Shi Xu-Bao, Xue Lingru, Yang Joy, Ma Ai-Hong, Zhao Jianjun, Xu Ma, Tepper Clifford G, Evans Christopher P, Kung Hsing-Jien, deVere White Ralph W
Departments of Urology and Biochemistry and Molecular Medicine, University of California, Davis, School of Medicine, Sacramento, CA 95817, USA.
Proc Natl Acad Sci U S A. 2007 Dec 11;104(50):19983-8. doi: 10.1073/pnas.0706641104. Epub 2007 Dec 3.
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.
尽管前列腺癌(CaP)是美国男性中最常被诊断出的恶性肿瘤,也是癌症死亡的第二大主要原因,但解释CaP发生发展的机制仍大多未知。最近的研究表明,一些异常表达的微小RNA(miRNA)参与肿瘤发生。虽然在CaP中已发现某些miRNA的异常表达,但其在该疾病中的功能尚未明确。在本研究中,我们发现miR-125b在雄激素依赖和非依赖的CaP细胞以及良性和恶性前列腺组织中存在差异表达。此外,雄激素信号能够上调miR-125b的表达。另外,转染合成的miR-125b可刺激CaP细胞的雄激素非依赖性生长,并下调Bak1的表达。我们的结果表明,miR-125b作为一种癌基因,参与了CaP的发病机制。