You have accessJournal of UrologyProstate Cancer: Basic Research IV1 Apr 2010542 MICRORNAS 221/222 AND GENISTEIN MEDIATED REGULATION OF ARHI TUMOR SUPPRESSOR GENE IN PROSTATE CANCER Yi Chen, Guoren Deng, Shahana Majid, Shranjot Saini, Saif Zaman, Jan Liu, Yuichiro Tanaka, Peter Carroll, and Rajvir Dahiya Yi ChenYi Chen More articles by this author , Guoren DengGuoren Deng More articles by this author , Shahana MajidShahana Majid More articles by this author , Shranjot SainiShranjot Saini More articles by this author , Saif ZamanSaif Zaman More articles by this author , Jan LiuJan Liu More articles by this author , Yuichiro TanakaYuichiro Tanaka More articles by this author , Peter CarrollPeter Carroll More articles by this author , and Rajvir DahiyaRajvir Dahiya More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2010.02.762AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES ARHI, an imprinted tumor suppressor gene, is expressed in normal immortalized prostate epithelial cells, but is dramatically down-regulated in prostate cancer cell lines. Here we investigated the mechanisms of ARHI silencing in prostate cancer through miRNA and genistein mediated pathways. METHODS We evaluated ARHI mRNA levels by real time PCR using Q-PCR slice (48 prostate tumor and normal adjacent tissues) and protein levels by immunostaining of prostate tissue array (36 cancer, 8 matched normal adjacent tissue and 4 bone metastases). Then, ARHI was over-expressed in prostate cancer PC-3 cells by introduction of ARHI plasmid followed by functional studies. At last, miRNA inhibitor studies and dual luciferase pMIR-REPORT assay has been performed to prove the direct target of miR-221&222 to ARHI. RESULTS Both ARHI mRNA and protein levels were down regulated in prostate cancer tissues compared to adjacent normal tissues. Over-expression of ARHI can inhibited cell proliferation, colony formation, invasion and induced caspase-independent apoptosis. Further studies on new mechanism of ARHI down regulation showed a significant inverse relationship between ARHI and miR-221 & 222 which were up-regulated in cancer cell line. Transfection of miR-221 & 222 inhibitors into PC-3 cells caused a significant induction of ARHI expression. A direct interaction of miR-221 or 222 with a target site on the 3'UTR of ARHI was confirmed by a dual luciferase pMIR-REPORT assay. Finally, we also found that genistein (a dietary isoflavone from soy) up-regulates ARHI by down regulating miR-221 & 222 in PC-3 cells. CONCLUSIONS ARHI is a tumor suppressor gene down regulated in prostate cancer, and over-expression of ARHI can inhibit cell proliferation, colony formation and invasion. This study demonstrates for the first time that prostate cancer cells have elevated levels of miR-221 & 222 which bind to the 3'UTR of ARHI contributing to its down regulation. Genistein, a potential non-toxic chemopreventive agent restores expression of ARHI and may be an important dietary therapeutic agent for treating prostate cancer. San Francisco, CA© 2010 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 183Issue 4SApril 2010Page: e213 Advertisement Copyright & Permissions© 2010 by American Urological Association Education and Research, Inc.MetricsAuthor Information Yi Chen More articles by this author Guoren Deng More articles by this author Shahana Majid More articles by this author Shranjot Saini More articles by this author Saif Zaman More articles by this author Jan Liu More articles by this author Yuichiro Tanaka More articles by this author Peter Carroll More articles by this author Rajvir Dahiya More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...