Dgat2 reduces hepatocellular carcinoma malignancy via downregulation of cell cycle-related gene expression

Biomed Pharmacother. 2019 Jul:115:108950. doi: 10.1016/j.biopha.2019.108950. Epub 2019 May 8.

Abstract

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths worldwide, mainly due to the absence of effective diagnostic biomarkers and therapeutic targets. Therefore, novel molecular targets are urgently needed, in order to formulate novel therapeutic approaches for this devastating disease. In the present study, we demonstrated that diacylglycerol acyltransferase 2 (Dgat2) was downregulated in human HCC tissues compared with in matched normal tissues. Furthermore, its high expression was significantly associated with longer survival. In addition, Dgat2 overexpression significantly suppressed HCC cell proliferation. in vivo studies, we revealed that the weight and volume of the tumors derived from Balb/c nude mice was markedly decreased when using HCC cells overexpressing Dgat2. Mechanism analysis demonstrated that cell cycle-related gene expressions were significantly downregulated in HCC cells overexpressing Dgat2. Taken together, these data suggest that Dgat2 is an important regulator of HCC cell proliferation, and could represent a potential anticancer target and diagnostic biomarker for HCC.

Keywords: Cell cycle; Dgat2; Hepatocellular carcinoma; Proliferation.

MeSH terms

  • Animals
  • Apoptosis / genetics
  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / mortality
  • Carcinoma, Hepatocellular / pathology
  • Cell Line, Tumor
  • Cell Proliferation / genetics*
  • Diacylglycerol O-Acyltransferase / genetics*
  • Down-Regulation
  • Gene Expression Regulation, Neoplastic*
  • Genes, cdc*
  • Humans
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / mortality
  • Liver Neoplasms / pathology
  • Male
  • Mice, Inbred BALB C
  • Mice, Nude
  • Survival Analysis
  • Up-Regulation

Substances

  • DGAT2 protein, human
  • Diacylglycerol O-Acyltransferase