repository)

    Chang, Kah Hoong

    2010-01-01

    BACKGROUND: Advances in high-throughput technologies and bioinformatics have transformed gene expression profiling methodologies. The results of microarray experiments are often validated using reverse transcription quantitative PCR (RT-qPCR), which is the most sensitive and reproducible method to quantify gene expression. Appropriate normalisation of RT-qPCR data using stably expressed reference genes is critical to ensure accurate and reliable results. Mi(cro)RNA expression profiles have been shown to be more accurate in disease classification than mRNA expression profiles. However, few reports detailed a robust identification and validation strategy for suitable reference genes for normalisation in miRNA RT-qPCR studies. METHODS: We adopt and report a systematic approach to identify the most stable reference genes for miRNA expression studies by RT-qPCR in colorectal cancer (CRC). High-throughput miRNA profiling was performed on ten pairs of CRC and normal tissues. By using the mean expression value of all expressed miRNAs, we identified the most stable candidate reference genes for subsequent validation. As such the stability of a panel of miRNAs was examined on 35 tumour and 39 normal tissues. The effects of normalisers on the relative quantity of established oncogenic (miR-21 and miR-31) and tumour suppressor (miR-143 and miR-145) target miRNAs were assessed. RESULTS: In the array experiment, miR-26a, miR-345, miR-425 and miR-454 were identified as having expression profiles closest to the global mean. From a panel of six miRNAs (let-7a, miR-16, miR-26a, miR-345, miR-425 and miR-454) and two small nucleolar RNA genes (RNU48 and Z30), miR-16 and miR-345 were identified as the most stably expressed reference genes. The combined use of miR-16 and miR-345 to normalise expression data enabled detection of a significant dysregulation of all four target miRNAs between tumour and normal colorectal tissue. CONCLUSIONS: Our study demonstrates that the top six most

  9. Elevated expression of prostate cancer-associated genes is linked to down-regulation of microRNAs

    International Nuclear Information System (INIS)

    Recent evidence suggests that the prostate cancer (PCa)-specific up-regulation of certain genes such as AMACR, EZH2, PSGR, PSMA and TRPM8 could be associated with an aberrant expression of non-coding microRNAs (miRNA). In silico analyses were used to search for miRNAs being putative regulators of PCa-associated genes. The expression of nine selected miRNAs (hsa-miR-101, -138, -186, -224, -26a, -26b, -374a, -410, -660) as well as of the aforementioned PCa-associated genes was analyzed by quantitative PCR using 50 malignant (Tu) and matched non-malignant (Tf) tissue samples from prostatectomy specimens as well as 30 samples from patients with benign prostatic hyperplasia (BPH). Then, correlations between paired miRNA and target gene expression levels were analyzed. Furthermore, the effect of exogenously administered miR-26a on selected target genes was determined by quantitative PCR and Western Blot in various PCa cell lines. A luciferase reporter assay was used for target validation. The expression of all selected miRNAs was decreased in PCa tissue samples compared to either control group (Tu vs Tf: -1.35 to -5.61-fold; Tu vs BPH: -1.17 to -5.49-fold). The down-regulation of most miRNAs inversely correlated with an up-regulation of their putative target genes with Spearman correlation coefficients ranging from -0.107 to -0.551. MiR-186 showed a significantly diminished expression in patients with non-organ confined PCa and initial metastases. Furthermore, over-expression of miR-26a reduced the mRNA and protein expression of its potential target gene AMACR in vitro. Using the luciferase reporter assay AMACR was validated as new target for miR-26a. The findings of this study indicate that the expression of specific miRNAs is decreased in PCa and inversely correlates with the up-regulation of their putative target genes. Consequently, miRNAs could contribute to oncogenesis and progression of PCa via an altered miRNA-target gene-interaction

  10. MicroRNA expression profiling to identify and validate reference genes for relative quantification in colorectal cancer

    International Nuclear Information System (INIS)

    Advances in high-throughput technologies and bioinformatics have transformed gene expression profiling methodologies. The results of microarray experiments are often validated using reverse transcription quantitative PCR (RT-qPCR), which is the most sensitive and reproducible method to quantify gene expression. Appropriate normalisation of RT-qPCR data using stably expressed reference genes is critical to ensure accurate and reliable results. Mi(cro)RNA expression profiles have been shown to be more accurate in disease classification than mRNA expression profiles. However, few reports detailed a robust identification and validation strategy for suitable reference genes for normalisation in miRNA RT-qPCR studies. We adopt and report a systematic approach to identify the most stable reference genes for miRNA expression studies by RT-qPCR in colorectal cancer (CRC). High-throughput miRNA profiling was performed on ten pairs of CRC and normal tissues. By using the mean expression value of all expressed miRNAs, we identified the most stable candidate reference genes for subsequent validation. As such the stability of a panel of miRNAs was examined on 35 tumour and 39 normal tissues. The effects of normalisers on the relative quantity of established oncogenic (miR-21 and miR-31) and tumour suppressor (miR-143 and miR-145) target miRNAs were assessed. In the array experiment, miR-26a, miR-345, miR-425 and miR-454 were identified as having expression profiles closest to the global mean. From a panel of six miRNAs (let-7a, miR-16, miR-26a, miR-345, miR-425 and miR-454) and two small nucleolar RNA genes (RNU48 and Z30), miR-16 and miR-345 were identified as the most stably expressed reference genes. The combined use of miR-16 and miR-345 to normalise expression data enabled detection of a significant dysregulation of all four target miRNAs between tumour and normal colorectal tissue. Our study demonstrates that the top six most stably expressed miRNAs (let-7a, miR-16, miR-26

  11. MicroRNA Seed Region Length Impact on Target Messenger RNA Expression and Survival in Colorectal Cancer

    Science.gov (United States)

    Mullany, Lila E.; Herrick, Jennifer S.; Wolff, Roger K.; Slattery, Martha L.

    2016-01-01

    microRNAs (miRNA) repress messenger RNAs post-transcriptionally through binding to the 3’ UTR of the mRNA with the miRNA seed region. It has been purported that longer seed regions have a greater efficacy on mRNA repression. We tested this hypothesis by evaluating differential expression of miRNAs involved in regulating the immune response, an important mechanism in colorectal cancer (CRC), by seed length category. We subsequently evaluated differential expression of these miRNAs’ targets in colonic tissue and the impact of these miRNAs on CRC survival. We determined sequence complementarity between each miRNA seed region and the 3’ UTR of each experimentally verified mRNA target gene. We classified miRNAs into groups based on seed regions matching perfectly to a mRNA UTR with six bases beginning at position two, seven bases beginning at position one, seven bases beginning at position two, or eight bases beginning at position one. We analyzed these groups in terms of miRNA differential expression between carcinoma and normal colorectal mucosa, differential colonic target mRNA expression, and risk of dying from CRC. After correction for multiple comparisons, the proportion of the miRNAs that were associated with differential mRNA expression was 0% for the 6-mer, 13.64% for the 7α-mer group, 12.82% for the 7β-mer group, and 8.70% for the 8-mer group. The proportion of miRNAs associated with survival was 20% for the 6-mer group, 27.27% for the 7α-mer group, 10.23% for the 7β-mer group, and 21.74% for the 8-mer group. We did not see a linear relationship between seed length and miRNA expression dysregulation, mRNA expression, or survival. Our findings do not support the hypothesis the seed region length alone influences mRNA repression. PMID:27123865

  12. Bioinformatic Studies to Predict MicroRNAs with the Potential of Uncoupling RECK Expression from Epithelial-Mesenchymal Transition in Cancer Cells.

