Upregulation of RUNX1 Suppresses Proliferation and Migration through Repressing VEGFA Expression in Hepatocellular Carcinoma

Pathol Oncol Res. 2020 Apr;26(2):1301-1311. doi: 10.1007/s12253-019-00694-1. Epub 2019 Jul 9.

Abstract

Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer, and occurs in people with chronic liver diseases. Current treatment methods include surgery, transplant, and chemotherapy. Our study demonstrates runt-related transcription factor 1 (RUNX1) as a novel molecule in the initiation and development of HCC, and the role of its interaction with vascular endothelial growth factor A (VEGFA) in HCC. We showed the suppressive role of RUNX1 in the proliferation and migration of hepatocytes. In addition, the repressor RUNX1 functioned as a transcription factor on the promoter of VEGFA to inhibit the expression of VEGFA. Study in the HCC cells demonstrated that the suppression of HCC proliferation and migration was masked in the presence of overexpressed VEGFA. Introduction of RUNX1 into HCC mice model significantly limited the tumor growth. In summary, our study demonstrated that RUNX1 functions as a repressor in the HCC and this suppressive function was dependent on its effect on VEGFA.

Keywords: Hepatocelluar carcinoma; RUNX1; Tumor suppression; VEGFA.

MeSH terms

  • Animals
  • Carcinoma, Hepatocellular / pathology*
  • Cell Movement / physiology
  • Cell Proliferation / physiology
  • Core Binding Factor Alpha 2 Subunit / metabolism*
  • Gene Expression Regulation, Neoplastic / physiology
  • Humans
  • Liver Neoplasms / pathology*
  • Mice
  • Up-Regulation
  • Vascular Endothelial Growth Factor A / metabolism*

Substances

  • Core Binding Factor Alpha 2 Subunit
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • vascular endothelial growth factor A, mouse