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

N. Nadiminty, R. Tummala, W. Lou, Y. Zhu, J. Zhang, X. Chen, R.W. DeVere White, H.-J. Kung, C.P. Evans, A.C. Gao

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144 引文 斯高帕斯(Scopus)

摘要

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. © 2012 by The American Society for Biochemistry and Molecular Biology, Inc.
原文英語
頁(從 - 到)1527-1537
頁數11
期刊Journal of Biological Chemistry
287
發行號2
DOIs
出版狀態已發佈 - 一月 2012
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