NRAGE是调控细胞功能的一个重要蛋白。一般认为NRAGE能够抑制肿瘤细胞增殖促进凋亡。但NRAGE在多数肿瘤中存在高表达的现象，表明可能具有原癌基因功能，这一矛盾构成NRAGE功能研究的困境。我们前期研究表明，食管癌组织中NRAGE表达水平是癌旁组织的3倍，该蛋白可以结合DNA损伤重组修复（Homologous recombination repair, HR）的核心蛋白Rad51,RNF8与Bard1，维持蛋白稳定，促进DNA损伤HR修复。因此提出假设，NRAGE通过促进HR修复保护基因组稳定，阻止细胞恶变；但在肿瘤细胞中，这种维持基因组稳定的作用也能够促进肿瘤对放化疗的抵抗。本项目将着重在课题组已有的NRAGE敲除小鼠模型中研究该基因促进DNA损伤重组修复的功能及其分子机制，以及促进食管癌抵抗放化疗的作用，为肿瘤耐药防治提供新的思路。

NRAGE is also known as MAGE-D1 or Dlxin-1, is a key protein regulating cell function. The general consensus is that NRAGE could inhibit the tumor cell proliferation and metastasis and apoptosis. But NRAGE has high expression in many kind of tumor tissues, suggestinga possible role of oncogene, constituting a dilemma of NRAGE function. Our preliminary study showed that the expression of NRAGE in esophageal cancer tissues is 3 times the level of matched adjacent tissues , and the coding protein can interact with DNA damage repair protein Rad51, RNF8 and Bard1, maintaining their protein levels, and promoting the repair of DNA damage. Therefore, we put forward the hypothesis, NRAGE play a double-edged sword function by promoting DNA repair, it maintains the genomic stability in normal cells, preventing the malignant transformation of cells; in tumor cells, it also maintains genomic stability, promoting resistance to chemotherapy. This project will focus on our NRAGE knockout mice to study the function and molecular mechanism of how NRAGE promotes DNA damage repair and resistance of radiotherapy and chemotherapy in esophageal cancer resistance，to provide new ideas for the prevention of tumors resistant.