VEGF-activated miR-144 regulates autophagic survival of prostate cancer cells against Cisplatin

Cisplatin is a commonly used chemotherapy drug for prostate cancer (PC). However, some PCs are resistant to cisplatin treatment, while the molecular mechanisms underlying the resistance of PCs to cisplatin are not completely understood.

In this study, we found that cisplatin dose-dependently activated Beclin-1 in two PC cell lines, PC3 and LNCap. Autophagy suppression significantly increased the cisplatin-induced cell death of these PC cells in a CCK-8 assay. Moreover, microRNA (miR)-144 levels were significantly downregulated in cisplatin-treated PC cells, in a VEGF-dependent manner. Bioinformatics analysis showed that miR-144 targeted the 3'-UTR of Beclin-1 mRNA to inhibit its translation, which was confirmed by luciferase reporter assay. In PC patients after cisplatin treatment, low miR-144 levels appeared to predict poor outcome of patients' survival. Together, these data suggest that cisplatin may induce VEGF to suppress miR-144 levels in PC cells, which subsequently upregulates Beclin-1 to increase autophagic cell survival against cisplatin-induced cell death. Upregulation of miR-144 or suppression of cell autophagy may improve the outcome of cisplatin therapy in PC.

Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine. 2015 Nov 13 [Epub ahead of print]

Feng Liu, Jihong Wang, Qiang Fu, Xinru Zhang, Ying Wang, Jialin Liu, Jianwen Huang, Xiangguo Lv

Department of Urology, Shanghai Fengxian District Central Hospital, Shanghai, 201499, China. , Department of Urology, Shanghai Jiaotong University Affiliated the Sixth People's Hospital, 600 Yishan Road, Shanghai, 200233, China. Department of Urology, Shanghai Jiaotong University Affiliated the Sixth People's Hospital, 600 Yishan Road, Shanghai, 200233, China. , Department of Urology, Shanghai Jiaotong University Affiliated the Sixth People's Hospital, 600 Yishan Road, Shanghai, 200233, China. , Department of Urology, Shanghai the Fifth People's Hospital, Shanghai, China. , School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China. , Department of Urology, Shanghai Jiaotong University Affiliated the Sixth People's Hospital, 600 Yishan Road, Shanghai, 200233, China. , Department of Urology, Shanghai Jiaotong University Affiliated the Sixth People's Hospital, 600 Yishan Road, Shanghai, 200233, China.

PubMed