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

作者：Nadiminty Nagalakshmi^*; Tummala Ramakumar; Lou Wei; Zhu Yezi; Zhang Jin; Chen Xinbin; White Ralph W deVere; Kung Hsing Jien; Evans Christopher P; Gao Allen C

来源：JOURNAL OF BIOLOGICAL CHEMISTRY, 2012, 287(2): 1527-1537.

DOI：10.1074/jbc.M111.278705

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.

• 出版日期2012-1-6