    Science.gov (United States)

    Wang, Zhipeng; Murakami, Ryusuke; Yuki, Kanako; Yoshida, Yoko; Noda, Makoto

    2016-01-01

    RECK is downregulated in many tumors, and forced RECK expression in tumor cells often results in suppression of malignant phenotypes. Recent findings suggest that RECK is upregulated after epithelial-mesenchymal transition (EMT) in normal epithelium-derived cells but not in cancer cells. Since several microRNAs (miRs) are known to target RECK mRNA, we hypothesized that certain miR(s) may be involved in this suppression of RECK upregulation after EMT in cancer cells. To test this hypothesis, we used three approaches: (1) text mining to find miRs relevant to EMT in cancer cells, (2) predicting miR targets using four algorithms, and (3) comparing miR-seq data and RECK mRNA data using a novel non-parametric method. These approaches identified the miR-183-96-182 cluster as a strong candidate. We also looked for transcription factors and signaling molecules that may promote cancer EMT, miR-183-96-182 upregulation, and RECK downregulation. Here we describe our methods, findings, and a testable hypothesis on how RECK expression could be regulated in cancer cells after EMT. PMID:27226706

  13. Bioinformatic Studies to Predict MicroRNAs with the Potential of Uncoupling RECK Expression from Epithelial–Mesenchymal Transition in Cancer Cells

    Science.gov (United States)

    Wang, Zhipeng; Murakami, Ryusuke; Yuki, Kanako; Yoshida, Yoko; Noda, Makoto

    2016-01-01

    RECK is downregulated in many tumors, and forced RECK expression in tumor cells often results in suppression of malignant phenotypes. Recent findings suggest that RECK is upregulated after epithelial-mesenchymal transition (EMT) in normal epithelium-derived cells but not in cancer cells. Since several microRNAs (miRs) are known to target RECK mRNA, we hypothesized that certain miR(s) may be involved in this suppression of RECK upregulation after EMT in cancer cells. To test this hypothesis, we used three approaches: (1) text mining to find miRs relevant to EMT in cancer cells, (2) predicting miR targets using four algorithms, and (3) comparing miR-seq data and RECK mRNA data using a novel non-parametric method. These approaches identified the miR-183-96-182 cluster as a strong candidate. We also looked for transcription factors and signaling molecules that may promote cancer EMT, miR-183-96-182 upregulation, and RECK downregulation. Here we describe our methods, findings, and a testable hypothesis on how RECK expression could be regulated in cancer cells after EMT. PMID:27226706

  14. The gene regulatory network for breast cancer: Integrated regulatory landscape of cancer hallmarks

    Directory of Open Access Journals (Sweden)

    Frank eEmmert-Streib

    2014-02-01

    Full Text Available In this study, we infer the breast cancer gene regulatory network from gene expression data. This network is obtained from the application of the BC3Net inference algorithm to a large-scale gene expression data set consisting of $351$ patient samples. In order to elucidate the functional relevance of the inferred network, we are performing a Gene Ontology (GO analysis for its structural components. Our analysis reveals that most significant GO-terms we find for the breast cancer network represent functional modules of biological processes that are described by known cancer hallmarks, including translation, immune response, cell cycle, organelle fission, mitosis, cell adhesion, RNA processing, RNA splicing and response to wounding. Furthermore, by using a curated list of census cancer genes, we find an enrichment in these functional modules. Finally, we study cooperative effects of chromosomes based on information of interacting genes in the beast cancer network. We find that chromosome $21$ is most coactive with other chromosomes. To our knowledge this is the first study investigating the genome-scale breast cancer network.

  15. MicroRNA: sex steroids, hormonal carcinogenesis, hormonal sensitivity of tumor tissue

    Directory of Open Access Journals (Sweden)

    A. V. Malek

    2015-01-01

    Full Text Available Sex hormones, regulating normal physiological processes of most tissues and organs, are considered to be one of the key factors in the development and progression of the reproductive system cancer. Recently, the importance of the system for post-transcriptional control of gene expression mediated by short single-stranded RNA molecules (microRNA became evident. This system is involved in regulation of normal physiological processes and in the pathogenesis of many diseases, including cancer. In review we discuss the relationship between the two regulatory systems – sex hormones and microRNAs. The relationship of these systems is considered in the context of two tumors – breast and prostate cancer. In particular, the history of research on the role of sex hormones in the pathogenesis of breast cancer and prostate cancer is briefly covered. Additionally, modern scientific data on the biogenesis and biological role of microRNAs are presented in more detail. In the cells of the hormone-sensitive tissues, sex hormones regulate the microRNA-mediated machinery of gene expression control by two known ways: specifically, affecting the activity of individual microRNA molecules and non-specifically by altering the efficiency of microRNA biogenesis and activity of RNA-induced silencing complex. This downstream regulatory network substantially enhances biological effects of sex hormones at physiological conditions. Malignant transformation leads to a distortion of the regulatory effects of sex hormones that crucially influence the system of microRNA-regulated post-transcriptional control of gene expression. The most established and clinically significant example of such phenomenon is the loss of sensitivity of cells to the regulatory action of these hormones. As a consequence, cancer cells acquire the ability to active proliferation without stimulation with sex hormones. This effect is partly mediated by microRNAs. Also, relevant experimental data

  16. Breast cancer stem cells, cytokine networks, and the tumor microenvironment

    OpenAIRE

    Korkaya, Hasan; Liu, Suling; Wicha, Max S.

    2011-01-01

    Many tumors, including breast cancer, are maintained by a subpopulation of cells that display stem cell properties, mediate metastasis, and contribute to treatment resistance. These cancer stem cells (CSCs) are regulated by complex interactions with the components of the tumor microenvironment — including mesenchymal stem cells, adipocytes, tumor associated fibroblasts, endothelial cells, and immune cells — through networks of cytokines and growth factors. Since these components have a direct...

  17. Differential microRNA expression in aristolochic acid-induced upper urothelial tract cancers ex vivo.

    Science.gov (United States)

    Tao, Le; Zeng, Yigang; Wang, Jun; Liu, Zhihong; Shen, Bing; Ge, Jifu; Liu, Yong; Guo, Yifeng; Qiu, Jianxin

    2015-11-01

    Aristolochic acid (AA) is a carcinogenic, mutagenic and nephrotoxic compound commonly isolated from members of the plant family of Aristolochiaceae (such as Aristolochia and Asarum) and used in Chinese herbal medicine. Use of AA and AA‑containing plants causes chronic kidney disease (CKD) and upper urinary tract carcinoma (UUC); however, the underlying mechanism remains to be defined. miRNAs regulate a number of biological processes, including cell proliferation, differentiation and metabolism. This study explored differentially expressed miRNAs between AA‑induced upper urothelial tract cancer (AAN‑UUC) and non‑AAN‑UUC tissues. Patients with AAN‑UUC and non‑AAN‑UUC (n=20/group) were recruited in the present study. Five tissue samples from each group were used for miRNA microarray profiling and the rest of the tissue samples were subjected to reverse transcription-quantitative polymerase chain reaction analysis including seven selected miRNAs for confirmation. A total of 29 miRNAs were differentially expressed between AAN‑UUC and non‑AAN‑UUC tissues (Pontology analyses predicted the functions and targeted genes of these differentially expressed miRNAs, i.e. Akt3, FGFR3, PSEN1, VEGFa and AR. Subsequently, expression of the selected differentially expressed miRNAs (Hsa‑miR‑4795‑5p, Hsa‑miR‑488, Hsa‑miR‑4784, Hsa‑miR‑330, Hsa‑miR‑3916, Hsa‑miR‑4274 and Hsa‑miR‑181c) was validated in another set of tissue samples. A total of 29 miRNAs were identified to be differentially expressed between AAN‑UUC and non‑AAN‑UUC tissues and these miRNA target genes in FGFR3 and Akt pathways, which regulate cell growth and tumor progression, respectively. PMID:26397152

