PD38-04 DUAL TUMOR-SUPPRESSORS (MIR-145-5P/MIR-145-3P) INDUCING CANCER CELL APOPTOSIS VIA DIRECT TARGETING UHRF1 IN BLADDER CANCER

Abstract

You have accessJournal of UrologyBladder Cancer: Basic Research & Pathophysiology III1 Apr 2016PD38-04 DUAL TUMOR-SUPPRESSORS (MIR-145-5P/MIR-145-3P) INDUCING CANCER CELL APOPTOSIS VIA DIRECT TARGETING UHRF1 IN BLADDER CANCER Ryosuke Matsushita, Naohiko Seki, Hirofumi Yoshino, Kazutaka Miyamoto, Masaya Yonemori, Akira Kurozumi, Mayuko Kato, Hideki Enokida, and Masayuki Nakagawa Ryosuke MatsushitaRyosuke Matsushita More articles by this author , Naohiko SekiNaohiko Seki More articles by this author , Hirofumi YoshinoHirofumi Yoshino More articles by this author , Kazutaka MiyamotoKazutaka Miyamoto More articles by this author , Masaya YonemoriMasaya Yonemori More articles by this author , Akira KurozumiAkira Kurozumi More articles by this author , Mayuko KatoMayuko Kato More articles by this author , Hideki EnokidaHideki Enokida More articles by this author , and Masayuki NakagawaMasayuki Nakagawa More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.1484AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Drugs in GEMCITABINS-CISPLATIN combination treatment has adapted for the first-line therapy of patients with advanced bladder cancer (BC). However, the response rate in this treatment is restrictive for advanced BC and no effective second-line chemotherapeutic regimen is available as of now. The development of the new treatment regimens based on the current genomics approach is required for BC. Our recent study of microRNA (miRNA) expression signature by deep sequencing revealed that miR-145-5p and miR-145-3p were significantly reduced in BC tissues compared with normal bladder epithelium. In miRNA biogenesis, during RISC loading one strand (passenger strand) of miRNA duplex is discarded, while the other strand (guide strand) is retained to direct recruitment of the RISC to target mRNAs. Our deep sequencing data suggested that both strands of pre-miRNA-145, miR-145-5p and miR-145-3p act as tumor-suppressors in BC cells. The aim of the present study was to investigate the functional significance of miR-145-5p and miR-145-3p in BC cells and to identify these miRNAs mediated target genes involved in BC oncogenesis and metastasis. METHODS Expression levels of miR-145-5p/3p and its target gene in clinical tissues (71 BCs and 12 normal bladder epithelia) and cell lines ( T24 and BOY ) were evaluated by qRT-PCR. The functional studies of these miRNAs and the target genes were performed by cell proliferation, migration, invasion, and apoptosis assays in BC cell lines. Genome-wide gene expression analysis and in silico analysis using microRNA.org and GEO database, were applied to investigate molecular target regulated by these miRNAs. A luciferase reporter assay was carried out to determine whether 3' UTR of target gene have actual biding sites for these miRNAs. RESULTS The expression levels of miR-145-5p/3p were significantly reduced in BC tissues and the cell lines (p<0.0001). Restoration of these miRNAs revealed that both miRNAs significantly induced apoptosis and inhibited proliferation, migration, and invasion (p<0.0001). Ubiquitin-like, containing PHD and RING finger domains 1 (UHRF1) was identified as a direct target gene of miR-145-5p/3p by luciferase reporter assays. CONCLUSIONS Two mature miRNAs, miR-145-5p and miR-145-3p derived from pre-miR-145 act as tumor-suppressors in BC cells. UHRF1 expression was regulated by miR-145-5p and miR-145-3p in BC cells, and aberrant expression of UHRF1 might be enhanced BC metastasis. Identification of novel target gene regulated by dual tumor-suppressors miR-145-5p and miR-145p-3p may lead to a better understanding of BC and the development of new therapeutic strategies to treat this disease. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e924-e925 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Ryosuke Matsushita More articles by this author Naohiko Seki More articles by this author Hirofumi Yoshino More articles by this author Kazutaka Miyamoto More articles by this author Masaya Yonemori More articles by this author Akira Kurozumi More articles by this author Mayuko Kato More articles by this author Hideki Enokida More articles by this author Masayuki Nakagawa More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...