MiR-329-3p inhibits hepatocellular carcinoma cell proliferation and migration through USP22-Wnt/β-Catenin pathway

Eur Rev Med Pharmacol Sci. 2020 Oct;24(19):9932-9939. doi: 10.26355/eurrev_202010_23204.

Abstract

Objective: MicroRNA-329-3p (miR-329-3p) has been shown to be involved in tumor development. But its role in hepatocellular carcinoma has not been explored. Our study aims to explore the effect and mechanism of miR-329-3p on hepatocellular carcinoma development.

Patients and methods: Hepatocellular carcinoma tissues and paired paracancerous specimens from 31 hepatocellular carcinoma patients undergoing surgery were collected. Quantitative real-time polymerase chain reaction and Western blot were employed to measure genes expression at mRNA and protein level. CCK-8 and transwell assays were performed to evaluate hepatocellular carcinoma cells proliferation and migration. Dual-Luciferase reporter gene assay was designed to validate the target gene of miR-329-3p.

Results: Our study showed miR-329-3p expression was significantly lower in hepatocellular carcinoma tissue. MiR-329-3p mimic inhibits proliferation and migration of HepG2 cells. By using Dual-Luciferase reporter gene assay, we proved that miR-329-3p inhibited HepG2 cell proliferation and migration by targeting USP22 directly. By up- and downregulation of USP22 expression, we also proved that USP22 can activate the Wnt/β-Catenin pathway, which in turn affected the proliferation and migration of HepG2 cells.

Conclusions: We demonstrated that miR-329-3p can inhibit HepG2 cell proliferation and migration by inhibiting USP22-Wnt/β-Catenin pathway. Our study provides novel insights into the aetiology and potential treatment of hepatocellular carcinoma.

MeSH terms

  • Carcinoma, Hepatocellular / metabolism*
  • Carcinoma, Hepatocellular / pathology
  • Cell Movement
  • Cell Proliferation
  • Humans
  • Liver Neoplasms / metabolism*
  • Liver Neoplasms / pathology
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Tumor Cells, Cultured
  • Ubiquitin Thiolesterase / genetics
  • Ubiquitin Thiolesterase / metabolism*
  • Wnt Signaling Pathway
  • beta Catenin / metabolism*

Substances

  • MIRN329 microRNA, human
  • MicroRNAs
  • beta Catenin
  • Ubiquitin Thiolesterase
  • Usp22 protein, human