高糖条件下Rab27a的O-GlcNAc化修饰参与介导子宫内膜癌细胞外泌体释放及相关机制研究

研究表明外泌体在子宫内膜癌的发生发展中起到重要作用，但是调控外泌体释放的相关机制目前尚不清楚。我们前期研究发现高糖引起的O-GlcNAc化水平增高促进子宫内膜癌细胞外泌体释放；进一步通过iTRAQ定量分析发现，升高O-GlcNAc化水平后多种外泌体释放相关调控蛋白表达增高，其中Rab27a升高最明显；同时研究发现Rab27a能够被O-GlcNAc化修饰。因此我们推测Rab27a的O-GlcNAc化修饰通过影响其表达水平调控细胞的外泌体释放。本课题拟从高糖与O-GlcNAc化修饰的关系、O-GlcNAc化修饰介导外泌体释放以及O-GlcNAc化修饰调控Rab27a表达的分子机制三个方面，探究高糖条件下O-GlcNAc化修饰调控子宫内膜癌细胞外泌体释放的相关机制。本课题有望揭示外泌体释放调控的新机制，为子宫内膜癌的发生发展提供新的理论和实验依据。

Previous studies have shown that exosomes play an important role in the occurrence and development of endometrial cancer, but the relevant mechanisms that regulate the release of exosomes are still unclear. In our previous research, we found that increased levels of O-GlcNAc caused by high glucose promoted the release of exosomes from endometrial cancer cells. Further, iTRAQ quautitative analysis revealed that, after the increase O-GlcNAc, the expression of some exosomes release-related proteins increased, among which Rab27a increased most significantly. At the same time, we found that Rab27a could be modified by O-GlcNAc. Therefore, we speculate that the O-GlcNAc modification of Rab27a regulates the release of exosomes by influencing its expression. In this study, we intend to explore the mechanism of O-GlcNAc-induced exosomes release in endometrial cancer cells from three aspects: the relationship between high glucose and O-GlcNAc modification, the mechanism of O-GlcNAc-induced exosomes release, and the mechanism of O-GlcNAc-induced Rab27a expression. This project is expected to reveal a new mechanism for the regulation of exosomes release and provide new theoretical and experimental basis for the occurrence and development of endometrial cancer.