MP46-17 TARGETING MULTIPLE FUNCTIONS OF E3 UBIQUITIN LIGASE-1 (WWP1) SIGNALING BY MIR-452 INHIBITS CANCER CELL MIGRATION AND INVASION IN PROSTATE CANCER

Abstract

You have accessJournal of UrologyProstate Cancer: Basic Research II1 Apr 2015MP46-17 TARGETING MULTIPLE FUNCTIONS OF E3 UBIQUITIN LIGASE-1 (WWP1) SIGNALING BY MIR-452 INHIBITS CANCER CELL MIGRATION AND INVASION IN PROSTATE CANCER Yusuke Goto, Akira Kurozumi, Rika Nishikawa, Mayuko Kato, Shinichi Sakamoto, Satoko Kojima, Yukio Naya, Hideki Enokida, Masayuki Nakagawa, Tomohiko Ichikawa, and Naohiko Seki Yusuke GotoYusuke Goto More articles by this author , Akira KurozumiAkira Kurozumi More articles by this author , Rika NishikawaRika Nishikawa More articles by this author , Mayuko KatoMayuko Kato More articles by this author , Shinichi SakamotoShinichi Sakamoto More articles by this author , Satoko KojimaSatoko Kojima More articles by this author , Yukio NayaYukio Naya More articles by this author , Hideki EnokidaHideki Enokida More articles by this author , Masayuki NakagawaMasayuki Nakagawa More articles by this author , Tomohiko IchikawaTomohiko Ichikawa More articles by this author , and Naohiko SekiNaohiko Seki More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.1580AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES MicroRNAs (miRNAs), a class of small noncoding RNAs, regulate protein-coding gene expression by repressing translation or cleaving RNA transcripts in a sequence-specific manner. A growing body of evidence suggests that miRNAs contribute to prostate cancer (PCa) progression, development, and metastasis. Our recent study revealed that miR-224 functions as a tumor suppressor, especially contributes to cancer cell metastasis directly targeting miR-224-TPD52 signaling (FEBS Letters, 588:1973-82, 2014). In human genome, miR-452 is located nearby tumor-suppressive miR-224, forming clustered miRNAs on chromosome Xq28 region. The aim of the study was to investigate the functional significance of miR-452 and to identify novel miR-452-mediated cancer pathways and responsible genes in PCa cells. METHODS Expression levels of miR-452 and its candidate target genes were evaluated in PCa cell lines (PC3 and DU145) and PCa clinical specimens (29 prostate tissues and 54 PCa tissues) by PCR methods. Gain-of-function studies using mature miR-452 was performed to investigate cell proliferation, migration and invasion in PCa cell lines (PC3 and DU145). To identify the molecular pathways potentially regulated by miR-452, we applied gene expression data and in silico analysis using TargetScan database [http://www.targetscan.org/] and publicly available gene expression data set in GEO. Loss-of-function assays were performed to investigate the functional significance of miR-452 target genes. RESULTS The expression level of miR-452 was significantly lower in PCa tissues and cell lines compared to normal tissues (P < 0.0001). Low expression of miR-452 was associated with shorter progression-free interval (P = 0.0414). Restoration of miR-452 in PCa cell lines revealed significant inhibition of cancer cell migration and invasion. In silico analysis and oligomicroarray analysis showed that WW domain-containing E3 ubiquitin ligase-1 (WWP1) was candidate target of miR-452 regulation. Silencing of WWP1 significantly inhibited cancer cell proliferation, migration and invasion. Up-regulation of WWP1 was detected in PCa specimens. CONCLUSIONS Down-regulation of miR-452 activates WWP1 signaling in PCa cells and these events contribute to PCa oncogenesis and metastasis. WWP1 signaling plays a variety of cellular biological processes and important roles in cancer cells. Therefore, recognition of tumor suppressive miRNA-mediated PCa pathways provides new therapeutic strategies for the disease. © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e550 Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information Yusuke Goto More articles by this author Akira Kurozumi More articles by this author Rika Nishikawa More articles by this author Mayuko Kato More articles by this author Shinichi Sakamoto More articles by this author Satoko Kojima More articles by this author Yukio Naya More articles by this author Hideki Enokida More articles by this author Masayuki Nakagawa More articles by this author Tomohiko Ichikawa More articles by this author Naohiko Seki More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...