  18. Advances in research on microRNA-21 in colorectal cancer%MicroRNA-21在结直肠癌中的研究进展

    Institute of Scientific and Technical Information of China (English)

    梁政; 周慧芳

    2014-01-01

    结直肠癌是我国常见的消化系统恶性肿瘤之一。目前认为结直肠癌的形成是一个多因素、多步骤的过程,其具体的发病机制尚不清楚。microRNA(miRNA)是一类非编码的小分子 RNA,能在转录后水平调控基因蛋白的表达,参与肿瘤细胞增殖、分化、侵袭和转移,对结直肠癌的发生和发展具有重要的作用。miRNA-21是当前研究miRNA在结直肠癌发病机制的热点之一,本文就miR-21在结直肠癌中的研究进展作一综述。%Colorectal cancer (CRC) is one of the most common digestive system neoplasms in China. Recently, the morbidity and mortality rates of CRC continue to increase with the improvement of people's living standard and the change of the dietary structure. It was accepted that the etiology of colorectal cancer is a multi-factor and multi-step process. However, the mechanism of CRC is still unclear. MicroRNAs (miRNAs) are a class of -21 nucleotide non-coding RNAs and function as a negative regulator of gene expression after transcription, participating in tumor angiogenesis, tumor cell proliferation and invasion. MicroRNA-21 (miR-21), as an important oncogenic RNA, plays a vital role in the development and progression of CRC. This review summarizes the advances in research on miR-21 in colorectal cancer.

  19. Identification of bolting-related microRNAs and their targets reveals complex miRNA-mediated flowering-time regulatory networks in radish (Raphanus sativus L.).

    Science.gov (United States)

    Nie, Shanshan; Xu, Liang; Wang, Yan; Huang, Danqiong; Muleke, Everlyne M; Sun, Xiaochuan; Wang, Ronghua; Xie, Yang; Gong, Yiqin; Liu, Liwang

    2015-01-01

    MicroRNAs (miRNAs) play vital regulatory roles in plant growth and development. The phase transition from vegetative growth to flowering is crucial in the life cycle of plants. To date, miRNA-mediated flowering regulatory networks remain largely unexplored in radish. In this study, two small RNA libraries from radish leaves at vegetative and reproductive stages were constructed and sequenced by Solexa sequencing. A total of 94 known miRNAs representing 21 conserved and 13 non-conserved miRNA families, and 44 potential novel miRNAs, were identified from the two libraries. In addition, 42 known and 17 novel miRNAs were significantly differentially expressed and identified as bolting-related miRNAs. RT-qPCR analysis revealed that some miRNAs exhibited tissue- or developmental stage-specific expression patterns. Moreover, 154 target transcripts were identified for 50 bolting-related miRNAs, which were predominately involved in plant development, signal transduction and transcriptional regulation. Based on the characterization of bolting-related miRNAs and their target genes, a putative schematic model of miRNA-mediated bolting and flowering regulatory network was proposed. These results could provide insights into bolting and flowering regulatory networks in radish, and facilitate dissecting the molecular mechanisms underlying bolting and flowering time regulation in vegetable crops. PMID:26369897

  20. Overexpression of Lin28 Decreases the Chemosensitivity of Gastric Cancer Cells to Oxaliplatin, Paclitaxel, Doxorubicin, and Fluorouracil in Part via microRNA-107.

    Directory of Open Access Journals (Sweden)

    Rongyue Teng

    Full Text Available Higher Lin28 expression is associated with worse pathologic tumor responses in locally advanced gastric cancer patients undergoing neoadjuvant chemotherapy. However, the characteristics of Lin28 and its mechanism of action in chemotherapy resistance is still unclear. In this study, we found that transfection of Lin28 into gastric cancer cells (MKN45 and MKN28 increased their resistance to the chemo-drugs oxaliplatin (OXA, paclitaxel (PTX, doxorubicin (ADM, and fluorouracil (5-Fu compared with gastric cancer cells transfected with a control vector. When knockdown Lin28 expression by Lin28 small interfering RNA (siRNA was evaluated in vitro, we found that the resistance to chemo-drugs was reduced. Furthermore, we found that Lin28 up-regulates C-myc and P-gp and down-regulates Cylin D1. Finally, we found that miR-107 is a target microRNA of Lin28 and that it participates in the mechanism of chemotherapy resistance. Our results suggest that the Lin28/miR-107 pathway could be one of many signaling pathways regulated by Lin28 and associated with gastric cancer chemo-resistance.

  1. An integrative genomic analysis revealed the relevance of microRNA and gene expression for drug-resistance in human breast cancer cells

    Directory of Open Access Journals (Sweden)

    Yamamoto Yusuke

    2011-11-01

    Full Text Available Abstract Background Acquisition of drug-resistance in cancer has led to treatment failure, however, their mechanisms have not been clarified yet. Recent observations indicated that aberrant expressed microRNA (miRNA caused by chromosomal alterations play a critical role in the initiation and progression of cancer. Here, we performed an integrated genomic analysis combined with array-based comparative hybridization, miRNA, and gene expression microarray to elucidate the mechanism of drug-resistance. Results Through genomic approaches in MCF7-ADR; a drug-resistant breast cancer cell line, our results reflect the unique features of drug-resistance, including MDR1 overexpression via genomic amplification and miRNA-mediated TP53INP1 down-regulation. Using a gain of function study with 12 miRNAs whose expressions were down-regulated and genome regions were deleted, we show that miR-505 is a novel tumor suppressive miRNA and inhibits cell proliferation by inducing apoptosis. We also find that Akt3, correlate inversely with miR-505, modulates drug sensitivity in MCF7-ADR. Conclusion These findings indicate that various genes and miRNAs orchestrate to temper the drug-resistance in cancer cells, and thus acquisition of drug-resistance is intricately controlled by genomic status, gene and miRNA expression changes.

  2. De-regulated microRNAs in pediatric cancer stem cells target pathways involved in cell proliferation, cell cycle and development.

    Directory of Open Access Journals (Sweden)

    Patricia C Sanchez-Diaz

    Full Text Available BACKGROUND: microRNAs (miRNAs have been implicated in the control of many biological processes and their deregulation has been associated with many cancers. In recent years, the cancer stem cell (CSC concept has been applied to many cancers including pediatric. We hypothesized that a common signature of deregulated miRNAs in the CSCs fraction may explain the disrupted signaling pathways in CSCs. METHODOLOGY/RESULTS: Using a high throughput qPCR approach we identified 26 CSC associated differentially expressed miRNAs (DEmiRs. Using BCmicrO algorithm 865 potential CSC associated DEmiR targets were obtained. These potential targets were subjected to KEGG, Biocarta and Gene Ontology pathway and biological processes analysis. Four annotated pathways were enriched: cell cycle, cell proliferation, p53 and TGF-beta/BMP. Knocking down hsa-miR-21-5p, hsa-miR-181c-5p and hsa-miR-135b-5p using antisense oligonucleotides and small interfering RNA in cell lines led to the depletion of the CSC fraction and impairment of sphere formation (CSC surrogate assays. CONCLUSION: Our findings indicated that CSC associated DEmiRs and the putative pathways they regulate may have potential therapeutic applications in pediatric cancers.

  3. MicroRNA-376c suppresses non-small-cell lung cancer cell growth and invasion by targeting LRH-1-mediated Wnt signaling pathway.

