MP23-02 THE CLUSTERED MICRORNA-23B/27B FUNCTION AS TUMOR SUPPRESSORS AND USEFUL PROGNOSTIC MARKERS IN RENAL CELL CARCINOMA

Abstract

You have accessJournal of UrologyKidney Cancer: Basic Research I1 Apr 2014MP23-02 THE CLUSTERED MICRORNA-23B/27B FUNCTION AS TUMOR SUPPRESSORS AND USEFUL PROGNOSTIC MARKERS IN RENAL CELL CARCINOMA Tomoaki Ishihara, Takeshi Chiyomaru, Satoru Inoguchi, Hideki Enokida, Naohiko Seki, and Masayuki Nakagawa Tomoaki IshiharaTomoaki Ishihara More articles by this author , Takeshi ChiyomaruTakeshi Chiyomaru More articles by this author , Satoru InoguchiSatoru Inoguchi More articles by this author , Hideki EnokidaHideki Enokida More articles by this author , Naohiko SekiNaohiko Seki More articles by this author , and Masayuki NakagawaMasayuki Nakagawa More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2014.02.870AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES A growing body of evidence suggests that microRNAs (miRNAs) play an important role in cancer diagnosis and therapy. MicroRNA-23b (miR-23b) and miR-27b are closely located on chromosome 9q22.32, so called clustered miRNAs. MiR-23b/27b cluster is down-regulated in several human malignancies. Our recent miRNA expression signature of renal cell carcinoma (RCC) revealed that miR-23b and miR-27b expression were reduced in RCC, suggesting that miR-23b/27b cluster is a candidate tumor suppressor. The aim of this study is to investigate the functional significance of miR-23b/27b cluster, and to identify its target genes in RCC. METHODS We evaluated miR-23b and miR-27b expressions in 27 RCC clinical specimens and 27 normal kidney tissues by stem-loop RT-PCR. We analyzed their correlation with clinicopathological features. Furthermore, overall survival (OS) of 27 RCC patients was evaluated using the Kaplan-Meier method. We performed gain-of-function studies (cell migration and invasion assays) by mature miRNAs transfection into RCC cell lines (A498 and 786-O). To identify the targets potentially regulated by the miR-23b/27b cluster, we applied genome-wide gene expression analysis and in silico study. RESULTS The expression of miR-23b and miR-27b was significantly reduced in the RCC specimens (respectively, P<0.0001 and P=0.0002). MiR-23b and miR-27b expression level were significantly lower in recurrence group of patients compared to no-recurrence group (P=0.0147 and P=0.0313). MiR-23b and miR-27b expression level was significantly lower in high T stage (over pT3) compared to low T stage (under pT2) (P=0.0257 and P=0.0146). MiR-23b/27b expression level was significantly lower in high grade group compared to low grade group (P=0.0019). Kaplan-Meier analysis showed that the low miR-23b/27b group had lower OS probability compared to the high miR-23b/27b group (P=0.0664). Significant inhibitions of cell migration and invasion were observed in the miR-23b and miR-27b transfectants. In silico analysis exhibited 22 putative target oncogenes of miR-23b/27b cluster. CONCLUSIONS Our data indicated that miR-23b/27b cluster functioned as pivotal suppressor of cell migration and invasion in RCC and might be a prognostic cancer biomarker. © 2014FiguresReferencesRelatedDetails Volume 191Issue 4SApril 2014Page: e243 Advertisement Copyright & Permissions© 2014MetricsAuthor Information Tomoaki Ishihara More articles by this author Takeshi Chiyomaru More articles by this author Satoru Inoguchi More articles by this author Hideki Enokida More articles by this author Naohiko Seki More articles by this author Masayuki Nakagawa More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...