SND1 overexpression deregulates cholesterol homeostasis in hepatocellular carcinoma

Biochim Biophys Acta. 2016 Sep;1861(9 Pt A):988-996. doi: 10.1016/j.bbalip.2016.05.011. Epub 2016 May 26.

Abstract

SND1 is a multifunctional protein participating, among others, in gene transcription and mRNA metabolism. SND1 is overexpressed in cancer cells and promotes viability and tumourigenicity of hepatocellular carcinoma cells. This study shows that cholesterol synthesis is increased in SND1-overexpressing hepatoma cells. Neither newly synthesised nor extracellularly supplied cholesterol are able to suppress this increase; however, inhibition of cholesterol esterification reverted the activated state of sterol-regulatory element-binding protein 2 (SREBP2) and cholesterogenesis. These results highlight SND1 as a potential regulator of cellular cholesterol distribution and homeostasis in hepatoma cells, and support the rationale for the therapeutic use of molecules that influence cholesterol management when SND1 is overexpressed.

Keywords: Cancer metabolism; Cholesterol; Hepatoma; SND1; SREBP2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / metabolism
  • Carcinoma, Hepatocellular / pathology
  • Cell Line, Tumor
  • Cholesterol / biosynthesis*
  • Cholesterol / genetics
  • Endonucleases
  • Gene Expression Regulation, Neoplastic
  • Homeostasis
  • Humans
  • Lipid Metabolism / genetics
  • Liver / metabolism
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / pathology
  • Nuclear Proteins / biosynthesis*
  • Nuclear Proteins / genetics
  • Sterol Regulatory Element Binding Protein 2 / genetics
  • Sterol Regulatory Element Binding Protein 2 / metabolism

Substances

  • Nuclear Proteins
  • SREBF2 protein, human
  • Sterol Regulatory Element Binding Protein 2
  • Cholesterol
  • Endonucleases
  • SND1 protein, human