title: MicroRNA let-7c suppresses androgen receptor expression and activity via regulation of Myc expression in prostate cancer cells.
abstract: Castration-resistant prostate cancer continues to rely on androgen receptor (AR) expression. AR plays a central role in the development of prostate cancer and progression to castration resistance during and after androgen deprivation therapy. Here, we identified miR-let-7c as a key regulator of expression of AR. miR-let-7c suppresses AR expression and activity in human prostate cancer cells by targeting its transcription via c-Myc. Suppression of AR by let-7c leads to decreased cell proliferation of human prostate cancer cells. Down-regulation of Let-7c in prostate cancer specimens is inversely correlated with AR expression, whereas the expression of Lin28 (a repressor of let-7) is correlated positively with AR expression. Our study demonstrates that the miRNA let-7c plays an important role in the regulation of androgen signaling in prostate cancer by down-regulating AR expression. These results suggest that reconstitution of miR-let-7c may aid in targeting enhanced and hypersensitive AR in advanced prostate cancer.
authors: Department of Urology, University of California at Davis, Sacramento, California 95817, USA. nnadiminty@ucdavis.edu
authors: Nagalakshmi
authors: N
authors: Nadiminty
authors: Ramakumar
authors: R
authors: Tummala
authors: Wei
authors: W
authors: Lou
authors: Yezi
authors: Y
authors: Zhu
authors: Jin
authors: J
authors: Zhang
authors: Xinbin
authors: X
authors: Chen
authors: Ralph W
authors: RW
authors: eVere White
authors: Hsing-Jien
authors: HJ
authors: Kung
authors: Christopher P
authors: CP
authors: Evans
authors: Allen C
authors: AC
authors: Gao
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism*; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism*; D012334:RNA, Neoplasm / Q000096:biosynthesis* / Q000235:genetics; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D011944:Receptors, Androgen / Q000096:biosynthesis* / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics
chemical_list: C000715187:Lin28A protein, human; C489427:MYC protein, human; D035683:MicroRNAs; D016271:Proto-Oncogene Proteins c-myc; D012334:RNA, Neoplasm; D016601:RNA-Binding Proteins; D011944:Receptors, Androgen; C487931:mirnlet7 microRNA, human