Abstract
You have accessJournal of UrologyBladder Cancer: Basic Research I1 Apr 2014MP21-18 TUMOR SUPPRESSIVE MICRORNA-24 INHIBITS BLADDER CANCER VIA TARGETING TRANSCRIPTION FACTOR FOXM1 Satoru Inoguchi, Takeshi Chiyomaru, Tomoaki Ishihara, Hideki Enokida, Naohiko Seki, and Masayuki Nakagawa Satoru InoguchiSatoru Inoguchi More articles by this author , Takeshi ChiyomaruTakeshi Chiyomaru More articles by this author , Tomoaki IshiharaTomoaki Ishihara 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.2014.02.846AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Our recent microRNA (miRNA) expression signature of bladder cancer (BC) revealed that miR-24 expression was significantly reduced in BC, suggesting that it may function as a tumor suppressive miRNA. The aim of this study is to investigate the functional significance of miR-24 and to identify its target genes in BC. METHODS We evaluated miR-24 expression in 58 BC clinical specimens and 25 normal bladder epithelia by real-time PCR. Overall survival (OS) of BC patients was evaluated using the Kaplan-Meier method. To investigate the functional role of miR-24, we performed gain-of-function studies (cell proliferation, apoptosis and cell cycle assay) by using miR-24 transfectants. To identify the targets regulated by miR-24, we applied genome-wide gene expression analysis and in silico study. A luciferase reporter assay was carried out to determine whether 3′UTR of FOXM1 has an actual biding site for miR-24. We investigated whether FOXM1 was regulated by miR-24 by real-time PCR and western blotting and the expression level of FOXM1 in clinical BCs and normal bladder specimens by real-time PCR. RESULTS MiR-24 expression in BC specimens was significantly lower than that in normal bladder epithelia (P<0.0001). Kaplan-Meier analysis showed that the low miR-24 group had significantly lower OS probability compared to the high miR-24 group (P=0.0339). XTT assay demonstrated that cell viability was significantly inhibited in the miR-24 transfectants compared with the control. Flow cytometry analysis showed that G2 arrest and apoptosis were induced in the miR-24 transfectants. The expression level of FOXM1 was supressed by miR-24 at protein level. Luciferase reporter assay showed that FOXM1 was directly regulated by miR-24. In clinical specimens, expression levels of FOXM1 were significantly up-regulated in BC specimens compared with the normal specimens (P<0.0001). FOXM1 expression level was significantly higher in high T stage (over pT2) compared to that in low T stage (under pT1) (P=0.0022). FOXM1 expression level was significantly higher in high grade group compared to low grade (P=0.0004). CONCLUSIONS MiR-24 was significantly down-regulated in BC clinical specimens and appeared to function as a tumor suppressor in BC through inhibition of FOXM1. The reduced expression of miR-24 may be associated with shorter OS of BC patients, suggesting that miR-24 might be a potential biomarker for prognosis prediction in the treatment of BC. © 2014FiguresReferencesRelatedDetails Volume 191Issue 4SApril 2014Page: e232-e233 Advertisement Copyright & Permissions© 2014MetricsAuthor Information Satoru Inoguchi More articles by this author Takeshi Chiyomaru More articles by this author Tomoaki Ishihara 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 ...
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