    Science.gov (United States)

    Jiang, Wenjun; Tian, Ye; Jiang, Shu; Liu, Siyang; Zhao, Xitong; Tian, Dali

    2016-05-13

    MicroRNAs (miRNAs) that negatively regulate gene expression have emerged as novel therapeutic tools for cancer treatment. In this study, we investigated the potential role of Liver receptor homolog-1 (LRH-1), a novel oncogene, in non-small-cell lung cancer (NSCLC), and examined the regulation of LRH-1 by miRNAs. We found that LRH-1 was highly overexpressed in NSCLC cell lines. Knockdown of LRH-1 by small interfering RNA significantly inhibited NSCLC cell growth and invasion. miR-376c directly targeted the 3'-untranslated region (UTR) of LRH-1 and negatively regulated LRH-1 expression, as detected by dual-luciferase reporter assay, real-time quantitative polymerase chain reaction and Western blot analysis. Further data showed that miR-376c expression was inversely correlated with LRH-1 expression in clinical cancer samples. Overexpression of miR-376c could inhibit NSCLC cell growth and invasion as well as Wnt signaling. In contrast, depletion of miR-376c exhibited the opposite effects. Moreover, these effects of miR-376c overexpression were partially abrogated by overexpression of LRH-1. Taken together, these results indicate that LRH-1 is involved in regulating the growth and invasion of NSCLC cells and that miR-376c inhibits NSCLC cell growth and invasion by targeting LRH-1, providing a novel insight into the potential for development of anti-cancer drugs for NSCLC. PMID:27049310

  4. MicroRNA-30a increases tight junction protein expression to suppress the epithelial-mesenchymal transition and metastasis by targeting Slug in breast cancer.

    Science.gov (United States)

    Chang, Chia-Wei; Yu, Jyh-Cherng; Hsieh, Yi-Hsien; Yao, Chung-Chin; Chao, Jui-I; Chen, Po-Ming; Hsieh, Hsiao-Yen; Hsiung, Chia-Ni; Chu, Hou-Wei; Shen, Chen-Yang; Cheng, Chun-Wen

    2016-03-29

    The epithelial-to-mesenchymal (EMT) transition is a prerequisite for conferring metastatic potential during tumor progression. microRNA-30a (miR-30a) expression was significantly lower in aggressive breast cancer cell lines compared with non-invasive breast cancer and non-malignant mammary epithelial cell lines. In contrast, miR-30a overexpression reversed the mesenchymal appearance of cancer cells to result in a cobblestone-like epithelial phenotype. We identified Slug, one of the master regulators of EMT, as a target of miR-30a using in silico prediction. Reporter assays indicated that miR-30a could bind to the 3'-untranslted region of Slug mRNA. Furthermore, we linked miR-30a to increased expression of claudins, a family of tight junction transmembrane proteins. An interaction between Slug and E-box in the claudin promoter sequences was reduced upon miR-30a overexpression, further leading to reduction of filopodia formation and decreased invasiveness/metastasis capabilities of breast cancer cells. Consistently, delivery of miR-30a in xenografted mice decreased tumor invasion and migration. In patients with breast cancer, a significantly elevated risk of the miR-30alow/CLDN2low/FSCNhigh genotype was observed, linking to a phenotypic manifestation of larger tumor size, lymph node metastasis, and advanced tumor stage among patients. In conclusion, the miR-30a/Slug axis inhibits mesenchymal tumor development by interfering with metastatic cancer cell programming and may be a potential target for therapy in breast cancer. PMID:26918943

  5. MicroRNA-204 modulates colorectal cancer cell sensitivity in response to 5-fluorouracil-based treatment by targeting high mobility group protein A2.

    Science.gov (United States)

    Wu, Haijun; Liang, Yu; Shen, Lin; Shen, Liangfang

    2016-01-01

    MicroRNAs (miRNAs) are a conserved class of ∼22 nucleotide RNAs that playing important roles in various biological processes including chemoresistance. Recently, many studies have revealed that miR-204 is significantly attenuated in colorectal cancer (CRC), suggesting that this miRNA may have a function in CRC. However, whether miR-204 modulates chemosensitivity to 5-fluorouracil (5-Fu) in colorectal cancer is still unclear. In our present study, we discuss this possibility and the potential mechanism exerting this effect. We identified high mobility group protein A2 (HMGA2) as a novel direct target of miR-204 and showed that miR-204 expression was decreased while HMGA2 expression was increased in CRC cell lines. Additionally, both MiR-204 overexpression and HMGA2 inhibition attenuated cell proliferation, whereas forced expression of HMGA2 partly restored the inhibitory effect of miR-204 on HCT116 and SW480 cells. Moreover, the miR-204/HMGA2 axis modulated the resistance of tumor cells to 5-Fu in HCT-116 and SW480 colon cancer cells via activation of the PI3K/AKT pathway. These results demonstrate that the miR-204/HMGA2 axis could play a vital role in the 5-Fu resistance of colon cancer cells. Taken together, our present study elucidated that miR-204 upregulated 5-Fu chemosensitivity via the downregulation of HMGA2 in colorectal cancer and provided significant insight into the mechanism of 5-Fu resistance in colorectal cancer patients. More importantly, our present study suggested that miR-204 has potential as a therapeutic strategy for 5-Fu-resistant colorectal cancer. PMID:27095441

  6. MicroRNA-204 modulates colorectal cancer cell sensitivity in response to 5-fluorouracil-based treatment by targeting high mobility group protein A2

    Directory of Open Access Journals (Sweden)

    Haijun Wu

    2016-05-01

    Full Text Available MicroRNAs (miRNAs are a conserved class of ∼22 nucleotide RNAs that playing important roles in various biological processes including chemoresistance. Recently, many studies have revealed that miR-204 is significantly attenuated in colorectal cancer (CRC, suggesting that this miRNA may have a function in CRC. However, whether miR-204 modulates chemosensitivity to 5-fluorouracil (5-Fu in colorectal cancer is still unclear. In our present study, we discuss this possibility and the potential mechanism exerting this effect. We identified high mobility group protein A2 (HMGA2 as a novel direct target of miR-204 and showed that miR-204 expression was decreased while HMGA2 expression was increased in CRC cell lines. Additionally, both MiR-204 overexpression and HMGA2 inhibition attenuated cell proliferation, whereas forced expression of HMGA2 partly restored the inhibitory effect of miR-204 on HCT116 and SW480 cells. Moreover, the miR-204/HMGA2 axis modulated the resistance of tumor cells to 5-Fu in HCT-116 and SW480 colon cancer cells via activation of the PI3K/AKT pathway. These results demonstrate that the miR-204/HMGA2 axis could play a vital role in the 5-Fu resistance of colon cancer cells. Taken together, our present study elucidated that miR-204 upregulated 5-Fu chemosensitivity via the downregulation of HMGA2 in colorectal cancer and provided significant insight into the mechanism of 5-Fu resistance in colorectal cancer patients. More importantly, our present study suggested that miR-204 has potential as a therapeutic strategy for 5-Fu-resistant colorectal cancer.

  7. Phosphoproteome Integration Reveals Patient-Specific Networks in Prostate Cancer.

    OpenAIRE

    Drake, JM; Paull, EO; Graham, NA; Lee, JK; Smith, BA; Titz, B; Stoyanova, T; Faltermeier, CM; Uzunangelov, V; Carlin,, R.; Fleming, DT; Wong, CK; Newton, Y; Sudha, S; Vashisht, AA

    2016-01-01

    We used clinical tissue from lethal metastatic castration-resistant prostate cancer (CRPC) patients obtained at rapid autopsy to evaluate diverse genomic, transcriptomic, and phosphoproteomic datasets for pathway analysis. Using Tied Diffusion through Interacting Events (TieDIE), we integrated differentially expressed master transcriptional regulators, functionally mutated genes, and differentially activated kinases in CRPC tissues to synthesize a robust signaling network consisting of drugga...

