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

Authors

  • Ziqing Wu,

    1. Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, P.R. China
    2. Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, P.R. China
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  • Benfu He,

    1. Department of Oncology, 421th Hospital of PLA., Guangzhou, P.R. China
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  • Jincan He,

    1. Department of Urology, Nanfang Hospital, Southern Medical University, Guangzhou, P.R. China
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  • Xiangming Mao

    Corresponding author
    1. Department of Urology, Nanfang Hospital, Southern Medical University, Guangzhou, P.R. China
    • Department of Urology, Nanfang Hospital Affiliated to Southern Medical University, #1838 North Guangzhou Road, Guangzhou, Guangdong 510515, P.R. China.
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  • Ziqing Wu and Benfu He contributed equally to this work.

Abstract

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.

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