505 MIR-218 ON THE GENOMIC LOSS REGION OF CHROMOSOME 4P15.31 FUNCTIONS AS A TUMOR SUPPRESSOR IN BLADDER CANCER (2011)

You have accessJournal of UrologyBladder Cancer: Basic Research1 Apr 2011505 MIR-218 ON THE GENOMIC LOSS REGION OF CHROMOSOME 4P15.31 FUNCTIONS AS A TUMOR SUPPRESSOR IN BLADDER CANCER Shuichi Tatarano, Takeshi Chiyomaru, Hideki Enokida, Kazumori Kawakami, Kenryu Nishiyama, Naohiko Seki, and Masayuki Nakagawa Shuichi TataranoShuichi Tatarano Kagoshima, Japan More articles by this author , Takeshi ChiyomaruTakeshi Chiyomaru Kagoshima, Japan More articles by this author , Hideki EnokidaHideki Enokida Kagoshima, Japan More articles by this author , Kazumori KawakamiKazumori Kawakami Kagoshima, Japan More articles by this author , Kenryu NishiyamaKenryu Nishiyama Kagoshima, Japan More articles by this author , Naohiko SekiNaohiko Seki Chiba, Japan More articles by this author , and Masayuki NakagawaMasayuki Nakagawa Kagoshima, Japan More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2011.02.1201AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES MicroRNAs (miRNAs) are an abundant class of small non-coding RNAs and display aberrant expression patterns and functional abnormalities in human diseases including cancers. While some miRNAs function as tumor suppressors and are down-regulated in cancer cells, other miRNAs act as oncogenes. However, genetic or epigenetic regulations of these miRNAs are not fully elucidated as of now. We hypothesize that chromosomal loss region harbors down-regulated miRNAs that have a tumor suppressive function in bladder cancer (BC). METHODS On the basis of our previous comparative genomic hybridization (CGH) array data in BC cell lines, we focused on chromosome 4 because it was the frequent genomic loss region, and 23 miRNAs were coded there. The expression levels of 19 miRNAs, whose PCR primers were commercially available, were evaluated by a real-time PCR in four BC cell lines and 22 clinical samples. The miRNA′s transfected BC cell lines (BOY and T24) were subjected to cell viability assays by cell growth, wound healing, and matrigel invasion assay; and apoptosis assay by flow cytometory. To find which genes were differentially regulated by the miRNAs, the gene expression profile of the miRNA′s transfectants was performed. RESULTS Among the 19 miRNAs on chromosome 4, the expression levels of miR-95, miR-218 and miR-578 were markedly repressed in the four BC cell lines. In clinical samples, miR-218 located on chromosome 4p15.31 was actually down-regulated in 16 clinical BC specimens in comparison with six normal bladder epitheliums (NBEs) (p = 0.0004), whereas no significant difference was observed in miR-95 and miR-578 expressions among the groups. Significant cell viability inhibitions of cell growth, invasion and migration were observed in miR-218 transfectants (each, p < 0.005). The flow cytometory demonstrated that the apoptotic fraction was significantly greater in the miR-218 transfectants than in the controls (each, p < 0.005). Oligo-microarray analyses identified that a total of 337 down-regulated genes and 162 up-regulated genes were differently expressed in the transfectants. Interestingly, anti-apoptotic TMX1 gene and signaling pathway regulator RGS20 gene, which have miR-218 conserved binding sites in their mRNA, were listed in the top 20 down-regulated genes. CONCLUSIONS Our data suggest that miR-218 may be a tumor suppressive miRNA and that its expression was generally down-regulated in BC due to the chromosomal loss region where the miRNA harbors. © 2011 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 185Issue 4SApril 2011Page: e205 Advertisement Copyright & Permissions© 2011 by American Urological Association Education and Research, Inc.MetricsAuthor Information Shuichi Tatarano Kagoshima, Japan More articles by this author Takeshi Chiyomaru Kagoshima, Japan More articles by this author Hideki Enokida Kagoshima, Japan More articles by this author Kazumori Kawakami Kagoshima, Japan More articles by this author Kenryu Nishiyama Kagoshima, Japan More articles by this author Naohiko Seki Chiba, Japan More articles by this author Masayuki Nakagawa Kagoshima, Japan More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...