MP44-14 DOWNREGULATION OF MIR-200B IS ASSOCIATED WITH CISPLATIN-RESISTANCE IN BLADDER CANCER CELLS

Abstract

You have accessJournal of UrologyBladder Cancer: Basic Research & Pathophysiology I1 Apr 2017MP44-14 DOWNREGULATION OF MIR-200B IS ASSOCIATED WITH CISPLATIN-RESISTANCE IN BLADDER CANCER CELLS Tetsuya Shindo, Naotaka Nishiyama, Takeshi Niinuma, Hiroshi Kitajima, Masahiro Kai, Takashi Tokino, Nobuo Shinkai, Hiromu Suzuki, and Naoya Masumori Tetsuya ShindoTetsuya Shindo More articles by this author , Naotaka NishiyamaNaotaka Nishiyama More articles by this author , Takeshi NiinumaTakeshi Niinuma More articles by this author , Hiroshi KitajimaHiroshi Kitajima More articles by this author , Masahiro KaiMasahiro Kai More articles by this author , Takashi TokinoTakashi Tokino More articles by this author , Nobuo ShinkaiNobuo Shinkai More articles by this author , Hiromu SuzukiHiromu Suzuki More articles by this author , and Naoya MasumoriNaoya Masumori More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.1345AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Chemoresistance to cisplatin (CDDP) is one of the major clinical issues in bladder cancer (BCa) treatment. MicroRNAs (miRNA) are noncoding RNAs that are potentially involved in chemoresistance in various cancers. We therefore aimed to determine the roles of miRNAs in the CDDP-resistance in BCa. METHODS We established 2 CDDP-resistant BCa cell lines (T24RC and EJ138RC) by continuously treating parental T24 and EJ138 cells. Profiles of miRNA expression in BCa cells were assessed by TaqMan arrays (Applied Biosystems). BCa cells were transfected with a mimic or an inhibitor of miR-200b (Ambion), after which the sensitivities to CDDP were evaluated via cell viability assays. Methylation of a CpG island of the miR200b gene was assessed by bisulfite-pyrosequencing. BCa cells were treated with the DNA demethylating agent 5-aza-2′-deoxycytidine (5-aza-dC) to restore the expression of miR-200b. RESULTS Of the 754 miRNAs analyzed, miR-200b was downregulated in CDDP-resistant BCa cells (Figure 1). Induction of miR-200b in T24RC cells restored the CDDP sensitivity (Figure 2a). In contrast, inhibition of miR-200b increased CDDP resistance in T24 and EJ138 cells (Figure 2b and 2c). The levels of methylation in the CpG islands of miR-200b were significantly increased in T24RC and EJ138RC as compared to their parental cells (T24RC, 83.3%; T24, 53.3%; EJ138RC, 77.0%; EJ138, 62.6%; P < 0.01, Student t test), and treatment with 5-aza-dC restored the miR-200b expression in resistant cells (Figure 3a and 3b). Moreover, treatment with CDDP and 5-aza-dC synergistically inhibited the growth of T24RC cells (Figure 3c). CONCLUSIONS Our results suggest that epigenetic downregulation of miR-200b may be causally related to the CDDP-resistance in BCa, and that it could be a potential therapeutic target. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e568-e569 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Tetsuya Shindo More articles by this author Naotaka Nishiyama More articles by this author Takeshi Niinuma More articles by this author Hiroshi Kitajima More articles by this author Masahiro Kai More articles by this author Takashi Tokino More articles by this author Nobuo Shinkai More articles by this author Hiromu Suzuki More articles by this author Naoya Masumori More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...