microRNA-183 is an oncogene targeting Dkk-3 and SMAD4 in prostate cancer

Department of Urology, San Francisco Veterans Affairs Medical Center, University of California at San Francisco, 4150 Clement Street, San Francisco, CA 94121, USA.
British Journal of Cancer (Impact Factor: 4.82). 03/2013; 108(8). DOI: 10.1038/bjc.2013.125
Source: PubMed

ABSTRACT Background:The purpose of this study was to identify prostate cancer (PC) oncogenic microRNAs (miRs) based on miR microarray and to investigate whether these oncogenic miRs may be useful as PC biomarkers.Methods:Initially, we carried out miR microarray and real-time PCR using RWPE-1, PC-3, DU-145 and LNCaP cells. To investigate the function of miR-183, we used a miR-183 knockdown inhibitor in cell growth and wound-healing assays. We used several algorithms and confirmed that they are directly regulated by miR-183.Results:We identified three potential oncogenic miRs (miR-146a, miR-183 and miR-767-5P). The expression of miR-183 in PC cells (PC-3, DU-145 and LNCaP) was upregulated compared with RWPE-1 cells. MiR-183 expression was also significantly higher in PC tissues compared with that in matched normal prostate tissues. Additionally, miR-183 expression was correlated with higher prostate-specific antigen, higher pT and shorter overall survival. MiR-183 knockdown decreased cell growth and motility in PC cells and significantly decreased prostate tumour growth in in vivo nude mice experiments. We identified Dkk-3 and SMAD4 as potential target genes of miR-183.Conclusion:Our data suggest that oncogenic miR-183 may be useful as a new PC biomarker and that inhibition of miR-183 expression may be therapeutically beneficial as a PC treatment.British Journal of Cancer advance online publication, 28 March 2013; doi:10.1038/bjc.2013.125

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