title: miR 488* inhibits androgen receptor expression in prostate carcinoma cells.
abstract: Androgen receptor (AR) is a ligand-dependent transcription factor, which plays a significant role in prostate carcinogenesis. Blockade of AR and its ligand, androgen is the basis for the treatment of prostate cancer (PCa). Nevertheless, a modest increase in the critical levels of AR mRNA and corresponding protein is sufficient for the development of resistance to antiandrogen therapy. A strategy to further downregulate AR mRNA and protein expression in combination with antiandrogen therapy may prevent or delay the development of androgen-independent PCa. Recent studies show that microRNAs (miRNAs) perform tumor suppressor functions in various cancers. In this study, we demonstrate that the overexpression of miR 488* downregulates the transcriptional activity of AR and inhibits the endogenous AR protein production in both androgen-dependent and androgen-independent PCa cells. In addition, miR 488* blocks the proliferation and enhances the apoptosis of PCa cells. Our data indicate that miR 488* targets AR and is a potential modulator of AR mediated signaling. Our findings provide insight for utilizing miRNAs as novel therapeutics to target AR in PCa.
authors.affiliation: Center for Gene Regulation in Health and Disease, Cleveland State University, 2121 Euclid Avenue, Cleveland, OH, USA.
authors.forename: Kavleen
authors.initials: K
authors.lastname: Sikand
authors.forename: Jinani E
authors.initials: JE
authors.lastname: Slaibi
authors.forename: Rajesh
authors.initials: R
authors.lastname: Singh
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Slane
authors.forename: Girish C
authors.initials: GC
authors.lastname: Shukla
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D017209:Apoptosis; D049109:Cell Proliferation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics; D011944:Receptors, Androgen / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D014407:Tumor Cells, Cultured
chemical_list: D020413:3' Untranslated Regions; C410798:AR protein, human; C561403:MIRN488 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; D011944:Receptors, Androgen