title: Androgen receptor is negatively correlated with the methylation-mediated transcriptional repression of miR-375 in human prostate cancer cells.
abstract: Androgen receptor (AR) plays a critical role during the development and progression of prostate cancer in which microRNA miR-375 is overexpressed and correlated with tumor progression. Although DNA methylation is a key mechanism for the repression of gene expression, the relationship between AR and the expression or the hypermethylation of miR-375 is unknown. In this study, we found that AR-positive prostate cancer (PCa) cells showed high expression levels and hypomethylation of the miR-375. In contrast, AR-negative PCa cells displayed low levels and hypermethylation of the miR-375. Addition of 5-Aza-2'-deoxycytidine, a specific inhibitor of DNA methylation, into the culture medium reversed the low expression levels of miR-375 in the AR negative PCa cells. In addition, the total activity levels of DNA methyltransferases (DNMTs) were high in AR-negative PCa cells, in which hypermethylation of miR-375 promoter and low expression levels of miR-375 were observed. Taken together, these findings indicate that the negative correlation between AR and total DNMT activity is one of mechanisms to influence the methylation status of miR-375 promoter, which in turn regulates the expression of miR-375.
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Stem Cell Research Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, P.R. China.
authors.forename: Mingliang
authors.initials: M
authors.lastname: Chu
authors.forename: Yunli
authors.initials: Y
authors.lastname: Chang
authors.forename: Ping
authors.initials: P
authors.lastname: Li
authors.forename: Yanjing
authors.initials: Y
authors.lastname: Guo
authors.forename: Kaiqing
authors.initials: K
authors.lastname: Zhang
authors.forename: Weiqiang
authors.initials: W
authors.lastname: Gao
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D045744:Cell Line, Tumor; D019175:DNA Methylation / Q000235:genetics*; D015254:DNA Modification Methylases / Q000096:biosynthesis; D000077209:Decitabine; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics; D011471:Prostatic Neoplasms / Q000235:genetics*; D034622:RNA Interference; D034741:RNA, Small Interfering; D011944:Receptors, Androgen / Q000235:genetics*; D015533:Transcriptional Activation / Q000235:genetics
chemical_list: C410798:AR protein, human; D000964:Antimetabolites, Antineoplastic; D004791:Enzyme Inhibitors; C540933:MIRN375 microRNA, human; D035683:MicroRNAs; D034741:RNA, Small Interfering; D011944:Receptors, Androgen; D000077209:Decitabine; D015254:DNA Modification Methylases; D001374:Azacitidine