REV7招募Aly调控热休克蛋白HSP70家族影响食管癌放射敏感性的机制研究

提高食管癌细胞的放射敏感性对降低食管癌的局部复发率具有重要意义。跨损伤DNA合成通路是复制后修复的一种重要机制。本项目组报道了这一通路关键分子REV7在食管癌组织中高表达，可调控受照射食管癌细胞凋亡。前期研究还发现REV7可招募mRNA核/质转运蛋白Aly入核，参与调控热休克蛋白Hsp70家族分子的表达。据此，本项目组提出科学假设：REV7招募Aly入核促进Hsp70家族分子pre-mRNA的剪接及核输出翻译，通过抑制多个细胞凋亡相关信号途径，从而增强食管癌细胞的辐射抗拒性。本项目拟通过多种分子生物学方法在前期研究基础上揭示：1）REV7招募Aly对Hsp70家族分子表达的影响及机制；2）Aly增强受照射食管癌细胞热休克反应抑制细胞凋亡引起食管癌细胞放射抗拒性的分子机制及逆转措施。本项目有望揭示REV7/Aly/Hsp70轴调控食管癌放射敏感性的新机制，为食管癌的放疗增敏提供新策略。

Exploration of effective method to enhance the radiosensitivity of esophageal cancer cells is significant to reduce the local recurrence rate of esophageal cancer. Translesion DNA synthesis pathway is an important pathway and involved in the mechanism of post-replication repair. We have previously reported that REV7, a key molecule of translesion DNA synthesis pathway, is highly expressed in esophageal cancer tissues, which could modulate the cell apoptosis of irradiated esophageal cancer cells. In our preliminary studies, we found that REV7 recruited mRNA nuclear/cytoplasm transportation protein Aly, which is involved in regulating the expression of heat shock protein Hsp70 family molecules. Accordingly, we put forward our scientific hypothesis: REV7 recruited Aly into the nucleus to promote the splicing of and the export of mature mRNA of Hsp70 family genes, thereby increasing the ability of heat shock of esophageal cancer cells and causing radiation resistance. Based on previous studies, this project aims to illustrate the following issues: 1) The mechanism of REV7 in promoting Hsp70 family member protein expression by recruiting Aly; 2) The effect of Aly on esophageal cancer radiosensitivity by enhancing heat shock ability. This project is expected to reveal a novel mechanism of radiosensitivity regulation of esophageal cancer cells from the perspective of REV7/Aly/Hsp70, and provide a new molecular target for the radiosensitivity enhancement of esophageal cancer.