HERC4 Is Overexpressed in Hepatocellular Carcinoma and Contributes to the Proliferation and Migration of Hepatocellular Carcinoma Cells

DNA Cell Biol. 2017 Jun;36(6):490-500. doi: 10.1089/dna.2016.3626. Epub 2017 Apr 21.

Abstract

Recently, more and more evidences unveiled that ubiquitin-proteasome system (UPS) makes an important contribution to the occurrence and development of cancer. HERC4 is one identified Ubiqutin ligase E3, a member of UPS. Although some studies showed that HERC4 abnormally expresses in many cancer cells, till now, nothing has been reported about the function of HERC4 in the development of hepatoma carcinoma. To this end, in this study, we studied the function of HERC4 for the first time in hepatoma carcinoma cells. We detected the expression of HERC4 in tumor and normal tissues, and in hepatoma carcinoma cell lines by using qRT-PCR, Western blot, immunohistochemistry, and immunofluorescence. The data showed that tumor tissues expressed higher HERC4 than normal ones. HERC4 was expressed, although to a different extent, in hepatoma carcinoma cell lines. Colony formation assay, CCK-8 assay, EdU assay, wound healing assay, and FACS indicated that HERC4 plays a role in cell proliferative and migration ability. HERC4 overexpression increases the proliferative and migration ability and reduces apoptosis of hepatoma carcinoma cells; in contrast, knockdown of HERC4 decreases the proliferative and migration ability and increases the apoptosis rate of hepatoma carcinoma cells. Taken together, our findings showed that HERC4 has an effect on the occurrence and development of hepatoma carcinoma by promoting hepatoma carcinoma cell proliferation and migration, and by reducing cell apoptosis, further providing another therapeutic target for the intervention of related diseases.

Keywords: HERC4; apoptosis; hepatoma carcinoma; migration; proliferation.

MeSH terms

  • Apoptosis
  • Carcinoma, Hepatocellular / pathology*
  • Cell Line, Tumor
  • Cell Movement*
  • Cell Proliferation
  • Cell Survival
  • Gene Expression Regulation, Neoplastic*
  • Gene Knockdown Techniques
  • Humans
  • Liver Neoplasms / pathology*
  • Ubiquitin-Protein Ligases / deficiency
  • Ubiquitin-Protein Ligases / genetics*
  • Ubiquitin-Protein Ligases / metabolism*

Substances

  • HERC4 protein, human
  • Ubiquitin-Protein Ligases