miR-188-5p inhibits tumour growth and metastasis in prostate cancer by repressing LAPTM4B expression
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Hongtuan Zhang1,2,3, Shiyong Qi1, Tao Zhang1, Andi Wang1, Ranlu Liu1, Jia Guo2, Yuzhuo Wang2,3 and Yong Xu1
1 Department of Urology, National Key Specialty of Urology, Second Hospital of Tianjin Medical University, Tianjin Key Institute of Urology, Tianjin Medical University, Tianjin, China
2 Vancouver Prostate Centre & Department of Urologic Sciences, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada
3 Department of Experimental Therapeutics, British Columbia Cancer Agency, Vancouver, British Columbia, Canada
Yong Xu, email:
Keywords: miRNA, metastasis, miR-188-5p, prostate cancer, LAPTM4B
Received: December 14, 2014 Accepted: January 03, 2015 Published: January 21, 2015
Elucidation of the molecular targets and pathways regulated by the tumour-suppressive miRNAs can shed light on the oncogenic and metastatic processes in prostate cancer (PCa). Using miRNA profiling analysis, we find that miR-188-5p was significantly down-regulated in metastatic PCa. Down-regulation of miR-188-5p is an independent prognostic factor for poor overall and biochemical recurrence-free survival. Restoration of miR-188-5p in PCa cells (PC-3 and LNCaP) significantly suppresses proliferation, migration and invasion in vitro and inhibits tumour growth and metastasis in vivo. We also find overexpression of miR-188-5p in PC-3 cells can significantly enhance the cells’ chemosensitivity to adriamycin. LAPTM4B is subsequently identified as a direct target of miR-188-5p in PCa, and is found to be significantly over-expressed in PCa. Knockdown of LAPTM4B phenotypically copies miR-188-5p-induced phenotypes, whereas ectopic expression of LAPTM4B reverses the effects of miR-188-5p. We also find that restoration of miR-188-5p can inhibit the PI3K/AKT signaling pathway via the suppression of LAPTM4B. Taken together, this is the first report unveils that miR-188-5p acts as a tumour suppressor in PCa and may therefore serve as a useful therapeutic target for the development of new anticancer therapy.
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