Downregulation of SUMO2 inhibits hepatocellular carcinoma cell proliferation, migration and invasion

FEBS Open Bio. 2021 Jun;11(6):1771-1784. doi: 10.1002/2211-5463.13173. Epub 2021 May 14.

Abstract

This study aimed to evaluate the prognostic value and biological function of small ubiquitin-like modifier 2 (SUMO2) in hepatocellular carcinoma (HCC). SUMO2 expression in HCC tissues was markedly higher than that in normal liver tissues, and patients with high SUMO2 expression had significantly shorter median overall survival than those with low SUMO2 expression. Furthermore, SUMO2 expression was closely correlated with lymph node metastasis and vascular invasion and was a predictor of poor prognosis. The knockdown of SUMO2 in two HCC cell lines (SMMC-7721 and Bel-7404) dramatically suppressed their proliferation, migration and invasion. Western blot analysis showed that the downregulation of SUMO2 significantly reduced the expression of Ki-67, matrix metalloproteinase-9 (MMP-9) and vascular endothelial growth factor (VEGF) in SMMC-7721 and Bel-7404 cells. Similarly, quantitative reverse transcription-PCR revealed consistently decreased expression of MMP-9 and VEGF. Our data suggest that SUMO2 promotes proliferation, migration and invasion of HCC cells via mechanisms involving MMP-9 and VEGF. Therefore, SUMO2 may be a prognostic factor and a promising therapeutic target for patients with HCC.

Keywords: liver cancer; matrix metalloproteinase-9; prognosis; small ubiquitin-like modifier; small ubiquitin-like modifier 2; vascular endothelial growth factor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Hepatocellular / metabolism*
  • Carcinoma, Hepatocellular / pathology
  • Cell Movement
  • Cell Proliferation
  • Down-Regulation*
  • Female
  • Humans
  • Liver Neoplasms / metabolism*
  • Liver Neoplasms / pathology
  • Male
  • Middle Aged
  • Small Ubiquitin-Related Modifier Proteins / genetics
  • Small Ubiquitin-Related Modifier Proteins / metabolism*
  • Tumor Cells, Cultured
  • Wound Healing

Substances

  • SUMO2 protein, human
  • Small Ubiquitin-Related Modifier Proteins