MicroRNA let-7c Suppresses Androgen Receptor Expression and Activity via Regulation of Myc Expression in Prostate Cancer Cells.
- Resource Type
- Article
- Authors
- Nadiminty, Nagalakshmi; Tummala, Ramakumar; Lou, Wei; Zhu, Yezi; Zhang, Jin; Chen, Xinbin; DeVere White, Ralph W.; Kung, Hsing-Jien; Evans, Christopher P.; Gao, Allen C.
- Source
- Journal of Biological Chemistry. 1/6/2012, Vol. 287 Issue 2, following p1527-1537. 17p.
- Subject
- *PROSTATE cancer
*CASTRATION
*ANDROGENS
*CELL proliferation
*CANCER cells
- Language
- ISSN
- 0021-9258
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. [ABSTRACT FROM AUTHOR]