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Reactive Oxygen Species-Dependent Down-Regulation of Tumor Suppressor Genes PTEN, USP28, DRAM, TIGAR, and CYLD Under Oxidative Stress

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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.

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Acknowledgments

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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Authors and Affiliations

  1. Department of Biochemistry, Kangwon National University, Hyoja-2-dong, 192-1, Chuncheon, 200-701, Korea

    Su-Jung Kim & Chang-Jin Lim

  2. Department of Anatomy, Yonsei University College of Medicine, Seoul, 120-749, Korea

    Hyun-Joo Jung

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  1. Su-Jung Kim
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Correspondence to Chang-Jin Lim.

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S.-J. Kim and H.-J. Jung contributed equally to this work.

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Kim, SJ., Jung, HJ. & Lim, CJ. Reactive Oxygen Species-Dependent Down-Regulation of Tumor Suppressor Genes PTEN, USP28, DRAM, TIGAR, and CYLD Under Oxidative Stress. Biochem Genet 51, 901–915 (2013). https://doi.org/10.1007/s10528-013-9616-7

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