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

Nagalakshmi Nadiminty, Ramakumar Tummala, Wei Lou, Yezi Zhu, Jin Zhang, Xinbin Chen, Ralph W deVere White, Hsing-Jien Kung, Christopher P Evans, Allen C Gao

Research output: Contribution to journalArticlepeer-review

136 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1527-1537
Number of pages11
JournalJournal of Biological Chemistry
Volume287
Issue number2
DOIs
StatePublished - Jan 6 2012

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

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