Department of Urology, University of California at Davis, Sacramento, California 95817, USA.
J Biol Chem. 2012 Jan 6;287(2):1527-37. doi: 10.1074/jbc.M111.278705. Epub 2011 Nov 28.
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.
去势抵抗性前列腺癌仍然依赖于雄激素受体 (AR) 的表达。AR 在前列腺癌的发生和去势治疗后的进展中发挥着核心作用。在这里，我们确定了 miR-let-7c 是 AR 表达的关键调节因子。miR-let-7c 通过靶向其转录物 c-Myc 来抑制人前列腺癌细胞中 AR 的表达和活性。Let-7c 对 AR 的抑制作用导致人前列腺癌细胞增殖减少。前列腺癌标本中 Let-7c 的下调与 AR 表达呈负相关，而 Lin28（let-7 的抑制物）的表达与 AR 表达呈正相关。我们的研究表明，miRNA let-7c 通过下调 AR 表达在前列腺癌中调节雄激素信号转导方面发挥着重要作用。这些结果表明，miR-let-7c 的再构成可能有助于靶向晚期前列腺癌中增强和超敏的 AR。
