Volume 15, Issue 6 (November 2013) 15, 735–741; 10.1038/aja.2013.80
miR-205 is frequently downregulated in prostate cancer and acts as a tumor suppressor by inhibiting tumor growth
Ning Wang*, Qi Li*, Ning-Han Feng, Gong Cheng, Zhao-Long Guan, Yang Wang, Chao Qin, Chang-Jun Yin and Li-Xin Hua
Department of Urology, First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China
*These authors contributed equally to this work.
Correspondence: Dr LX Hua, (wn6530289162@163.com)
Received 18 March 2013; Revised 11 April 2013; Accepted 18 May 2013 Advance online publication 26 August 2013
Abstract |
The purpose of this study was to elucidate the molecular mechanisms of microRNA-205 (miR-205) as a tumor suppressor in prostate cancer (PCa). In the present study, microRNA microarray analysis suggested that the expression of miR-205 was significantly decreased in advanced PCa compared with early PCa. Real-time PCR analysis also indicated that miR-205 expression was significantly decreased in PCa tissues compared with non-cancerous tissues. Moreover, the expression of miR-205 has been demonstrated to be associated with the clinicopathological stage and total/free prostate-specific antigen (PSA) level of PCa. Functional analyses showed that both the overexpression of miR-205 and the knockdown of c-SRC in PCa cell lines could inhibit cell growth, colony formation, migration, invasion and the cell cycle as well as induce cell apoptosis in vitro. Furthermore, over-expressing miR-205 reduced tumorigenicity in vivo. Through a luciferase activity assay and Western blotting, c-SRC was identified as a target of miR-205 in cells. The overexpression of miR-205 suppressed c-SRC and its downstream signaling molecules, including FAK, p-FAK, ERK1/2 and p-ERK1/2, and attenuated cell proliferation, invasion and tumor growth.
Keywords: c-SRC; miR-205; prostate cancer (PCa); tumor growth
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