Upregulation of miR-153 promotes cell proliferation via downregulation of the PTEN tumor suppressor gene in human prostate cancer

BACKGROUND Accumulating evidence indicates that microRNAs play a pivotal role in the development and progression of prostate cancer. The present study was aimed at clarifying the biological functions of miR‐153, one of the upregulated microRNAs in prostate cancers, and the signaling transduction induced by miR‐153. METHODS miR‐153 was identified to be overexpressed in prostate cancers. The probable biological function of miR‐153 in cellular proliferation was then examined by diverse assays, such as MTT, colony formation and BrdUrd incorporation assay. Moreover, real‐time PCR and western blotting analysis were applied to investigate the underlying molecular mechanism induced by miR‐153. Luciferase assays were used to determined the FOXO1 transactivity and the direct regulation of PTEN‐3′‐UTR by miR‐153. RESULTS High‐throughput method identified miR‐153 to be upregulated in prostate cancers, which is further confirmed by the upregulated expression in four paired prostate tumor/adjacent non‐cancerous tissues from the same patients. Further studies revealed that overexpression of miR‐153 promoted cell cycle transition and cell proliferation, while inhibition of miR‐153 reduced this effect. Moreover, miR‐153 overexpression in prostate cancer cells increased the G1/S transitional promoter, cyclin D1 expression, and decreased cyclin‐dependent kinase (CDK) inhibitor, p21Cip1expression. In addition, we demonstrated that miR‐153 directly targeted the PTEN tumor suppressor gene, activated the AKT signaling and downregulated FOXO1 transcriptional activity. CONCLUSIONS Taken together, our results suggest that miR‐153 play an important role in promoting proliferation of human prostate cancer cells and present a novel mechanism of microRNA‐mediated direct suppression of PTEN expression in prostate cancer cells. Prostate 73: 596–604, 2013. © 2012 Wiley Periodicals, Inc.