1061 SPLICING FACTOR ARGININE/SERINE-RICH 9 (SRSF9/SRP30C) A NOVEL ANTI-APOPTOTIC GENE REGULATED BY TUMOR SUPPRESSIVE MICRORNA-1 IN BLADDER CANCER

Abstract

You have accessJournal of UrologyBladder Cancer: Basic Research III1 Apr 20121061 SPLICING FACTOR ARGININE/SERINE-RICH 9 (SRSF9/SRP30C) A NOVEL ANTI-APOPTOTIC GENE REGULATED BY TUMOR SUPPRESSIVE MICRORNA-1 IN BLADDER CANCER Hirofumi Yoshino, Hideki Enokida, Hideo Hidaka, Takeshi Yamasaki, Shuichi Tatarano, 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 , Hideo HidakaHideo Hidaka Kagoshima, Japan More articles by this author , Takeshi YamasakiTakeshi Yamasaki Kagoshima, Japan More articles by this author , Shuichi TataranoShuichi Tatarano 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.2012.02.1167AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Growing evidences suggested that microRNAs (miRNAs) contribute to the initiation, development and metastasis of various types of cancer. Some lower expressed miRNAs could function as tumor suppressors by negatively regulating oncogenes. Based on this point, we identified several down-regulated miRNAs by our expression signatures including bladder cancer (BC) (Int J Cancer;125:345-352,2009, Int J Cancer;127:2804-2814,2010, Br J Cancer;104:808-818,2011, Br J Cancer; 105:833-841,2011). Recent our data suggested that microRNA-1 (miR-1) was significantly reduced in BC cells and restoration of the miRNA induced apoptosis in BC cells. At present, molecular mechanisms of miR-1 induced apoptotic pathways not fully understood. In this study, we identified novel apoptotic pathways regulated tumor suppressive miR-1 in BC cells. METHODS Genome-wide gene expression analysis was performed to identify the molecular networks of miR-1 by microarray technique. A luciferase reporter assay was used to identify the actual binding site between miR-1 and its candidate target genes. Cell proliferation, migration, invasion and apoptosis assays were performed to investigate the functional significance of miR-1 and its target genes in BC cell lines. RESULTS Genome-wide molecular targets search reveled that splicing factor arginine/serine-rich 9 (SRSF9/SRp30c) was down-regulated gene in miR-1 trasfectants. We focused on this gene because recent study reported that increased levels of SRSF9/SRp30c protein may facilitate the production of the anti-apoptotic Bcl-xL isoform. A luciferase reporter assay showed that SRSF9/SRp30c was directly regulated by miR-1. In clinical BC specimens, the expression level of SRSF9/SRp30c mRNA was significantly higher than that in normal epithelium (P<0.0188). Loss-of-function assays demonstrated significant inhibitions of cell proliferation, migration, and invasion in si-SRSF9/SRp30c transfectans (P<0.0001). Apoptosis assays demonstrated that the fraction of apoptotic cells increased and that caspase-3/7 was activated in miR-1 and si-SRSF9/SRp30c transfectants compared with control transfectants (each P<0.05). CONCLUSIONS SRSF9/SRp30c was directly regulated by tumor suppressive miR-1. This gene may function as oncogene and contributed to cell proliferation and apoptosis in BC. Tumor suppressive miR-1 and its target oncogene may provide new insights into the molecular pathways in BC oncogenesis. © 2012 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 187Issue 4SApril 2012Page: e430 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 Hideo Hidaka Kagoshima, Japan More articles by this author Takeshi Yamasaki Kagoshima, Japan More articles by this author Shuichi Tatarano 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 ...