  8. Capillary Network, Cancer and Kleiber Law

    CERN Document Server

    Dattoli, G; Licciardi, S; Guiot, C; Deisboeck, T S

    2014-01-01

    We develop a heuristic model embedding Kleiber and Murray laws to describe mass growth, metastasis and vascularization in cancer. We analyze the relevant dynamics using different evolution equations (Verhulst, Gompertz and others). Their extension to reaction diffusion equation of the Fisher type is then used to describe the relevant metastatic spreading in space. Regarding this last point, we suggest that cancer diffusion may be regulated by Levy flights mechanisms and discuss the possibility that the associated reaction diffusion equations are of the fractional type, with the fractional coefficient being determined by the fractal nature of the capillary evolution.

  9. MicroRNA involvement in glioblastoma pathogenesis

    International Nuclear Information System (INIS)

    MicroRNAs are endogenously expressed regulatory noncoding RNAs. Altered expression levels of several microRNAs have been observed in glioblastomas. Functions and direct mRNA targets for these microRNAs have been relatively well studied over the last years. According to these data, it is now evident, that impairment of microRNA regulatory network is one of the key mechanisms in glioblastoma pathogenesis. MicroRNA deregulation is involved in processes such as cell proliferation, apoptosis, cell cycle regulation, invasion, glioma stem cell behavior, and angiogenesis. In this review, we summarize the current knowledge of miRNA functions in glioblastoma with an emphasis on its significance in glioblastoma oncogenic signaling and its potential to serve as a disease biomarker and a novel therapeutic target in oncology.

  10. Effect of MicroRNA-335 on the Metastasis, Invasion and Proliferation of Cells in Patients with Non-small Cell Lung Cancer

    Institute of Scientific and Technical Information of China (English)

    Wang He; Liu Zhili; Wang Zhaoxia

    2013-01-01

    Objective: To investigate the effect of microRNA-335 on the metastasis, invasion and proliferation of cells in patients with non-small-cell lung cancer (NSCLC). Methods:Real-time PCR was performed to detect the expression differences of microRNA-335 between 12 pairs of NSCLC and normal cancerous peripheral tissues, and between SPCA-1 cells of NSCLC and 16HBE of normal pulmonary epithelial cells, while miR-335 expression in SPCA-1 cells were down-regulated and proved by Lipofectamine 2000 transient transfection and real-time PCR, respectively. Scratch test, Transwell invasion assay as well as MTT and clone formation assays were applied to respectively determine the effect of miR-335 on the metastasis, invasion and proliferation of SPCA-1 cells. Results:Compared with para-carcinoma tissues and 16HBE cells, miR-335 expression was evidently higher in NSCLC and SPCA-1 cells. However, it decreased remarkably after transient transfection of anti-miR-335 by SPCA-1 cells with Lipofectamine 2000 for 24 h. Metastasis and invasion of SPCA-1 cells could be inhibited by suppressing miR-335 expression with suppression rates being (42.8±2.7)%and (73.25±4.4)%, respectively. However, the inhibition of miR-335 expression had no effect on the proliferation of SPCA-1 cells. Conclusion:miR-335 expresses highly in NSCLC and its low expression can obviously inhibit the metastasis and invasion of SPCA-1 cells, but has no effect on the proliferation.

  11. The National Cancer Institute's Physical Sciences - Oncology Network

    Science.gov (United States)

    Espey, Michael Graham

    In 2009, the NCI launched the Physical Sciences - Oncology Centers (PS-OC) initiative with 12 Centers (U54) funded through 2014. The current phase of the Program includes U54 funded Centers with the added feature of soliciting new Physical Science - Oncology Projects (PS-OP) U01 grant applications through 2017; see NCI PAR-15-021. The PS-OPs, individually and along with other PS-OPs and the Physical Sciences-Oncology Centers (PS-OCs), comprise the Physical Sciences-Oncology Network (PS-ON). The foundation of the Physical Sciences-Oncology initiative is a high-risk, high-reward program that promotes a `physical sciences perspective' of cancer and fosters the convergence of physical science and cancer research by forming transdisciplinary teams of physical scientists (e.g., physicists, mathematicians, chemists, engineers, computer scientists) and cancer researchers (e.g., cancer biologists, oncologists, pathologists) who work closely together to advance our understanding of cancer. The collaborative PS-ON structure catalyzes transformative science through increased exchange of people, ideas, and approaches. PS-ON resources are leveraged to fund Trans-Network pilot projects to enable synergy and cross-testing of experimental and/or theoretical concepts. This session will include a brief PS-ON overview followed by a strategic discussion with the APS community to exchange perspectives on the progression of trans-disciplinary physical sciences in cancer research.

  12. Design The Cervical Cancer Detector Use The Artificial Neural Network

    International Nuclear Information System (INIS)

    Cancer is one of the contagious diseases that become a public health issue, both in the world and in Indonesia. In the world, 12% of all deaths caused by cancer and is the second killer after cardiovascular disease. Early detection using the IVA is a practical and inexpensive (only requiring acetic acid). However, the accuracy of the method is quite low, as it can not detect the stage of the cancer. While other methods have a better sensitivity than the IVA method, is a method of PAP smear. However, this method is relatively expensive, and requires an experienced pathologist-cytologist. According to the case above, Considered important to make the cancer cervics detector that is used to detect the abnormality and cervical cancer stage and consists of a digital microscope, as well as a computer application based on artificial neural network. The use of cervical cancer detector software and hardware are integrated each other. After the specifications met, the steps to design the cervical cancer detection are: Modifying a conventional microscope by adding a lens, image recording, and the lights, Programming the tools, designing computer applications, Programming features abnormality detection and staging of cancer.

  13. Design The Cervical Cancer Detector Use The Artificial Neural Network

    Science.gov (United States)

    Intan Af'idah, Dwi; Didik Widianto, Eko; Setyawan, Budi

    2013-06-01

    Cancer is one of the contagious diseases that become a public health issue, both in the world and in Indonesia. In the world, 12% of all deaths caused by cancer and is the second killer after cardiovascular disease. Early detection using the IVA is a practical and inexpensive (only requiring acetic acid). However, the accuracy of the method is quite low, as it can not detect the stage of the cancer. While other methods have a better sensitivity than the IVA method, is a method of PAP smear. However, this method is relatively expensive, and requires an experienced pathologist-cytologist. According to the case above, Considered important to make the cancer cervics detector that is used to detect the abnormality and cervical cancer stage and consists of a digital microscope, as well as a computer application based on artificial neural network. The use of cervical cancer detector software and hardware are integrated each other. After the specifications met, the steps to design the cervical cancer detection are: Modifying a conventional microscope by adding a lens, image recording, and the lights, Programming the tools, designing computer applications, Programming features abnormality detection and staging of cancer.

  14. Genetic Networks Lead and Follow Tumor Development: MicroRNA Regulation of Cell Cycle and Apoptosis in the p53 Pathways

    Directory of Open Access Journals (Sweden)

    Kurataka Otsuka

    2014-01-01

    Full Text Available During the past ten years, microRNAs (miRNAs have been shown to play a more significant role in the formation and progression of cancer diseases than previously thought. With an increase in reports about the dysregulation of miRNAs in diverse tumor types, it becomes more obvious that classic tumor-suppressive molecules enter deep into the world of miRNAs. Recently, it has been demonstrated that a typical tumor suppressor p53, known as the guardian of the genome, regulates some kinds of miRNAs to contribute to tumor suppression by the induction of cell-cycle arrest and apoptosis. Meanwhile, miRNAs directly/indirectly control the expression level and activity of p53 to fine-tune its functions or to render p53 inactive, indicating that the interplay between p53 and miRNA is overly complicated. The findings, along with current studies, will underline the continuing importance of understanding this interlocking control system for future therapeutic strategies in cancer treatment and prevention.

