Upregulation of miR-200b Inhibits Hepatocellular Carcinoma Cell Proliferation and Migration by Targeting HMGB3 Protein

Technol Cancer Res Treat. 2018 Jan 1:17:1533033818806475. doi: 10.1177/1533033818806475.

Abstract

HMGB3 belongs to the high-mobility group box subfamily and has been found to be overexpressed in gastric cancer. However, the expression and the role of HMGB3 in human hepatocellular carcinoma remain unknown. Here, we report that HMGB3, which is suppressed by miR-200b, contributes to cell proliferation and migration in human hepatocellular carcinoma. After analyzing The Cancer Genome Atlas data of 371 patients with hepatocellular carcinoma, we identified HMGB3 to be upregulated in human hepatocellular carcinoma tissue. Knockdown of HMGB3 in the hepatocellular carcinoma cell line suppressed cell proliferation and migration. TargetScan analysis showed miR-200b to be a possible regulator for HMGB3. Subsequent luciferase assays indicated that HMGB3 was a direct target of miR-200b. In addition, upregulation of miR-200b inhibited hepatocellular carcinoma cell growth and migration. HMGB3 overexpression or miR-200b downregulation was associated with poor prognosis. Our findings suggest HMGB3 may serve as an important oncoprotein whose expression is negatively regulated by miR-200b in hepatocellular carcinoma.

Keywords: HMGB3; human hepatocellular carcinoma; miR-200b; prognosis; tumor progression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions
  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / mortality
  • Carcinoma, Hepatocellular / pathology
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Disease Progression
  • Gene Expression Regulation, Neoplastic*
  • HMGB3 Protein / genetics*
  • Humans
  • Kaplan-Meier Estimate
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / mortality
  • Liver Neoplasms / pathology
  • MicroRNAs / genetics*
  • Prognosis
  • RNA Interference*

Substances

  • 3' Untranslated Regions
  • HMGB3 Protein
  • MIRN200 microRNA, human
  • MicroRNAs