MP29-16 ROLE OF A NOVEL TUMOR SUPPRESSOR MICRO-RNA IN PROSTATE CANCER.

Abstract

You have accessJournal of UrologyProstate Cancer: Basic Research & Pathophysiology I1 Apr 2018MP29-16 ROLE OF A NOVEL TUMOR SUPPRESSOR MICRO-RNA IN PROSTATE CANCER. Nadeem Bhat, Varahram Shahryari, Sharanjot Saini, Soichiro Yamamura, Yuichiro Tanaka, Rajvir Dahiya, and Shahana Majid Nadeem BhatNadeem Bhat More articles by this author , Varahram ShahryariVarahram Shahryari More articles by this author , Sharanjot SainiSharanjot Saini More articles by this author , Soichiro YamamuraSoichiro Yamamura More articles by this author , Yuichiro TanakaYuichiro Tanaka More articles by this author , Rajvir DahiyaRajvir Dahiya More articles by this author , and Shahana MajidShahana Majid More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2018.02.936AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Prostate cancer is the most frequently diagnosed malignant tumor and third-leading cause of cancer deaths in American men. MicroRNAs are small noncoding RNAs that regulate the expression of >60% of all human genes, either inhibiting target mRNA translation or inducing its degradation. MicroRNAs act as tumor suppressors or oncogenes in various cancers. The main objective of this study was to investigate the role of miR-588 in prostate cancer. METHODS We employed a comprehensive approach using a panel of cell lines, in house tissue samples, publicly available large data sets such as TCGA, a series of in vitro assays such as quantitative-real time PCR; western blot; fluorescence-activated cell sorting assays for cell cycle distribution and apoptosis; assays for cell viability, migration and invasion assays. Luciferase reporter assays and in-vivo intra-cardiac study in nude mice was also performed. RESULTS The expression of miR-588 was significantly suppressed or silenced in prostate cancer tissue samples and cell lines when compared with normal tissues and a non-malignant cell line. Similar results were observed by analyzing the publicly available TCGA data sets for prostate adenocarcinoma. Functionally ectopic expression of miR-588 induced G0/G1 cell cycle arrest and apoptosis and suppressed cell proliferation. miR-588 exerted these functional effects by directly targeting the oncogenic Cyclin A2 that is involved in cancer cell cycle and proliferation. In silico algorithm showed a complimentary binding sequence in the 3'UTR of Cyclin A2 for miR-588. Over-expression of miR-588 significantly suppressed the luciferase activity of reporter plasmid containing the wild type 3'UTR sequences of Cyclin A2 complementary to miR-588, which was abolished by mutations in these 3'UTR regions. miR-588 overexpression also significantly reduced the expression of Cyclin A2 at both mRNA and protein levels. A significant decrease in the expression of various cell cycle pathway genes such as CycE1, MCM2, MCM4, CDC7 and CDT1 was also observed. These genes are involved in promoting cell cycle and proliferation and are overexpressed in prostate cancer. In vivo intracardiac implantation of PC3-MLuc-C6 prostate cancer cells constitutively expressing miR-588 showed a significant inhibition of the metastatic dissemination of these cells compared to the control miR expressing cells. CONCLUSIONS This is the first study demonstrating that miR-588 is significantly silenced and acts as a tumor suppressor in prostate cancer. Reconstitution of silenced miR-588 may lead to the down-regulation of target oncogenes thereby contributing to novel therapeutic approaches for regulating prostate cancer. © 2018FiguresReferencesRelatedDetails Volume 199Issue 4SApril 2018Page: e371-e372 Advertisement Copyright & Permissions© 2018MetricsAuthor Information Nadeem Bhat More articles by this author Varahram Shahryari More articles by this author Sharanjot Saini More articles by this author Soichiro Yamamura More articles by this author Yuichiro Tanaka More articles by this author Rajvir Dahiya More articles by this author Shahana Majid More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...