MP84-08 PROTEIN ARGININE METHYLTRANSFERASE 5 IS A NOVEL EPIGENETIC REGULATOR OF ANDROGEN RECEPTOR IN PROSTATE CANCER

You have accessJournal of UrologyProstate Cancer: Basic Research & Pathophysiology III1 Apr 2016MP84-08 PROTEIN ARGININE METHYLTRANSFERASE 5 IS A NOVEL EPIGENETIC REGULATOR OF ANDROGEN RECEPTOR IN PROSTATE CANCER Xuehong Deng, Genbao Shao, Huantian Zhang, Jiaoti Huang, and Chang-Deng Hu Xuehong DengXuehong Deng More articles by this author , Genbao ShaoGenbao Shao More articles by this author , Huantian ZhangHuantian Zhang More articles by this author , Jiaoti HuangJiaoti Huang More articles by this author , and Chang-Deng HuChang-Deng Hu More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.2232AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Protein arginine methyltransferase 5 (PRMT5) is an emerging epigenetic enzyme that regulates many cellular processes by epigenetic control of target gene expression. Several reports showed that PRMT5 is overexpressed in several human cancers and that its overexpression appears to promote cancer cell growth. The objective of this study is to determine the role of PRMT5 in regulation of prostate cancer cell proliferation in vitro and tumor growth in mice. METHODS Immunohistochemistry was used to determine the expression level of PRMT5 in prostate cancer tissues. Short hairpin RNA (shRNA) was used to knock down PRMT5. Western blotting and real-time PCR were used to determine the expression level of PRMT5 in prostate cancer cells at the protein and mRNA levels. To determine how PRMT5 regulates AR expression, luciferase reporter gene, chromatin immunoprecipitation (ChIP), coimmunoprecipitation (Co-IP) and bimolecular fluorescence complementation (BiFC) assays were used. RESULTS To determine whether PRMT5 regulates prostate cancer cell proliferation, we knocked down PRMT5 by shRNA in multiple prostate cancer cell lines, and observed that PRMT5 regulates prostate cancer cell proliferation in an AR-dependent manner in both hormone naïve and castration-resistant prostate cancer cells. Molecular analyses revealed that PRMT5 interacts with the transcription factor SP1 on the AR promoter and epigenetically regulates AR transcription. Significantly, PRMT5 is overexpressed in prostate cancer tissues when compared with benign prostatic hypertrophy, and its expression positively correlates with AR expression in these tissues. Remarkably, knockdown of PRMT5 in LNCaP prostate cancer cells completely suppresses xenograft tumor growth in mice. CONCLUSIONS We have demonstrated that PRMT5 is a novel epigenetic regulator of AR in prostate cancer cells. Given that AR is the driving force of prostate cancer development and progression, our results suggest that targeting PRMT5 may be explored as a novel therapeutic approach via inhibition or elimination of AR expression. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e1092 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Xuehong Deng More articles by this author Genbao Shao More articles by this author Huantian Zhang More articles by this author Jiaoti Huang More articles by this author Chang-Deng Hu More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...