Reactive oxygen species-dependent down-regulation of tumor suppressor genes PTEN, USP28, DRAM, TIGAR, and CYLD under oxidative stress

Biochem Genet. 2013 Dec;51(11-12):901-15. doi: 10.1007/s10528-013-9616-7. Epub 2013 Jul 6.

Abstract

We examined whether steady-state mRNA levels of five tumor suppressor genes are subjected to oxidative stress. Superoxide radical-generating menadione and serum deprivation diminished the steady-state mRNA levels for the genes phosphatase and tensin homolog (PTEN), ubiquitin specific peptidase 28 (USP28), damage-regulated autophagy modulator (DRAM), TP53-induced glycolysis and apoptosis regulator (TIGAR), and cylindromatosis (CYLD). Hydrogen peroxide showed suppression in steady-state mRNA levels for USP28, DRAM, TIGAR, and CYLD but not for PTEN. The steady-state mRNA levels specific for all five genes were enhanced by antioxidants, such as glutathione and N-acetylcysteine. The HepG2 stable transfectants overexpressing the mitochondrial isoform of human glutaredoxin, Grx2a, and containing a relatively low reactive oxygen species (ROS) level were assessed to contain the increased steady-state mRNA levels specific for the five tumor suppressor genes. In brief, the steady-state mRNA levels specific for these genes are negatively regulated by oxidative stress through the mediation of ROS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antioxidants / metabolism
  • Apoptosis Regulatory Proteins
  • Deubiquitinating Enzyme CYLD
  • Down-Regulation
  • Gene Expression
  • Genes, Tumor Suppressor*
  • Glutaredoxins / genetics
  • Hep G2 Cells
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics*
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Membrane Proteins / genetics*
  • Membrane Proteins / metabolism
  • Mitochondria / genetics
  • Mitochondria / metabolism
  • Oxidative Stress / genetics*
  • PTEN Phosphohydrolase / genetics*
  • PTEN Phosphohydrolase / metabolism
  • Phosphoric Monoester Hydrolases
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Reactive Oxygen Species / metabolism
  • Superoxides / metabolism
  • Tumor Cells, Cultured
  • Tumor Suppressor Proteins / genetics*
  • Tumor Suppressor Proteins / metabolism
  • Ubiquitin Thiolesterase / genetics*
  • Ubiquitin Thiolesterase / metabolism

Substances

  • Antioxidants
  • Apoptosis Regulatory Proteins
  • DRAM1 protein, human
  • Glutaredoxins
  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins
  • RNA, Messenger
  • Reactive Oxygen Species
  • Tumor Suppressor Proteins
  • USP28 protein, human
  • Superoxides
  • Phosphoric Monoester Hydrolases
  • TIGAR protein, human
  • PTEN Phosphohydrolase
  • PTEN protein, human
  • CYLD protein, human
  • Deubiquitinating Enzyme CYLD
  • Ubiquitin Thiolesterase