790 EXPRESSION SIGNATURE OF TUMOR-SUPPRESSIVE MIRNA AND CONTROL OF CANCER ASSOCIATED MOLECULAR PATHWAYS IN PROSTATE CANCER

Abstract

You have accessJournal of UrologyProstate Cancer: Basic Research (IV)1 Apr 2013790 EXPRESSION SIGNATURE OF TUMOR-SUPPRESSIVE MIRNA AND CONTROL OF CANCER ASSOCIATED MOLECULAR PATHWAYS IN PROSTATE CANCER Satoko Kojima, Hideki Enokida, Hirohumi Yoshino, Takeshi Chiyomaru, Takashi Kinoshita, Miki Fuse, Yukio Naya, Masayuki Nakagawa, and Naohiko Seki Satoko KojimaSatoko Kojima Ichihara, Japan More articles by this author , Hideki EnokidaHideki Enokida Kagoshima, Japan More articles by this author , Hirohumi YoshinoHirohumi Yoshino Kagoshima, Japan More articles by this author , Takeshi ChiyomaruTakeshi Chiyomaru Kagoshima, Japan More articles by this author , Takashi KinoshitaTakashi Kinoshita Chiba, Japan More articles by this author , Miki FuseMiki Fuse Chiba, Japan More articles by this author , Yukio NayaYukio Naya Ichihara, Japan More articles by this author , Masayuki NakagawaMasayuki Nakagawa Kagoshima, Japan More articles by this author , and Naohiko SekiNaohiko Seki Chiba, Japan More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2013.02.354AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES miRNAs are aberrantly expressed in many human cancers and can function as tumor suppressors or oncogenes that target many cancer-related genes. Therefore, genome-wide comprehensive study is necessary for decoding tumor suppressive miRNA-mediated molecular pathways in cancer research field. In this study we identified tumor suppressive miRNAs in prostate cancer (PCa) based on the miRNA expression signature in clinical PCa specimens and seek out of the tumor suppressive miRNA-mediated molecular pathways. METHODS The miRNA expression signature of PCa was applied to screen 778 miRNAs by the TaqMan LDA Human microRNA® using five PCa tissues and five non-cancerous tissues. Gain-of-function studies were performed to investigate cancer cell proliferation, migration and invasion by restoration of mature miRNAs/siRNA into PCa cell lines. To identify the biological processes or pathways potentially regulated by the miRNAs, we applied gene expression data and in silico analysis using TargetScan database [http://www.targetscan.org/] and GENECODIS software. The GENECODIS software assigned a number of the putative miRNA targets to known pathways in KEGG [http://www.genome.jp/kegg/pathway.html]. RESULTS The miRNA expression signature in PCa showed that 56 miRNAs were significantly down-regulated in PCa compared to non-PCa tissues. Among them, the functional screening of down-regulated miRNAs demonstrated that miR-222, miR-31, miR-133a and miR-1 inhibited cell proliferation, invasion, and migration in PCa cell lines (PC3 and DU145), suggesting that these miRNAs may act as tumor suppressors in PCa. Our in silico analysis showed that these tumor suppressive miRNAs appeared to be an important modulator of tumor cell processes through suppression of many targets, particularly those involved in focal adhesion, MAPK and ErbB signaling pathways. CONCLUSIONS Aberrant expression of miRNAs has shed light on recent miRNA signatures and identification of tumor suppressive miRNA mediated novel molecular pathways in PCa. Tumor suppressive miRNA-mediated novel molecular pathways provide a new insight of PCa oncogenesis and metastasis. Furthermore, miRNA-mediated pathways contribute to discovery of molecular target search of PCa treatments. © 2013 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 189Issue 4SApril 2013Page: e326 Advertisement Copyright & Permissions© 2013 by American Urological Association Education and Research, Inc.MetricsAuthor Information Satoko Kojima Ichihara, Japan More articles by this author Hideki Enokida Kagoshima, Japan More articles by this author Hirohumi Yoshino Kagoshima, Japan More articles by this author Takeshi Chiyomaru Kagoshima, Japan More articles by this author Takashi Kinoshita Chiba, Japan More articles by this author Miki Fuse Chiba, Japan More articles by this author Yukio Naya Ichihara, Japan More articles by this author Masayuki Nakagawa Kagoshima, Japan More articles by this author Naohiko Seki Chiba, Japan More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...