MP60-17 OVEREXPRESSION OF CYP1B1 MEDIATED BY LOSS OF MIR-200C PROMOTES RENAL CELL CARCINOMA TUMORIGENESIS VIA ALTERED EXPRESSIONS OF CDC20 AND DAPK1

Abstract

You have accessJournal of UrologyKidney Cancer: Basic Research & Pathophysiology II1 Apr 2017MP60-17 OVEREXPRESSION OF CYP1B1 MEDIATED BY LOSS OF MIR-200C PROMOTES RENAL CELL CARCINOMA TUMORIGENESIS VIA ALTERED EXPRESSIONS OF CDC20 AND DAPK1 Yozo Mitsui, Inik Chang, Koji Tamura, Toshihiro Tai, Masato Nagata, Fumito Yamabe, Kuri Suzuki, Hideyuki Kobayashi, Koichi Nagao, Koichi Nakajima, Rajvir Dahiya, and Yuichiro Tanaka Yozo MitsuiYozo Mitsui More articles by this author , Inik ChangInik Chang More articles by this author , Koji TamuraKoji Tamura More articles by this author , Toshihiro TaiToshihiro Tai More articles by this author , Masato NagataMasato Nagata More articles by this author , Fumito YamabeFumito Yamabe More articles by this author , Kuri SuzukiKuri Suzuki More articles by this author , Hideyuki KobayashiHideyuki Kobayashi More articles by this author , Koichi NagaoKoichi Nagao More articles by this author , Koichi NakajimaKoichi Nakajima More articles by this author , Rajvir DahiyaRajvir Dahiya More articles by this author , and Yuichiro TanakaYuichiro Tanaka More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.1854AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Cytochrome P450 1B1 (CYP1B1) has been shown to be up-regulated in many types of cancer including renal cell carcinoma (RCC), while several reports have shown that CYP1B1 influences regulation of tumor development. However, its role in RCC development has not been elucidated. Here, we explored the functional role and regulatory mechanism of CYP1B1 in RCC. METHODS CYP1B1 expression was determined in RCC cell lines, and microarray findings of 96 RCC and 25 normal tissues were obtained. To examine the biological significance of CYP1B1 in RCC progression, we silenced the gene in Caki-1 and 769-P cells by RNA interference, and performed various functional analyses. Furthermore, we evaluated whether miR-200c expression, significantly down-regulated in RCC, is associated with CYP1B1 level in both clinical samples and cell lines. RESULTS First, we confirmed that CYP1B1 protein expression was significantly higher in RCC cell lines as compared to normal kidney tissues, a trend that was also observed in RCC tumor samples (p<0.01). Furthermore, CYP1B1 expression was associated with tumor grade and stage. Next, we silenced the gene in Caki-1 and 769-P cells by RNA interference, and performed various functional analyses to determine the biological significance of CYP1B1 in RCC progression. Inhibition of CYP1B1 expression resulted in decreased cell proliferation, and migration and invasion of RCC cells, while that also induced apoptosis of Caki-1 cells. In addition, gene microarray findings indicated that the anti-tumor effects on RCC cells caused by CYP1B1 depletion might have been due to alteration of CDC20 and DAPK1 expressions, which was confirmed by real-time PCR. Interestingly, CYP1B1 expression was associated with CDC20 and DAPK1 expressions in the clinical samples. Finally, we found that CYP1B1 level was inversely correlated with miR-200c expression in RCC, and miR-200c directly targets the CYP1B1 3′-UTR and regulates its expression. CONCLUSIONS CYP1B1 up-regulation mediated by reduced expression of miR-200C may promote RCC development by inducing CDC20 expression and inhibiting apoptosis via down-regulation of DAPK1. Our results demonstrate that CYP1B1 and miR-200c are potential tumor biomarkers and targets for anticancer therapy in RCC patients. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e796 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Yozo Mitsui More articles by this author Inik Chang More articles by this author Koji Tamura More articles by this author Toshihiro Tai More articles by this author Masato Nagata More articles by this author Fumito Yamabe More articles by this author Kuri Suzuki More articles by this author Hideyuki Kobayashi More articles by this author Koichi Nagao More articles by this author Koichi Nakajima More articles by this author Rajvir Dahiya More articles by this author Yuichiro Tanaka More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...