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• W2090622338 abstract "You have accessJournal of UrologyProstate Cancer: Basic Research (III)1 Apr 2013504 MICRORNA-124 SUPPRESSES PROSTATE TUMOR GROWTH BY DOWN-REGULATING THE EXPRESSION OF ANDROGEN RECEPTORS AND THEIR ALTERNATIVE SPLICE VARIANTS IN CWR22-RV1 IN-VIVO MODEL Hao G. Nguyen, Xu-Bao Shi, Lingru Xue, Joy C. Yang, Allen C. Gao, Christopher P. Evans, and Ralph W. DeVere White Hao G. NguyenHao G. Nguyen Sacramento, CA More articles by this author , Xu-Bao ShiXu-Bao Shi Sacramento, CA More articles by this author , Lingru XueLingru Xue Sacramento, CA More articles by this author , Joy C. YangJoy C. Yang Sacramento, CA More articles by this author , Allen C. GaoAllen C. Gao Sacramento, CA More articles by this author , Christopher P. EvansChristopher P. Evans Sacramento, CA More articles by this author , and Ralph W. DeVere WhiteRalph W. DeVere White Sacramento, CA More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2013.02.1898AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The androgen receptor (AR) and its spliced variants play a central role in the progression to castrate-resistant prostate cancer (CRPC). The unique ability of microRNA to modulate the expression of genes important to prostate cancer progression can be exploited for therapeutic intervention. We hypothesize that microRNA-124 (miR124), unlike the androgen receptor signaling inhibitors (Enzalutamide and Biclutamide), targets both AR and it's alternatively splice variant V7 (AR-V7) in CWR22-Rv1 cells, thus delaying the development of CRPC. METHODS miR124 was introduced into CWR22-Rv1 cells transiently using Lipofectamine 2000 and stably using lenti-virus system. To determine the expression of AR and AR-V7, we used Western Blot analysis with specific antibodies to full-length AR and the variant. Real-time quantitative PCR was employed to evaluate the mRNA level of AR and alternate spliced variants AR-V1, AR-V3, AR-V4, and AR-V7. Xenograft mouse model using subcutaneous injection with CWR22-Rv1 cells stably over-expressing miR-124 was used to evaluate the effect of miR124 on tumor growth in-vivo. RESULTS miR124 was identified as key regulators of AR spliced variants AR-V7 and AR-V3. We showed that miR124 significantly down-regulated the expression of AR-V7 at the post-translational level (P=0.001) and AR-V3 at the post-transcriptional level. It modestly down-regulated full-length AR expression in addition to suppressing the AR signaling targets, including the anti-apoptosis protein Survivin. Xenograft tumors with enhanced expression of miR124 showed significant reduced levels of both full-length AR and AR-V7, resulting in reduced tumor growth (P=0.001). CONCLUSIONS Our study demonstrated, in the pre-clinical setting, the novel finding that miR124 significantly suppresses the full length AR expression and its alternative spliced variants, AR-V7 and AR-V3 and their downstream targets. Thus, miR124 is a potential therapeutic opportunity to delay the development of CRPC in patients treated with Enzalutamide. We have shown that miRNA 124 can be delivered systematically, a prerequisite for its clinical use. © 2013 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 189Issue 4SApril 2013Page: e206-e207 Advertisement Copyright & Permissions© 2013 by American Urological Association Education and Research, Inc.MetricsAuthor Information Hao G. Nguyen Sacramento, CA More articles by this author Xu-Bao Shi Sacramento, CA More articles by this author Lingru Xue Sacramento, CA More articles by this author Joy C. Yang Sacramento, CA More articles by this author Allen C. Gao Sacramento, CA More articles by this author Christopher P. Evans Sacramento, CA More articles by this author Ralph W. DeVere White Sacramento, CA More articles by this author Expand All Advertisement Advertisement PDF DownloadLoading ..." @default.
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• W2090622338 title "504 MICRORNA-124 SUPPRESSES PROSTATE TUMOR GROWTH BY DOWN-REGULATING THE EXPRESSION OF ANDROGEN RECEPTORS AND THEIR ALTERNATIVE SPLICE VARIANTS IN CWR22-RV1 IN-VIVO MODEL" @default.
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