MP88-01 DUAL TUMOR-SUPPRESSORS MIR-139-5P/-3P DERIVED FROM PRE-MIR-139 VIA TARGETING MATRIX METALLOPROTEASE 11 (MMP11) IN BLADDER CANCER

Abstract

You have accessJournal of UrologyBladder Cancer: Basic Research & Pathophysiology V1 Apr 2016MP88-01 DUAL TUMOR-SUPPRESSORS MIR-139-5P/-3P DERIVED FROM PRE-MIR-139 VIA TARGETING MATRIX METALLOPROTEASE 11 (MMP11) IN BLADDER CANCER Masaya Yonemori, Naohiko Seki, Ryosuke Matsushita, Kazutaka Miyamoto, Hirofumi Yoshino, Yusuke Goto, Mayuko Kato, Akira Kurozumi, Masayuki Nakagawa, and Hideki Enokida Masaya YonemoriMasaya Yonemori More articles by this author , Naohiko SekiNaohiko Seki More articles by this author , Ryosuke MatsushitaRyosuke Matsushita More articles by this author , Kazutaka MiyamotoKazutaka Miyamoto More articles by this author , Hirofumi YoshinoHirofumi Yoshino More articles by this author , Yusuke GotoYusuke Goto More articles by this author , Mayuko KatoMayuko Kato More articles by this author , Akira KurozumiAkira Kurozumi More articles by this author , Masayuki NakagawaMasayuki Nakagawa More articles by this author , and Hideki EnokidaHideki Enokida More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.2419AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The 5-year survival rate for patients with muscle invasive bladder cancer (BC) is approximately 60%, and patients with lymph node metastases die in the first 5 years after diagnosis. To improve the survival rate for patients with advanced BC, novel treatment strategies based on the current genomic approaches are needed. Our recent study of microRNA (miRNA) expression signature of BC by deep-sequencing revealed that miR-139-5p (guide strand) and miR-139-3p (passenger strand) derived from pre-miR-139 were significantly downregulated in BC tissues. In miRNA biogenesis, during RISC loading the passenger strand of miRNA duplex is discarded, while the guide strand is retained to direct recruitment of the RISC to target mRNAs. We hypothesis that these miRNAs function as tumor suppressors in BC. The aim of the present study was to investigate the functional roles of these miRNAs and their modulation of cancer networks in BC cells. METHODS Expression levels of miR-139-5p/-3p and its candidate target genes were evaluated in two BC cell lines (T24 and BOY) and BC clinical specimens (62 BCs and 23 normal bladder epitheliums: NBEs) by qRT-PCR methods. For the gain of function study, proliferation, migration, and invasion were performed in miR-139-5p/-3p transfected BC cell lines. Putative target genes were determined by the analyses with GEO database and miR139-5p/-3p transfected T24 microarray study. Loss of function study for its target gene was examined. Overall survival between high and low expression of the target gene was analyzed by the Kaplan-Meier method. RESULTS The expression levels of miR-139-5p/-3p were reduced in tumor tissues and BC cell lines compared with NBEs (P < 0.0001). Restoration of miR-139-5p or miR-139-3p in cancer cells revealed that both miRNAs inhibited cancer cell migration and invasion. Our data demonstrated that MMP11 was a direct target. Silencing of MMP11 inhibited cell migration and invasion by BC cells. Moreover, Kaplan-Meier analysis revealed that the patients with high MMP11 expression had lower overall survival probabilities than those with low expression (p=0.043). CONCLUSIONS To the best of our knowledge, this is the first report demonstrating that dual tumor-suppressive roles of the miR-139-5p and miR-139-3p in BC cells, and these miRNAs directly regulated MMP11. The identification of target gene regulated by novel tumor-suppressive miRNAs may lead to a better understanding of molecular mechanisms of BC metastatic pathways and the development of new therapeutic strategies to treat this disease. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e1129 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Masaya Yonemori More articles by this author Naohiko Seki More articles by this author Ryosuke Matsushita More articles by this author Kazutaka Miyamoto More articles by this author Hirofumi Yoshino More articles by this author Yusuke Goto More articles by this author Mayuko Kato More articles by this author Akira Kurozumi More articles by this author Masayuki Nakagawa More articles by this author Hideki Enokida More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...