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

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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.