MP41-16 THE FUNCTIONAL SIGNIFICANCE AND ITS REGULATED MOLECULAR TARGETS OF MICRORNA-23B/27B/24-1 CLUSTER IN PROSTATE CANCER

Abstract

You have accessJournal of UrologyProstate Cancer: Basic Research III1 Apr 2014MP41-16 THE FUNCTIONAL SIGNIFICANCE AND ITS REGULATED MOLECULAR TARGETS OF MICRORNA-23B/27B/24-1 CLUSTER IN PROSTATE CANCER Yusuke Goto, Rika Nishikawa, Satoko Kojima, Shinichi Sakamoto, Koji Kawamura, Takashi Imamoto, Takeshi Chiyomaru, Hideki Enokida, Takashi Kinoshita, Yukio Naya, Masayuki Nakagawa, Tomohiko Ichikawa, and Naohiko Seki Yusuke GotoYusuke Goto More articles by this author , Rika NishikawaRika Nishikawa More articles by this author , Satoko KojimaSatoko Kojima More articles by this author , Shinichi SakamotoShinichi Sakamoto More articles by this author , Koji KawamuraKoji Kawamura More articles by this author , Takashi ImamotoTakashi Imamoto More articles by this author , Takeshi ChiyomaruTakeshi Chiyomaru More articles by this author , Hideki EnokidaHideki Enokida More articles by this author , Takashi KinoshitaTakashi Kinoshita More articles by this author , Yukio NayaYukio Naya 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.2014.02.1233AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail Introduction and Objectives The discovery of noncoding RNAs (ncRNAs) in the human genome was an important conceptual breakthrough in the post-genome sequencing era. MicroRNAs (miRNAs) are endogenous small ncRNA molecules (19–22 bases in length) that regulate protein-coding gene expression by repressing translation or cleaving RNA transcripts in a sequence-specific manner. Growing body evidences indicate that miRNAs deeply contribute to cancer development, progression and metastasis. In human genome, several miRNAs closely located on the same chromosomal regions, called clustered miRNAs. However, these clustered miRNAs functions are still unclear. Our miRNA expression signature of prostate cancer (PCa) showed that miR-23b/27b/24-1 clustered miRNAs were significantly downregulated in PCa. The aim of the present study was to investigate the functional significance of the miR-23b/27b/24-1 cluster and to identify the molecular targets regulated by this cluster in PCa cells. Methods Gain-of-function studies using mature miRNAs were performed to investigate cell proliferation, migration and invasion in PCa cell lines. To identify the molecular targets potentially regulated by the miR-23b/27b/24-1 cluster, we applied gene expression data and in silico analysis using TargetScan database [http://www.targetscan.org/] and GENECODIS software. Loss-of-function assays were performed to investigate the functional significance of miR-23b/27b/24-1 cluster target genes. Results Restoration of miR-23b, miR-27b and miR-24-1 in PCa cell lines revealed that these miRNAs significantly inhibited cancer cell migration and invasion. Gene expression data and in silico analysis demonstrated that golgi membrane protein 1 (GOLM1) was regulated by these clustered miRNAs. Silencing of the target gene resulted in significant inhibition of cell proliferation, migration and invasion in PCa cells. Conclusions The miR-23b/27b/24-1 clusterd miRNAs were frequently down-regulated and function as tumor suppressors in PCa. Elucidation of the molecular targets regulated by the tumor-suppressive clustered miRNAs will provide new insights into the potential molecular mechanisms of PCa oncogenesis and metastasis and will facilitate the development of novel therapeutic strategies for the treatment of PCa. © 2014FiguresReferencesRelatedDetails Volume 191Issue 4SApril 2014Page: e456-e457 Advertisement Copyright & Permissions© 2014MetricsAuthor Information Yusuke Goto More articles by this author Rika Nishikawa More articles by this author Satoko Kojima More articles by this author Shinichi Sakamoto More articles by this author Koji Kawamura More articles by this author Takashi Imamoto More articles by this author Takeshi Chiyomaru More articles by this author Hideki Enokida More articles by this author Takashi Kinoshita More articles by this author Yukio Naya 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 ...