  15. Network for Translational Research - Cancer Imaging Program

    Science.gov (United States)

    Cooperative agreement (U54) awards to establish Specialized Research Resource Centers that will participate as members of a network of inter-disciplinary, inter-institutional research teams for the purpose of supporting translational research in optical imaging and/or spectroscopy in vivo, with an emphasis on multiple modalities.

  16. Expression of microRNA-15b and the glycosyltransferase GCNT3 correlates with antitumor efficacy of Rosemary diterpenes in colon and pancreatic cancer.

    Science.gov (United States)

    González-Vallinas, Margarita; Molina, Susana; Vicente, Gonzalo; Zarza, Virginia; Martín-Hernández, Roberto; García-Risco, Mónica R; Fornari, Tiziana; Reglero, Guillermo; Ramírez de Molina, Ana

    2014-01-01

    Colorectal and pancreatic cancers remain important contributors to cancer mortality burden and, therefore, new therapeutic approaches are urgently needed. Rosemary (Rosmarinus officinalis L.) extracts and its components have been reported as natural potent antiproliferative agents against cancer cells. However, to potentially apply rosemary as a complementary approach for cancer therapy, additional information regarding the most effective composition, its antitumor effect in vivo and its main molecular mediators is still needed. In this work, five carnosic acid-rich supercritical rosemary extracts with different chemical compositions have been assayed for their antitumor activity both in vivo (in nude mice) and in vitro against colon and pancreatic cancer cells. We found that the antitumor effect of carnosic acid together with carnosol was higher than the sum of their effects separately, which supports the use of the rosemary extract as a whole. In addition, gene and microRNA expression analyses have been performed to ascertain its antitumor mechanism, revealing that up-regulation of the metabolic-related gene GCNT3 and down-regulation of its potential epigenetic modulator miR-15b correlate with the antitumor effect of rosemary. Moreover, plasmatic miR-15b down-regulation was detected after in vivo treatment with rosemary. Our results support the use of carnosic acid-rich rosemary extract as a complementary approach in colon and pancreatic cancer and indicate that GCNT3 expression may be involved in its antitumor mechanism and that miR-15b might be used as a non-invasive biomarker to monitor rosemary anticancer effect. PMID:24892299

  17. Expression of microRNA-15b and the glycosyltransferase GCNT3 correlates with antitumor efficacy of Rosemary diterpenes in colon and pancreatic cancer.

    Directory of Open Access Journals (Sweden)

    Margarita González-Vallinas

    Full Text Available Colorectal and pancreatic cancers remain important contributors to cancer mortality burden and, therefore, new therapeutic approaches are urgently needed. Rosemary (Rosmarinus officinalis L. extracts and its components have been reported as natural potent antiproliferative agents against cancer cells. However, to potentially apply rosemary as a complementary approach for cancer therapy, additional information regarding the most effective composition, its antitumor effect in vivo and its main molecular mediators is still needed. In this work, five carnosic acid-rich supercritical rosemary extracts with different chemical compositions have been assayed for their antitumor activity both in vivo (in nude mice and in vitro against colon and pancreatic cancer cells. We found that the antitumor effect of carnosic acid together with carnosol was higher than the sum of their effects separately, which supports the use of the rosemary extract as a whole. In addition, gene and microRNA expression analyses have been performed to ascertain its antitumor mechanism, revealing that up-regulation of the metabolic-related gene GCNT3 and down-regulation of its potential epigenetic modulator miR-15b correlate with the antitumor effect of rosemary. Moreover, plasmatic miR-15b down-regulation was detected after in vivo treatment with rosemary. Our results support the use of carnosic acid-rich rosemary extract as a complementary approach in colon and pancreatic cancer and indicate that GCNT3 expression may be involved in its antitumor mechanism and that miR-15b might be used as a non-invasive biomarker to monitor rosemary anticancer effect.

  18. Altered microRNA Expression Profiles and Regulation of INK4A/CDKN2A Tumor Suppressor Genes in Canine Breast Cancer Models.

    Science.gov (United States)

    Lutful Kabir, Farruk Mohammad; DeInnocentes, Patricia; Bird, Richard Curtis

    2015-12-01

    microRNA (miRNA) expression profiling of cancer versus normal cells may reveal the characteristic regulatory features that can be correlated to altered gene expression in both human and animal models of cancers. In this study, the comprehensive expression profiles of the 277 highly characterized miRNAs from the canine genome were evaluated in spontaneous canine mammary tumor (CMT) models harboring defects in a group of cell cycle regulatory and potent tumor suppressor genes of INK4/CDKN2 family including p16/INK4A, p14ARF, and p15/INK4B. A large number of differentially expressed miRNAs were identified in three CMT cell lines to potentially target oncogenes, tumor suppressor genes and cancer biomarkers. A group of the altered miRNAs were identified by miRNA target prediction tools for regulation of the INK4/CDKN2 family tumor suppressor genes. miRNA-141 was experimentally validated for INK4A 3'-UTR target binding in the CMT cell lines providing an essential mechanism for the post-transcriptional regulation of the INK4A tumor suppressor gene in CMT models. A well-recognized group of miRNAs including miR-21, miR-155, miR-9, miR-34a, miR-143/145, and miR-31 were found to be altered in both CMTs and human breast cancer. These altered miRNAs might serve as potential targets for advancing the development of future therapeutic reagents. These findings further strengthen the validity and use of canine breast cancers as appropriate models for the study of human breast cancers. PMID:26095675

  19. Network-based reading system for lung cancer screening CT

    Science.gov (United States)

    Fujino, Yuichi; Fujimura, Kaori; Nomura, Shin-ichiro; Kawashima, Harumi; Tsuchikawa, Megumu; Matsumoto, Toru; Nagao, Kei-ichi; Uruma, Takahiro; Yamamoto, Shinji; Takizawa, Hotaka; Kuroda, Chikazumi; Nakayama, Tomio

    2006-03-01

    This research aims to support chest computed tomography (CT) medical checkups to decrease the death rate by lung cancer. We have developed a remote cooperative reading system for lung cancer screening over the Internet, a secure transmission function, and a cooperative reading environment. It is called the Network-based Reading System. A telemedicine system involves many issues, such as network costs and data security if we use it over the Internet, which is an open network. In Japan, broadband access is widespread and its cost is the lowest in the world. We developed our system considering human machine interface and security. It consists of data entry terminals, a database server, a computer aided diagnosis (CAD) system, and some reading terminals. It uses a secure Digital Imaging and Communication in Medicine (DICOM) encrypting method and Public Key Infrastructure (PKI) based secure DICOM image data distribution. We carried out an experimental trial over the Japan Gigabit Network (JGN), which is the testbed for the Japanese next-generation network, and conducted verification experiments of secure screening image distribution, some kinds of data addition, and remote cooperative reading. We found that network bandwidth of about 1.5 Mbps enabled distribution of screening images and cooperative reading and that the encryption and image distribution methods we proposed were applicable to the encryption and distribution of general DICOM images via the Internet.

  20. Novel and Recently Evolved MicroRNA Clusters Regulate Expansive F-BOX Gene Networks through Phased Small Interfering RNAs in Wild Diploid Strawberry.

