晚期乳腺癌患者往往手术效果不佳，且丧失了内分泌或靶向治疗机会，多采用放射治疗，但辐射抵抗性是临床工作需要克服的问题。越来越多microRNA被证实能够增强肿瘤的放疗敏感性。课题组前期的研究显示miR-22能够增加体外乳腺癌细胞的放疗耐受性，并影响DNA损伤响应，但具体的机制尚不清楚。经过生物信息预测发现miR-22的潜在靶基因多富集在DSB修复通路上，而DSB修复能力直接影响细胞的放射敏感性。基于此，本项目拟从前期候选的miR-22靶基因中选取1-2种进行重点研究，确定其对于乳腺癌细胞放疗敏感性的影响，以及在DNA损伤响应中的作用，并在细胞和动物水平上研究miR-22及靶基因对于DSB修复途径的影响。本研究将从miR-22这个新视点为揭示乳腺癌放疗耐受的发生机制奠定基础，为提高局部晚期乳腺癌的放疗敏感性开创新的思路。

The radiation resistance of cancer cells needs to be overcome during the radio-therapy for breast cancer (BC) patients. Therefore, it is important to elucidate the factors that enhance the tumor radio-sensitivity. Significant of microRNA was found in regulation of tumor radiation. Our previous showed that inhibiting miR-22 could enhance the BC radio-sensitivity via regulation of DNA damage response (DDR), but the mechanism is not clear. In this study, we intend to focus on miR-22 target genes that may correlate with DDR, and validate whether they affect the radio-sensitivity in BC cell lines and mice. We further investigate whether these gene play important role in process of DNA damage repair. This project will first clarify the relationship between miR-22, DDR and radio-resistance, which could provide a new idea for the sensitization of breast cancer radiotherapy.