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, p21Cip1 expression. 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.
Written by:
Wu Z, He B, He J, Mao X. Are you the author?
Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, P.R. China; Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, P.R. China.
Reference: Prostate. 2012 Oct 11. Epub ahead of print.
doi: 10.1002/pros.22600
PubMed Abstract
PMID: 23060044
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