    Science.gov (United States)

    Xia, Rui; Ye, Songqing; Liu, Zongrang; Meyers, Blake C; Liu, Zhongchi

    2015-09-01

    The wild strawberry (Fragaria vesca) has recently emerged as an excellent model for cultivated strawberry (Fragaria × ananassa) as well as other Rosaceae fruit crops due to its short seed-to-fruit cycle, diploidy, and sequenced genome. Deep sequencing and parallel analysis of RNA ends were used to identify F. vesca microRNAs (miRNAs) and their target genes, respectively. Thirty-eight novel and 31 known miRNAs were identified. Many known miRNAs targeted not only conserved mRNA targets but also developed new target genes in F. vesca. Significantly, two new clusters of miRNAs were found to collectively target 94 F-BOX (FBX) genes. One of the miRNAs in the new cluster is 22 nucleotides and triggers phased small interfering RNA production from six FBX genes, which amplifies the silencing to additional FBX genes. Comparative genomics revealed that the main novel miRNA cluster evolved from duplications of FBX genes. Finally, conserved trans-acting siRNA pathways were characterized and confirmed with distinct features. Our work identified novel miRNA-FBX networks in F. vesca and shed light on the evolution of miRNAs/phased small interfering RNA networks that regulate large gene families in higher plants. PMID:26143249

  1. Identification by Real-time PCR of 13 mature microRNAs differentially expressed in colorectal cancer and non-tumoral tissues

    Directory of Open Access Journals (Sweden)

    Moreno I

    2006-07-01

    Full Text Available Abstract MicroRNAs (miRNAs are short non-coding RNA molecules playing regulatory roles by repressing translation or cleaving RNA transcripts. Although the number of verified human miRNA is still expanding, only few have been functionally described. However, emerging evidences suggest the potential involvement of altered regulation of miRNA in pathogenesis of cancers and these genes are thought to function as both tumours suppressor and oncogenes. In our study, we examined by Real-Time PCR the expression of 156 mature miRNA in colorectal cancer. The analysis by several bioinformatics algorithms of colorectal tumours and adjacent non-neoplastic tissues from patients and colorectal cancer cell lines allowed identifying a group of 13 miRNA whose expression is significantly altered in this tumor. The most significantly deregulated miRNA being miR-31, miR-96, miR-133b, miR-135b, miR-145, and miR-183. In addition, the expression level of miR-31 was correlated with the stage of CRC tumor. Our results suggest that miRNA expression profile could have relevance to the biological and clinical behavior of colorectal neoplasia.

  2. Metformin induces apoptosis by microRNA-26a-mediated downregulation of myeloid cell leukaemia-1 in human oral cancer cells.

    Science.gov (United States)

    Wang, Fang; Xu, Jincheng; Liu, Hao; Liu, Zhe; Xia, Fei

    2016-06-01

    In recent years, population-based studies and retrospective analyses of clinical studies have shown that metformin treatment is associated with reduced cancer incidence and a decrease in cancer‑associated mortality. However, its mechanism of action remains to be fully understood. The present study demonstrates the effects of metformin on KB human oral cancer cells and explores the role of myeloid cell leukaemia‑1 (Mcl‑1) in metformin‑induced mitochondria‑dependent cellular apoptosis. It was demonstrated that metformin exposure caused significant suppression of KB cell proliferation and induced cell death. Furthermore, metformin induced apoptosis through the downregulation of Mcl‑1 in KB human oral cancer cells, and the overexpression of Mcl‑1 in metformin‑treated KB cells significantly increased cell viability. Consistently, Bax and Bim were upregulated in metformin‑treated cells. The results also reveal that microRNA (miR)‑26a expression was markedly increased by metformin. Subsequent to enforced miR‑26a expression in KB cells using miR‑26a mimics, cell viability and the level of Mcl‑1 decreased. These results suggest that the anti‑proliferative effects of metformin in KB cells may result partly from induction of apoptosis by miR-26a-induced downregulation of Mcl-1. PMID:27082123

  3. EGF induces microRNAs that target suppressors of cell migration: miR-15b targets MTSS1 in breast cancer.

    Science.gov (United States)

    Kedmi, Merav; Ben-Chetrit, Nir; Körner, Cindy; Mancini, Maicol; Ben-Moshe, Noa Bossel; Lauriola, Mattia; Lavi, Sara; Biagioni, Francesca; Carvalho, Silvia; Cohen-Dvashi, Hadas; Schmitt, Fernando; Wiemann, Stefan; Blandino, Giovanni; Yarden, Yosef

    2015-03-17

    Growth factors promote tumor growth and metastasis. We found that epidermal growth factor (EGF) induced a set of 22 microRNAs (miRNAs) before promoting the migration of mammary cells. These miRNAs were more abundant in human breast tumors relative to the surrounding tissue, and their abundance varied among breast cancer subtypes. One of these miRNAs, miR-15b, targeted the 3' untranslated region of MTSS1 (metastasis suppressor protein 1). Although xenografts in which MTSS1 was knocked down grew more slowly in mice initially, longer-term growth was unaffected. Knocking down MTSS1 increased migration and Matrigel invasion of nontransformed mammary epithelial cells. Overexpressing MTSS1 in an invasive cell line decreased cell migration and invasiveness, decreased the formation of invadopodia and actin stress fibers, and increased the formation of cellular junctions. In tissues from breast cancer patients with the aggressive basal subtype, an inverse correlation occurred with the high expression of miRNA-15b and the low expression of MTSS1. Furthermore, low abundance of MTSS1 correlated with poor patient prognosis. Thus, growth factor-inducible miRNAs mediate mechanisms underlying the progression of cancer. PMID:25783158

  4. microRNA-34a-Upregulated Retinoic Acid-Inducible Gene-I Promotes Apoptosis and Delays Cell Cycle Transition in Cervical Cancer Cells.

    Science.gov (United States)

    Wang, Jing-Hua; Zhang, Le; Ma, Yu-Wei; Xiao, Jing; Zhang, Yi; Liu, Min; Tang, Hua

    2016-06-01

    The function of retinoic acid-inducible gene-I (RIG-I) in viral replication is well documented, but its function in carcinogenesis and malignancies as well as relationship with microRNAs (miRNAs) remain poorly understood. miR-34a is an antioncogene in multiple tumors. In our study, RIG-I and miR-34a suppressed cell growth, proliferation, migration, and invasion in cervical cancer cells in vitro. miR-34a was validated as a new regulator of RIG-I by binding to its 3' untranslated region and upregulating its expression level. Furthermore, we revealed that RIG-I and miR-34a enhanced apoptosis, delayed the G1/S/G2 transition of the cell cycle, and inhibited the epithelial-mesenchymal transition process to modulate malignancies in cervical cancer cells. Phenotypic rescue experiments indicated that RIG-I mediates the effects of miR-34a in HeLa and C33A cells. These findings provide new insights into the mechanisms that underlie carcinogenesis and may provide new biomarkers for the diagnosis and therapy of cervical cancer. PMID:26910120

  5. MicroRNA-194 restrains the cell progression of non-small cell lung cancer by targeting human nuclear distribution protein C.

