Downregulation of miR-221, -30d, and -15a Contributes to Pathogenesis of Prostate Cancer by Targeting Bmi-1

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Hanqing Xuan, Wei Xue^*, Jiahua Pan, Jianjun Sha, Baijun Dong, and Yiran Huang

Department of Urology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, No. 1630 Dong Fang Road, Shanghai 2000127, China; fax: +86-21-6838-3716; E-mail: weixuerh@sohu.com; xuanhq@163.com

^* To whom correspondence should be addressed.

Received May 20, 2014; Revision received August 3, 2014

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Prostate cancer is the second leading cause of cancer-related deaths of men. Bmi-1, a member of PcG family of proteins, has been implicated in the pathogenesis of prostate cancer, and disturbed profile of microRNAs (miRNAs) has been found in prostate cancer tissues. How Bmi-1 is regulated by miRNAs is unclear. In this study, we screened 18 miRNAs that potentially repress the expression of Bmi-1 using a dual luciferase system and found that 12 miRNAs could bind with the 3′-untranslated region of Bmi-1 mRNA. Using qRT-PCR, we found that expression of miR-221, -15a, and -30d was significantly reduced in prostate cancer tissues. Subsequent functional study indicated that miR-221 and miR-30d can repress prostate cancer cell proliferation, and this effect can be partially rescued by Bmi-1 overexpression. Our study constructs the relation between downregulated miR-221 and miR-30d and prostate cancer pathogenesis. These results indicate that miR-221 and miR-30d are candidate tumor suppressor miRNAs in prostate cancer and therefore serve as potential clinical classification markers and therapeutic targets for human prostate cancer.

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KEY WORDS: miRNA, prostate cancer, Bmi-1, cell proliferation

DOI: 10.1134/S0006297915030037

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