557 INDUCTION OF TUMOR SUPPRESSOR GENES IL24 AND IL32 BY MICRORNA-205 IN PROSTATE CANCER (2010)

You have accessJournal of UrologyProstate Cancer: Basic Research IV1 Apr 2010557 INDUCTION OF TUMOR SUPPRESSOR GENES IL24 AND IL32 BY MICRORNA-205 IN PROSTATE CANCER Shahana Majid, Altaf Dar, Sharanjot Saini, Yi Chen, Varahram Shahryari, Jan Liu, Saif Zaman, Hiroshi Hirata, Soichiro Yamamura, Koji Ueno, Gaurav Khatri, Peter Carroll, and Rajvir Dahiya Shahana MajidShahana Majid More articles by this author , Altaf DarAltaf Dar More articles by this author , Sharanjot SainiSharanjot Saini More articles by this author , Yi ChenYi Chen More articles by this author , Varahram ShahryariVarahram Shahryari More articles by this author , Jan LiuJan Liu More articles by this author , Saif ZamanSaif Zaman More articles by this author , Hiroshi HirataHiroshi Hirata More articles by this author , Soichiro YamamuraSoichiro Yamamura More articles by this author , Koji UenoKoji Ueno More articles by this author , Gaurav KhatriGaurav Khatri 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.2010.02.777AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES MicroRNAs are small noncoding RNAs that regulate the expression of approximately 30% of all human genes, either inhibiting target mRNA translation or inducing its degradation. These genes are abnormally expressed in human malignancies, making their biological importance increasingly apparent. Given the functional complexity of miRNA mediated gene regulation, it is unlikely that miRNAs are limited to gene silencing. The main objective of this study was to investigate the involvement of miRNA-205 in prostate carcinogenesis and whether miR-205 functions as a tumor suppressor by transcriptionally up-regulating tumor suppressor genes IL24 and IL32. METHODS The methods employed in this study include quantitative-real time PCR; western blot; in-situ hybridization; fluorescence-activated cell sorting assays for cell cycle distribution and apoptosis; assays for cell viabiltity, clonability, migration and invasiveness of prostate cancer cells. Luciferase reporter and mutational assays; nuclear run-on, in-vitro transcription and chromatin immunoprecipitation assays were also performed. RESULTS Our results indicated that miR-205 expression levels are either silenced or significantly lower in prostate cancer cell lines and prostate tumors when compared to non-malignant prostate cell lines or benign prostate hyperplasia tissues respectively. By scanning gene promoters for sequences complementary to miR-205, we identified putative miR-205 target sites in the promoters of IL24 and IL32 tumor suppressor genes. Over-expression of miR-205 in prostate cancer cells (PC-3) induced the expression of both genes by targeting specific sites in their promoters. Transfection of miR-205 impaired cancer cell growth, clonability, migration, invasiveness and induced apoptosis and cell cycle arrest by interfering with the expression of genes involved in these pathways. MicroRNA-205 induced in-vitro transcription and caused enrichment of histone markers indicative of transcriptionally active promoters in IL24 and IL32 genes. Luciferase reporter and mutational assays indicated that IL24 and IL32 are the direct targets of miR-205. CONCLUSIONS For the first time we have shown that microRNA-205 specifically activates tumor suppressor genes IL24 and IL32 by targeting complimentary binding sites in their promoters, corroborating a new function for miRNAs in regulating gene transcription. Such a function of microRNAs may contribute to the novel therapeutic approach in the treatment of prostate cancer. San Francisco, CA© 2010 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 183Issue 4SApril 2010Page: e218-e219 Advertisement Copyright & Permissions© 2010 by American Urological Association Education and Research, Inc.Metrics Author Information Shahana Majid More articles by this author Altaf Dar More articles by this author Sharanjot Saini More articles by this author Yi Chen More articles by this author Varahram Shahryari More articles by this author Jan Liu More articles by this author Saif Zaman More articles by this author Hiroshi Hirata More articles by this author Soichiro Yamamura More articles by this author Koji Ueno More articles by this author Gaurav Khatri 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 ...