ATR是细胞中参与辐射应激响应的重要激酶，但目前对调控ATR的microRNA仍一无所知。我们的前期工作提示，miR-185对ATR具有靶向调控作用并能增加肿瘤细胞的辐射敏感性。本项目拟在此基础上采用点突变技术、诱导表达miR-185的细胞系、抑制剂等方法明确miR-185对ATR及其下游基因表达的靶向调控作用，并探讨ATR在microRNA发生中的作用，完善以ATR为核心的辐射生物效应的调控通路。最后通过细胞实验和动物实验探讨利用miR-185对ATR的负调控进行肿瘤细胞辐射增敏的可能性。研究结果不仅有助于阐明生物分子间的相互作用在细胞信号传导中的重要性，还能为肿瘤治疗提供新的选择途径。

ATR is an important protein kinase in cells responding to radiation stress. However,it is still unclear which microRNA involves in the regulation of ATR. In our previous work, it was found that miR-185 targeted ATR and increased the radiosensitivity of tumor cells. Based on these findings, point mutation, cell line with inducible miR-185 expression and inhibitors will be used to verify the targeted regulation of miR-185 on ATR and its downstream gene expressions. The role of ATR　in the generation of microRNAs will be investigated. The regulation network based on ATR responding to radiation will be optimized. Finally, the possibility of increasing radiosensitivity of tumor cells through down-regulation of ATR by miR-185 will be tested by cell and animal experiments. The obtained results not only elucidate the importance of biological molecular interaction in cellular signalling transduction, but also provide new possible option for cancer therapy.