MicroRNA Let-7a Inhibits Proliferation of Human Prostate Cancer Cells In Vitro and In Vivo by Targeting E2F2 and CCND2 |
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| Authors: | Qingchuan Dong Ping Meng Tao Wang Weiwei Qin Weijun Qin Fuli Wang Jianlin Yuan Zhinan Chen Angang Yang He Wang |
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| Institution: | 1. Department of Urology, Xijing Hospital, Fourth Military Medical University, Xi''an, China.; 2. Department of Biochemistry, Fourth Military Medical University, Xi''an, China.; 3. Cell Engineering Research Center, State Key Laboratory of Cancer Biology, Fourth Military Medical University, Xi''an, China.;Health Canada, Canada |
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| Abstract: | BackgroundPrevious work has shown reduced expression levels of let-7 in lung tumors. But little is known about the expression or mechanisms of let-7a in prostate cancer. In this study, we used in vitro and in vivo approaches to investigate whether E2F2 and CCND2 are direct targets of let-7a, and if let-7a acts as a tumor suppressor in prostate cancer by down-regulating E2F2 and CCND2.Methodology/PrincipalFindings Real-time RT-PCR demonstrated that decreased levels of let-7a are present in resected prostate cancer samples and prostate cancer cell lines. Cellular proliferation was inhibited in PC3 cells and LNCaP cells after transfection with let-7a. Cell cycle analysis showed that let-7a induced cell cycle arrest at the G1/S phase. A dual-luciferase reporter assay demonstrated that the 3′UTR of E2F2 and CCND2 were directly bound to let-7a and western blotting analysis further indicated that let-7a down-regulated the expression of E2F2 and CCND2. Our xenograft models of prostate cancer confirmed the capability of let-7a to inhibit prostate tumor development in vivo.Conclusions/SignificanceThese findings help to unravel the anti-proliferative mechanisms of let-7a in prostate cancer. Let-7a may also be novel therapeutic candidate for prostate cancer given its ability to induce cell-cycle arrest and inhibit cell growth, especially in hormone-refractory prostate cancer. |
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