Reactive Oxygen Species-Dependent Down-Regulation of Tumor Suppressor Genes PTEN, USP28, DRAM, TIGAR, and CYLD Under Oxidative Stress
Reactive Oxygen Species-Dependent Down-Regulation of Tumor Suppressor Genes PTEN, USP28, DRAM, TIGAR, and CYLD Under Oxidative Stress
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DOI：
10.1007/s10528-013-9616-7
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发表时间：
2013-12-01
影响因子：
2.4
通讯作者：
Lim, Chang-Jin
中科院分区：
文献类型：
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作者：
Kim, Su-Jung;Jung, Hyun-Joo;Lim, Chang-Jin
我们检查了五个肿瘤抑制基因的稳定状态的mRNA水平是否受到氧化应激的影响。超氧阴离子自由基生成甲萘二酮和血清剥夺降低了磷酸酶和紧张素同源物(PTEN)、泛素特异肽酶28(USP28)、损伤调节自噬调节器(DRAM)、TP53诱导的糖酵解和凋亡调节因子(TIGAR)和圆柱瘤病(CyLD)等基因的稳态mRNA水平。过氧化氢对USP28、DRAM、TIGAR和CyLD的稳态mRNA水平有抑制作用，但对PTEN没有抑制作用。谷胱甘肽和N-乙酰半胱氨酸等抗氧化剂提高了所有五个基因的稳定状态mRNA水平。对高表达人谷氧还蛋白线粒体亚型Grx2a并且含有相对较低的活性氧物种(ROS)水平的HepG2稳定转染体进行了评估，以包含针对这五个肿瘤抑制基因的高水平的稳态mRNA。简而言之，氧化应激通过ROS的调节作用对这些基因的稳定的mRNA水平进行负调控。
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.