PSMD1 and PSMD2 regulate HepG2 cell proliferation and apoptosis via modulating cellular lipid droplet metabolism

BMC Mol Biol. 2019 Nov 8;20(1):24. doi: 10.1186/s12867-019-0141-z.

Abstract

Background: Obesity and nonalcoholic steatohepatitis (NASH) are well-known risk factors of hepatocellular carcinoma (HCC). The lipid-rich environment enhances the proliferation and metastasis abilities of tumor cells. Previous studies showed the effect of the ubiquitin-proteasome system (UPS) on tumor cell proliferation. However, the underlying mechanism of UPS in regulating the proliferation of lipid-rich tumor cells is not totally clear.

Results: Here, we identify two proteasome 26S subunits, non-ATPase 1 and 2 (PSMD1 and PSMD2), which regulate HepG2 cells proliferation via modulating cellular lipid metabolism. Briefly, the knockdown of PSMD1 and/or PSMD2 decreases the formation of cellular lipid droplets, the provider of the energy and membrane components for tumor cell proliferation. Mechanically, PSMD1 and PSMD2 regulate the expression of genes related to de novo lipid synthesis via p38-JNK and AKT signaling. Moreover, the high expression of PSMD1 and PSMD2 is significantly correlated with poor prognosis of HCC.

Conclusion: We demonstrate that PSMD1 and PSMD2 promote the proliferation of HepG2 cells via facilitating cellular lipid droplet accumulation. This study provides a potential therapeutic strategy for the treatment of lipid-rich tumors.

Keywords: Cell proliferation; Lipid droplet; PSMD1; PSMD2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis
  • Cell Proliferation
  • Hep G2 Cells
  • Humans
  • Lipid Droplets / metabolism*
  • Lipid Metabolism
  • MAP Kinase Signaling System
  • Proteasome Endopeptidase Complex / physiology*
  • Proto-Oncogene Proteins c-akt / metabolism
  • TNF Receptor-Associated Factor 2 / physiology*

Substances

  • PSMD1 protein, human
  • PSMD2 protein, human
  • TNF Receptor-Associated Factor 2
  • Proto-Oncogene Proteins c-akt
  • Proteasome Endopeptidase Complex