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

Mol Cells. 2018 Sep 30;41(9):830-841. doi: 10.14348/molcells.2018.0181. Epub 2018 Aug 27.

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 miR-766-3p on HCC progression. In addition, our study showed that miR-766-3p up-regulation decreased the nuclear β-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 up-regulation increased the nuclear β-catenin level and protein expression of TCF1 and Survivin. iCRT3, which disrupts the β-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: Wnt3a; hepatocellular carcinoma; invasion; miR-766-3p; proliferation.

MeSH terms

  • Aged
  • Animals
  • Carcinoma, Hepatocellular / metabolism
  • Carcinoma, Hepatocellular / pathology*
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Disease Progression*
  • Female
  • Humans
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / pathology*
  • Male
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Middle Aged
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • Neoplasm Staging
  • Survivin / metabolism
  • Wnt3A Protein / genetics
  • Wnt3A Protein / metabolism*
  • Xenograft Model Antitumor Assays
  • beta Catenin / metabolism

Substances

  • BIRC5 protein, human
  • CTNNB1 protein, human
  • MIRN766 microRNA, human
  • MicroRNAs
  • Survivin
  • WNT3A protein, human
  • Wnt3A Protein
  • beta Catenin