Reactive Oxygen Species-Dependent Down-Regulation of Tumor Suppressor Genes PTEN, USP28, DRAM, TIGAR, and CYLD Under Oxidative Stress
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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.
KeywordsTumor suppressor Reactive oxygen species Glutathione Serum deprivation Glutaredoxin
This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT & Future Planning (2013-022019). This study is supported in part by Kangwon National University.
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