    Science.gov (United States)

    Zhou, Lirong; Di, Qingguo; Sun, Baohua; Wang, Xiaosheng; Li, Min; Shi, Jian

    2016-06-01

    NSCLC accounts for over 80% of all lung cancers and is associated with poor prognosis. Human nuclear distribution C (hNUDC) was predicted to be the target gene of microRNA-194 (miR-194). The present study was designed to demonstrate the mechanism of miR-194 in the regulation of non-small cell lung cancer (NSCLC) via targeting the hNUDC. The hNUDC expression was found to strongly be increased while the miR-194 decreased significantly in the NSCLC cell lines when compared with the healthy controls. Moreover, the luciferase report confirmed the targeting reaction between miR-194 and hNUDC. After transfection with miR-194 mimic into NSCLC cells, we found that the miR-194 overexpression resulted in abnormal nuclear division, decreased cell proliferation and inhibited the expression of hNUDC and Mpl/ERK pathway proteins. Furthermore, the hNUDC overexpression affected the suppression effect of miR-194 in 95D cells, indicating that miR-194 suppresses tumor cell process by inhibiting the hNUDC expression. In brief, the present study suggests that the upregulation of miR-194 affects the hNUDC expression, leading to a downregulated expression of Mpl/ERK pathway proteins, and suppresses the mitosis and proliferation of NSCLC cells. These results offer a potential therapeutic strategy for the treatment of lung cancer. PMID:27035759

  6. Evolution and Controllability of Cancer Networks: A Boolean Perspective.

    Science.gov (United States)

    Srihari, Sriganesh; Raman, Venkatesh; Leong, Hon Wai; Ragan, Mark A

    2014-01-01

    Cancer forms a robust system capable of maintaining stable functioning (cell sustenance and proliferation) despite perturbations. Cancer progresses as stages over time typically with increasing aggressiveness and worsening prognosis. Characterizing these stages and identifying the genes driving transitions between them is critical to understand cancer progression and to develop effective anti-cancer therapies. In this work, we propose a novel model for the `cancer system' as a Boolean state space in which a Boolean network, built from protein-interaction and gene-expression data from different stages of cancer, transits between Boolean satisfiability states by "editing" interactions and "flipping" genes. Edits reflect rewiring of the PPI network while flipping of genes reflect activation or silencing of genes between stages. We formulate a minimization problem min flip to identify these genes driving the transitions. The application of our model (called BoolSpace) on three case studies-pancreatic and breast tumours in human and post spinal-cord injury (SCI) in rats-reveals valuable insights into the phenomenon of cancer progression: (i) interactions involved in core cell-cycle and DNA-damage repair pathways are significantly rewired in tumours, indicating significant impact to key genome-stabilizing mechanisms; (ii) several of the genes flipped are serine/threonine kinases which act as biological switches, reflecting cellular switching mechanisms between stages; and (iii) different sets of genes are flipped during the initial and final stages indicating a pattern to tumour progression. Based on these results, we hypothesize that robustness of cancer partly stems from "passing of the baton" between genes at different stages-genes from different biological processes and/or cellular components are involved in different stages of tumour progression thereby allowing tumour cells to evade targeted therapy, and therefore an effective therapy should target a "cover set" of

  7. Prediction of oncogenic interactions and cancer-related signaling networks based on network topology.

    Directory of Open Access Journals (Sweden)

    Marcio Luis Acencio

    Full Text Available Cancer has been increasingly recognized as a systems biology disease since many investigators have demonstrated that this malignant phenotype emerges from abnormal protein-protein, regulatory and metabolic interactions induced by simultaneous structural and regulatory changes in multiple genes and pathways. Therefore, the identification of oncogenic interactions and cancer-related signaling networks is crucial for better understanding cancer. As experimental techniques for determining such interactions and signaling networks are labor-intensive and time-consuming, the development of a computational approach capable to accomplish this task would be of great value. For this purpose, we present here a novel computational approach based on network topology and machine learning capable to predict oncogenic interactions and extract relevant cancer-related signaling subnetworks from an integrated network of human genes interactions (INHGI. This approach, called graph2sig, is twofold: first, it assigns oncogenic scores to all interactions in the INHGI and then these oncogenic scores are used as edge weights to extract oncogenic signaling subnetworks from INHGI. Regarding the prediction of oncogenic interactions, we showed that graph2sig is able to recover 89% of known oncogenic interactions with a precision of 77%. Moreover, the interactions that received high oncogenic scores are enriched in genes for which mutations have been causally implicated in cancer. We also demonstrated that graph2sig is potentially useful in extracting oncogenic signaling subnetworks: more than 80% of constructed subnetworks contain more than 50% of original interactions in their corresponding oncogenic linear pathways present in the KEGG PATHWAY database. In addition, the potential oncogenic signaling subnetworks discovered by graph2sig are supported by experimental evidence. Taken together, these results suggest that graph2sig can be a useful tool for investigators involved

  8. A double feedback loop mediated by microRNA-23a/27a/24-2 regulates M1 versus M2 macrophage polarization and thus regulates cancer progression.

    Science.gov (United States)

    Ma, Sisi; Liu, Min; Xu, Zhenbiao; Li, Yanshuang; Guo, Hui; Ge, Yehua; Liu, Yanxin; Zheng, Dexian; Shi, Juan

    2016-03-22

    In response to microenvironmental signals, macrophages undergo different types of activation, including the "classic" pro-inflammatory phenotype (also called M1) and the "alternative" anti-inflammatory phenotype (also called M2). Macrophage polarized activation has profound effects on immune and inflammatory responses, but mechanisms underlying the various types of macrophage is still in its infancy. In this study, we reported that M1-type stimulation could down-regulate miR-23a/27a/24-2 cluster transcription through the binding of NF-κB to this cluster's promoter and that miR-23a in turn activated the NF-κB pathway by targeting A20 and thus promoted the production of pro-inflammatory cytokines. Furthermore, STAT6 occupied the miR-23a/27a/24-2 cluster promoter and activated their transcription in IL-4-stimulated macrophages. In addition, miR-23a in turn suppressed the JAK1/STAT-6 pathway and reduced the production of M2 type cytokines by targeting JAK1 and STAT-6 directly, while miR-27a showed the same phenotype by targeting IRF4 and PPAR-γ. The miR-23a/27a/24-2 cluster was shown to be significantly decreased in TAMs of breast cancer patients, and macrophages overexpressing the miR-23a/27a/24-2 cluster inhibited tumor growth in vivo. Taken together, these data integrated microRNA expression and function into macrophage polarization networks and identified a double feedback loop consisting of the miR-23a/27a/24-2 cluster and the key regulators of the M1 and M2 macrophage polarization pathway. Moreover, miR-23a/27a/24-2 regulates the polarization of tumor-associated macrophages and thus promotes cancer progression. PMID:26540574

  9. microRNA as a potential vector for the propagation of robustness in protein expression and oscillatory dynamics within a ceRNA network.

    Directory of Open Access Journals (Sweden)

    Claude Gérard

    Full Text Available microRNAs (miRNAs are small noncoding RNAs that are important post-transcriptional regulators of gene expression. miRNAs can induce thresholds in protein synthesis. Such thresholds in protein output can be also achieved by oligomerization of transcription factors (TF for the control of gene expression. First, we propose a minimal model for protein expression regulated by miRNA and by oligomerization of TF. We show that miRNA and oligomerization of TF generate a buffer, which increases the robustness of protein output towards molecular noise as well as towards random variation of kinetics parameters. Next, we extend the model by considering that the same miRNA can bind to multiple messenger RNAs, which accounts for the dynamics of a minimal competing endogenous RNAs (ceRNAs network. The model shows that, through common miRNA regulation, TF can control the expression of all proteins formed by the ceRNA network, even if it drives the expression of only one gene in the network. The model further suggests that the threshold in protein synthesis mediated by the oligomerization of TF can be propagated to the other genes, which can increase the robustness of the expression of all genes in such ceRNA network. Furthermore, we show that a miRNA could increase the time delay of a "Goodwin-like" oscillator model, which may favor the occurrence of oscillations of large amplitude. This result predicts important roles of miRNAs in the control of the molecular mechanisms leading to the emergence of biological rhythms. Moreover, a model for the latter oscillator embedded in a ceRNA