Tumor Biology

, Volume 37, Issue 12, pp 15627–15633 | Cite as

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

  • Feng Liu
  • Jihong Wang
  • Qiang Fu
  • Xinru Zhang
  • Ying Wang
  • Jialin Liu
  • Jianwen Huang
  • Xiangguo Lv
Original Article

Abstract

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.

Keywords

Prostate cancer Cisplatin Autophagy Beclin-1 miR-144 VEGF 

Notes

Conflicts of interest

None

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Feng Liu
    • 1
  • Jihong Wang
    • 2
  • Qiang Fu
    • 2
  • Xinru Zhang
    • 2
  • Ying Wang
    • 3
  • Jialin Liu
    • 4
  • Jianwen Huang
    • 2
  • Xiangguo Lv
    • 2
  1. 1.Department of UrologyShanghai Fengxian District Central HospitalShanghaiChina
  2. 2.Department of UrologyShanghai Jiaotong University Affiliated the Sixth People’s HospitalShanghaiChina
  3. 3.Department of UrologyShanghai the Fifth People’s HospitalShanghaiChina
  4. 4.School of Biomedical EngineeringShanghai Jiao Tong UniversityShanghaiChina

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