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MicroRNA-766-3p Inhibits Tumour Progression by Targeting Wnt3a in Hepatocellular Carcinoma

  • You, Yu (Department of Hepatobiliary Surgery, the Second Affiliated Hospital of Chongqing Medical University) ;
  • Que, Keting (Department of Hepatobiliary Surgery, the Second Affiliated Hospital of Chongqing Medical University) ;
  • Zhou, Yun (Department of Hepatobiliary Surgery, the Second Affiliated Hospital of Chongqing Medical University) ;
  • Zhang, Zhen (Department of Hepatobiliary Surgery, the Second Affiliated Hospital of Chongqing Medical University) ;
  • Zhao, Xiaoping (Department of Hepatobiliary Surgery, the Second Affiliated Hospital of Chongqing Medical University) ;
  • Gong, Jianpin (Department of Hepatobiliary Surgery, the Second Affiliated Hospital of Chongqing Medical University) ;
  • Liu, Zuojin (Department of Hepatobiliary Surgery, the Second Affiliated Hospital of Chongqing Medical University)
  • Received : 2018.04.24
  • Accepted : 2018.07.12
  • Published : 2018.09.30

Abstract

Recent studies have indicated that microRNAs (miRNAs) play an important role in hepatocellular carcinoma (HCC) progression. In this study, we showed that miR-766-3p was decreased in approximately 72% of HCC tissues and cell lines, and its low expression level was significantly correlated with tumour size, TNM stage, metastasis, and poor prognosis in HCC. Ectopic miR-766-3p expression inhibited HCC cell proliferation, colony formation, migration and invasion. In addition, we showed that miR-766-3p repressed Wnt3a expression. A luciferase reporter assay revealed that Wnt3a was a direct target of miR-766-3p, and an inverse correlation between miR-766-3p and Wnt3a expression was observed. Moreover, Wnt3a up-regulation reversed the effects of miR766-3p on HCC progression. In addition, our study showed that miR-766-3p up-regulation decreased the nuclear ${\beta}-catenin$ level and expression of Wnt targets (TCF1 and Survivin) and reduced the level of MAP protein regulator of cytokinesis 1 (PRC1). However, these effects of miR-766-3p were reversed by Wnt3a up-regulation. In addition, PRC1 upregulation increased the nuclear ${\beta}-catenin$ level and protein expression of TCF1 and Survivin. iCRT3, which disrupts the ${\beta}-catenin-TCF4$ interaction, repressed the TCF1, Survivin and PRC1 protein levels. Taken together, our results suggest that miR-766-3p down-regulation promotes HCC cell progression, probably by targeting the Wnt3a/PRC1 pathway, and miR-766-3p may serve as a potential therapeutic target in HCC.

Keywords

References

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