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

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• 作者：Feng Liu ; Jihong Wang ; Qiang Fu ; Xinru Zhang ; Ying Wang ; Jialin Liu…
• 关键词：Prostate cancer ; Cisplatin ; Autophagy ; Beclin ; 1 ; miR ; 144 ; VEGF
• 刊名：Tumor Biology
• 出版年：2016
• 出版时间：December 2016
• 年：2016
• 卷：37
• 期：12
• 页码：15627-15633
• 全文大小：
• 刊物主题：Cancer Research;
• 出版者：Springer Netherlands
• ISSN：1423-0380
• 卷排序：37

文摘

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.