MP28-12 SUPPRESSION OF ONCOGENIC MICRORNA-1274A INDUCES CELL APOPTOSIS THROUGH BMPR1B ACCELERATION IN RENAL CELL CARCINOMA

Abstract

You have accessJournal of UrologyKidney Cancer: Epidemiology & Evaluation/Staging I1 Apr 2018MP28-12 SUPPRESSION OF ONCOGENIC MICRORNA-1274A INDUCES CELL APOPTOSIS THROUGH BMPR1B ACCELERATION IN RENAL CELL CARCINOMA Hideki Enokida, Hirofumi Yoshino, Satoshi Sugita, Takashi Sakaguchi, Youichi Osako, Shuichi Tatarano, Takashi Yamane, and Masayuki Nakagawa Hideki EnokidaHideki Enokida More articles by this author , Hirofumi YoshinoHirofumi Yoshino More articles by this author , Satoshi SugitaSatoshi Sugita More articles by this author , Takashi SakaguchiTakashi Sakaguchi More articles by this author , Youichi OsakoYouichi Osako More articles by this author , Shuichi TataranoShuichi Tatarano More articles by this author , Takashi YamaneTakashi Yamane More articles by this author , and Masayuki NakagawaMasayuki Nakagawa More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2018.02.912AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES There is considerable evidence that normal microRNA (miRNA) regulatory mechanisms are disrupted in cancer cells. However, the regulatory mechanisms by which upregulated miRNAs exert their effects has not been often understood compared to downregulated miRNAs. Our previous studies of the miRNA expression signature in renal cell carcinoma (RCC) indicated that miR-1274a was significantly upregulated in clinical specimens, suggesting that miR-1274a might act as an oncogenic miRNA in RCC. The aim of this study was to investigate the functional roles of miR-1274a and identify downstream tumor suppressive targets regulated by miR-1274a in RCC cells. METHODS Expression levels of miR-1274a and its target gene were determined by qRT-PCR. Functional studies of miR-1274a were carried out by anti-miRNA to investigate cell proliferation and apoptosis by using A498, ACHN, and Caki1 RCC cell lines. Putative target genes were determined by in-silico analyses with Gene Expression Omnibus (GEO) database and the microarray study of miR-1274a-transfected ACHN. In addition, statistical analyses were performed based on the TCGA database of RCC patients. RESULTS The expression levels of miR-1274a were significantly upregulated in RCC in comparison with normal kidneys (P < 0.0001). Suppression of miR-1274a significantly inhibited cell proliferation and induced apoptosis in RCC cells (P < 0.0001 and P < 0.05, respectively). In-silico analysis of the gene expression data and luciferase reporter assays demonstrated that miR-1274a directly regulated bone morphogenetic protein receptor type 1B (BMPR1B), a member of BMP receptor family of transmembrane serine/threonine kinases. It is known that the ligands of this receptor BMPs, members of the TGF-beta superfamily, bind their receptor including BMPR1B, which lead to apoptosis thorough activation of the SMAD-dependent pathway subsequently through phosphorylation of SMAD1/5/8. Moreover, TCGA database as well as the immunohistochemistry showed that low expression of BMPR1B was observed in RCC clinical specimens compared to normal kidneys (P < 0.0001 and P = 0.0015, respectively). CONCLUSIONS We conclude that loss of oncogenic miR-1274a reduced cancer cell proliferation and induced apoptosis in RCC through targeting tumor suppressive BMPR1B. Our data demonstrating molecular pathways and a target gene regulated by oncogenic miR-1274a will provide new insight into the potential mechanisms of RCC oncogenesis. © 2018FiguresReferencesRelatedDetails Volume 199Issue 4SApril 2018Page: e361 Advertisement Copyright & Permissions© 2018MetricsAuthor Information Hideki Enokida More articles by this author Hirofumi Yoshino More articles by this author Satoshi Sugita More articles by this author Takashi Sakaguchi More articles by this author Youichi Osako More articles by this author Shuichi Tatarano More articles by this author Takashi Yamane More articles by this author Masayuki Nakagawa More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...