An androgen-regulated miRNA suppresses Bak1 expression and induces androgen-independent growth of prostate cancer cells.
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.
Departments of Urology and Biochemistry and Molecular Medicine, University of California, Davis, School of Medicine, Sacramento, CA 95817, USA.
Xu-Bao
XB
Shi
Lingru
L
Xue
Joy
J
Yang
Ai-Hong
AH
Ma
Jianjun
J
Zhao
Ma
M
Xu
Clifford G
CG
Tepper
Christopher P
CP
Evans
Hsing-Jien
HJ
Kung
Ralph W
RW
deVere White
D000728:Androgens / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects*; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D015854:Up-Regulation / Q000187:drug effects; D050998:bcl-2 Homologous Antagonist-Killer Protein / Q000235:genetics / Q000378:metabolism*
D000728:Androgens; C494772:BAK1 protein, human; D035683:MicroRNAs; D050998:bcl-2 Homologous Antagonist-Killer Protein