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BIOLOGICAL SCIENCES / MEDICAL SCIENCES
An androgen-regulated miRNA suppresses Bak1 expression and induces androgen-independent growth of prostate cancer cells

Xu-Bao Shi^*, Lingru Xue^*, Joy Yang^*, Ai-Hong Ma, Jianjun Zhao, Ma Xu, Clifford G. Tepper, Christopher P. Evans^*, Hsing-Jien Kung, and Ralph W. deVere White^*,

Departments of *Urology and Biochemistry and Molecular Medicine, University of California, Davis, School of Medicine, Sacramento, CA 95817; and National Research Institute for Family Planning, Peking Union Medical College, Beijing 100081, China

Edited by Carlo M. Croce, Ohio State University, Columbus, OH, and approved October 22, 2007 (received for review July 14, 2007)

Although prostate cancer (CaP) is the most frequently diagnosed malignant tumor and the second leading cause of cancer deaths in American men, the mechanisms explaining the development and progression of CaP remain largely unknown. Recent studies have shown that some aberrantly expressed microRNAs (miRNAs) are involved in tumorigenesis. Although aberrant expression of certain miRNAs has been discovered in CaP, their function in this disease has not yet been defined. In this study, we found differential expression of miR-125b in androgen-dependent and independent CaP cells, as well as in benign and malignant prostate tissues. Furthermore, androgen signaling was able to up-regulate the expression of miR-125b. In addition, transfection of synthetic miR-125b stimulated androgen-independent growth of CaP cells and down-regulated the expression of Bak1. Our results suggest that miR-125b acts as an oncogene, contributing to the pathogenesis of CaP.

microRNA | miR-125b | ISH | LNCaP

The authors declare no conflict of interest.

This article is a PNAS Direct Submission.

This article contains supporting information online at www.pnas.org/cgi/content/full/0706641104/DC1.

To whom correspondence should be addressed at: Department of Urology, University of California, Davis, School of Medicine, 4860 Y Street, Suite 3500, Sacramento, CA 95817. E-mail: rwdeverewhite{at}ucdavis.edu

© 2007 by The National Academy of Sciences of the USA

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