1285 REGULATORY ROLE OF MIR-203 IN PROSTATE CANCER PROGRESSION AND METASTASIS

Abstract

You have accessJournal of UrologyProstate Cancer: Basic Research1 Apr 20111285 REGULATORY ROLE OF MIR-203 IN PROSTATE CANCER PROGRESSION AND METASTASIS Sharanjot Saini, Shahana Majid, Soichiro Yamamura, Z. Laura Tabatabai, Varahram Shahryari, Guoren Deng, Yuichiro Tanaka, Peter R. Carroll, and Rajvir Dahiya Sharanjot SainiSharanjot Saini San Francisco, CA More articles by this author , Shahana MajidShahana Majid San Francisco, CA More articles by this author , Soichiro YamamuraSoichiro Yamamura San Francisco, CA More articles by this author , Z. Laura TabatabaiZ. Laura Tabatabai San Francisco, CA More articles by this author , Varahram ShahryariVarahram Shahryari San Francisco, CA More articles by this author , Guoren DengGuoren Deng San Francisco, CA More articles by this author , Yuichiro TanakaYuichiro Tanaka San Francisco, CA More articles by this author , Peter R. CarrollPeter R. Carroll San Francisco, CA More articles by this author , and Rajvir DahiyaRajvir Dahiya San Francisco, CA More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2011.02.971AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES MicroRNAs (miRNAs) constitute an evolutionarily conserved class of small RNAs that suppress gene expression posttranscriptionally via sequence-specific interactions with the 3'- untranslated regions of cognate mRNA targets. Dysregulation of miRNA expression has been identified in various cancers. Accumulating data suggests that miRNAs may function as classical oncogenes, tumor suppressor genes or play a role in metastasis of various cancers. Advanced metastatic prostate cancer is a fatal disease, with only palliative therapeutic options. Advanced prostate cancer is mostly associated with bone metastatic dissemination. Though almost 80% of metastatic prostate cancer cases present bone metastasis, our current understanding of the molecular mechanisms that govern this metastatic dissemination remains fragmentary. Understanding molecular controls that signal prostate cancer progression and metastasis is important in developing better therapeutic and diagnostic interventions for the disease. The main objective of the present study was to identify microRNA genes that regulate metastatic prostate cancer. METHODS MicroRNA expression profiling was done in human prostate cell lines to identify dysregulated microRNA components of advanced prostate cancer. miR-203 expression was assessed in prostate carcinoma cell lines and clinical specimens by quantitative real-time PCR and in situ hybridization. To assess the biological significance of miR-203, miR-203 was reexpressed in bone metastatic prostate cancer cell lines followed by in vitro and in vivo functional assays. RESULTS miR-203 expression is specifically attenuated in bone metastatic prostate cancer suggesting a fundamental anti-metastatic role for this miRNA. Reintroduction of miR-203 in bone metastatic prostate cancer cell lines suppressed metastasis via inhibition of several critical steps of the metastatic cascade including epithelial-mesenchymal transition, invasion and motility. Ectopic miR-203 significantly attenuated the development of metastasis in a bone metastatic model of prostate cancer. Importantly, miR-203 regulated a cohort of pro-metastatic genes including ZEB2, Bmi (polycomb repressor), Survivin and bone specific effectors including Runx2, a master regulator of bone metastasis. CONCLUSIONS miR-203 is an ‘anti-metastatic' microRNA in prostate cancer that acts at multiple steps of the prostate cancer metastatic cascade via repression of a cohort of prometastatic targets. miR-203 may be an attractive target for therapeutic intervention in advanced prostate cancer. © 2011 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 185Issue 4SApril 2011Page: e514 Advertisement Copyright & Permissions© 2011 by American Urological Association Education and Research, Inc.MetricsAuthor Information Sharanjot Saini San Francisco, CA More articles by this author Shahana Majid San Francisco, CA More articles by this author Soichiro Yamamura San Francisco, CA More articles by this author Z. Laura Tabatabai San Francisco, CA More articles by this author Varahram Shahryari San Francisco, CA More articles by this author Guoren Deng San Francisco, CA More articles by this author Yuichiro Tanaka San Francisco, CA More articles by this author Peter R. Carroll San Francisco, CA More articles by this author Rajvir Dahiya San Francisco, CA More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...