expression and no change in expression was observed in cells treated with cysteine alone. These results suggest that oxidative stress may play a role in the alteration of miRNA expression due to radiation. In this study, we show that alterations in miRNA expression due to ionizing radiation are also produced in response to other agents that induce either DNA damage or oxidative stress. Furthermore, there appears to be substantial overlap between the specific changes in miRNA expression. The miRNA species that are changed by radiation are also altered after treatment with H2O2, which imposes a free radical stress, or with etoposide, which generates double strand breaks mimicking the direct DNA damage caused by radiation. Therefore, it seems reasonable to suggest a potentially common miRNA signatures in response to these genotoxic agents. Two miRNA species were altered by both radiation and H2O2 and eight species were altered by both radiation and etoposide. In each instance, the YYA-021 direction of the change in expression following radiation exposure correlated with the direction of the change in expression resulting from either H2O2 or etoposide. The expression of seven miRNA species was changed by all three genotoxic agents and, once again, the direction of the change resulting from ionizing radiation corresponded with the direction of the change caused by either etoposide or H2O2. Furthermore, the magnitude of the change in expression of selected miRNA species correlated with both the radiation dose and with time after radiation exposure. We also show that the response to radiation can be 923564-51-6 abrogated by the addition of the free radical scavenger cysteine. Taken together, these data suggest that miRNA expression is responsive to cell stress resulting from both DNA damage and free radical formation provoking what appears to be a common expression signature of exogenous genotoxic stress. Since miRNAs control gene expression at the post-transcriptional level, they enable the cell to alter expression of a gene product very rapidly compared to mechanisms that alter transcriptional activity or protein degradation. The association with radiation dose also suggests that this rapid response can be modulated to respond to the severity of the insult. This mechanism may allow a cell to respond with a preprogrammed response to extracellular signals and stressors. It has previously been shown that several miRNA species are associated with DNA repair processes. For example
