环状RNA circSTX6编码的新蛋白circSTX6-144aa结合AnnexinA2/integrinα5促进鼻咽癌侵袭转移的机制研究

环状RNA在肿瘤发生发展过程中具有重要作用。我们通过分析RNA测序数据发现了一个新的环状RNA circSTX6。体内外实验证实circSTX6编码的蛋白circSTX6-144a.a.可以促进鼻咽癌细胞侵袭转移，并发现它可能通过结合Annexin A2/ integrin α5发挥作用。有趣的是，申请人发现circSTX6-144a.a.能够降低细胞硬度和粘附性。本项目的科学假说如下：circSTX6-144a.a.结合Annexin A2/integrin α5，干扰integrin α5内体循环，促使integrin α5在细胞膜上聚集，激活Integrin/FAK信号通路，导致细胞骨架重排和粘着斑降解，进而降低细胞硬度和粘附性，增强鼻咽癌细胞侵袭转移能力。本项目的完成将初步揭示circSTX6-144a.a.的生物学功能，并为将环状RNA编码的蛋白应用于鼻咽癌的诊疗打下理论基础。

Circular RNA (circRNAs) plays an important role in tumorigenesis and development. We found a new circular RNA circSTX6 by analyzing RNA sequencing data. In vitro and vivo experiments confirmed that circSTX6-144a.a. encoded by circSTX6 promoted invasive and metastasis of nasopharyngeal carcinoma cells and revealed that it may function by binding Annexin A2/ integrin α5. Interestingly, the applicant found that circSTX6-144a.a. can reduce cell stiffness and adhesion. The scientific hypothesis of this project is as follows: circSTX6-144a.a. binds Annexin A2/integrin α5, interferes with the integrin α5 endosomal cycle, drives integrin α5 to aggregate on the cell membrane, activates the Integrin/FAK signaling pathway, leads to cytoskeletal rearrangement and degradation of adherent patches, which in turn reduces cell stiffness and adhesion, and enhance the invasive and metastasis ability of nasopharyngeal carcinoma cells. The completion of this project will initially reveal the biological function of circSTX6-144a.a. and lay the theoretical foundation for the application of the protein encoded by circRNA to the diagnosis and treatment of nasopharyngeal carcinoma.