MicroRNA let-7c suppresses androgen receptor expression and activity via regulation of Myc expression in prostate cancer cells.

Authors: Nadiminty N; Tummala R; Lou W; Zhu Y; Zhang J; Chen X; eVere White RW; Kung HJ; Evans CP; Gao AC

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.

Keywords: Cell Line, Tumor; Cell Proliferation; *Gene Expression Regulation, Neoplastic; Humans; Male; MicroRNAs/*biosynthesis/genetics; Prostatic Neoplasms/genetics/*metabolism; Proto-Oncogene Proteins c-myc/genetics/*metabolism; RNA, Neoplasm/*biosynthesis/genetics; RNA-Binding Proteins/genetics/metabolism; Receptors, Androgen/*biosynthesis/genetics; Signal Transduction/genetics
Journal: The Journal of biological chemistry
Volume: 287
Issue: 2
Pages: 1527-37
Date: Dec. 1, 2011
PMID: 22128178
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Citation:

Nadiminty N, Tummala R, Lou W, Zhu Y, Zhang J, Chen X, eVere White RW, Kung HJ, Evans CP, Gao AC (2012) MicroRNA let-7c suppresses androgen receptor expression and activity via regulation of Myc expression in prostate cancer cells. The Journal of biological chemistry 287: 1527-37.


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  • hsa-let-7c microRNA let-7c


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