142 EMT RELATED MICRORNA-200 FAMILY FUNCTION AS TUMOR SUPPRESSORS IN RENAL CELL CARCINOMA (2012)

You have accessJournal of UrologyKidney Cancer: Basic Research I1 Apr 2012142 EMT RELATED MICRORNA-200 FAMILY FUNCTION AS TUMOR SUPPRESSORS IN RENAL CELL CARCINOMA Hirofumi Yoshino, Hideki Enokida, Takeshi Yamasaki, Hideo Hidaka, Takeshi Chiyomaru, Nijiro Nohata, Naohiko Seki, and Masayuki Nakagawa Hirofumi YoshinoHirofumi Yoshino Kagoshima, Japan More articles by this author , Hideki EnokidaHideki Enokida Kagoshima, Japan More articles by this author , Takeshi YamasakiTakeshi Yamasaki Kagoshima, Japan More articles by this author , Hideo HidakaHideo Hidaka Kagoshima, Japan More articles by this author , Takeshi ChiyomaruTakeshi Chiyomaru Kagoshima, Japan More articles by this author , Nijiro NohataNijiro Nohata Chiba, 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.2012.02.192AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Renal cell carcinoma (RCC) is the most common neoplasm of the adult kidney, and clear cell RCC represents the most common renal cancer histology. However surgical treatment is provided for localized disease, relapse or metastasis of the patient is caused in a considerable ratio. At present, metastatic RCC is difficult to treat and the process of metastasis is not well understood. Therefore, it is crucial to find molecular mechanisms based on recent genome analysis in RCC oncogenesis and metastasis. Based on the microRNA (miRNA) expression signature of RCC revealed that miR-200 family significantly reduced in RCC cells. The miR-200 family (miR-200b, miR-200a and miR-429 are encoded by single polycistronic transcript on chromosome 1p36.33 and miR-200c and miR-141 are cluster on chromosome 12 p13.31) of miRNA plays a major role to epithelial to mesenchymal transition (EMT) by targeting transcription repressors, zinc-finger E-box binding homeobox (ZEB1) and ZEB2. In this study, we investigated the functional significance of miR-200 family and identified the novel cancer pathways in RCC. METHODS Cell proliferation and invasion assay was performed by restoration of mature miR-200 family (miR-200a, miR-200b, miR-200c, miR-429 and miR-141) in RCC cell lines. Genome-wide gene expression analysis was performed to identify the molecular networks of miR-200 family by microarray analysis. RESULTS The mRNA expression levels of ZEB1 and ZEB2 were significantly decreased by miR-200 family (miR-200a, miR-200b, miR-200c, miR-429 and miR-141) transfectantion in RCC cells (P < 0.0001). Restoration of each miRNAs significantly inhibited cell proliferation and invasion in RCC cells (P < 0.0001). Interestingly, the morphological changes were recognized by miR-200 family transfection in RCC cell lines. Gene expression analysis showed more than ten candidate genes were searched for miR-200 family targets and these genes were up-regulated in RCC clinical specimens. CONCLUSIONS Our data suggest that miR-200 family function as tumor suppressors in RCC. EMT-related tumor suppressive miR-200 family mediates novel molecular targets provide new insights into the potential mechanisms of RCC oncogenesis and metastasis. © 2012 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 187Issue 4SApril 2012Page: e59 Advertisement Copyright & Permissions© 2012 by American Urological Association Education and Research, Inc.MetricsAuthor Information Hirofumi Yoshino Kagoshima, Japan More articles by this author Hideki Enokida Kagoshima, Japan More articles by this author Takeshi Yamasaki Kagoshima, Japan More articles by this author Hideo Hidaka Kagoshima, Japan More articles by this author Takeshi Chiyomaru Kagoshima, Japan More articles by this author Nijiro Nohata Chiba, 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 ...