The roles of HIF-DEC pathway on DNA repair systems in hypoxic oral cancer cells.

在本研究中，我们分析了许多DNA修复相关基因在低氧条件下的表达变化，进一步注意到这些变化对辐射敏感性的影响。综合基因表达分析表明，在130个DNA修复相关基因中，有50个基因在低氧条件下表达下调。在这些基因中，我们选择了6个基因，并证实了数量减少的表达。共转染报告实验表明，DEC1或DEC2抑制了这些DNA修复相关基因的启动子活性。此外，HIF1a或DEC2的敲除减弱了低氧对DNA修复相关基因表达的抑制。有趣的是，DNA双链断裂的检测和修复在低氧预孵育的细胞中受到抑制。此外，DEC2基因的敲除增加了这些细胞对辐射的敏感性。提示HIF-1-DEC途径，尤其是DEC2途径，通过抑制DNA修复基因的表达，在辐射敏感性中起关键作用。

In this study, we analyzed expression changes of numerous DNA repair-related genes under hypoxia, further noted that the effect of the changes to radiation sensitivities. Comprehensive gene expression analyses showed that 50 of 130 DNA repair-related genes were included in down-regulated genes under hypoxia. Among these genes we selected 6 genes and confirmed quantitative decreased expressions. Co-transfection reporter assay elucidated that DEC1 or DEC2 repressed those DNA repair-related genes promoter activities. In addition, knockdown of HIF1A or DEC2 attenuated hypoxic suppression of DNA repair-related gene expressions. Interestingly, detection and repair of DNA double-strand breaks by irradiations were inhibited in hypoxic pre-incubated cells. Moreover, knockdown of DEC2 increased radiation sensitivities in those cells. These data suggested that HIF-1-DEC pathway especially DEC2 play a pivotal role in radiation sensitivity via suppression of DNA repair gene expressions.