MicroRNA Let-7c Suppresses Androgen Receptor Expression and Activity Via Regulation of Myc Expression in Prostate Cancer Cells

Overview

Journal J Biol Chem

Specialty Biochemistry

Date 2011 Dec 1

PMID 22128178

Citations 104

Authors

Nagalakshmi Nadiminty

Ramakumar Tummala

Wei Lou

Yezi Zhu

Jin Zhang

Xinbin Chen

Ralph W eVere White

Hsing-Jien Kung

Christopher P Evans

Allen C Gao

Affiliations

Soon will be listed here.

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.

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