N6-Methyladenosine（m6A）修饰在病毒感染复制及肿瘤进展起重要作用。EBV感染及潜伏促进鼻咽癌发生发展，但m6A修饰对EBV感染及鼻咽癌的作用与机制不清。课题组前期发现m6A识别蛋白YTHDF1在鼻咽癌中高表达并与患者预后不良相关；沉默或敲除YTHDF1可促进EBV复制激活因子BRLF1、BZLF1及核酸复制关键基因EBNA1的表达及病毒复制，MeRIP-seq分析EBV部分基因可以被m6A修饰，质谱发现YTHDF1与促RNA降解蛋白RNA解旋酶DDX17结合，沉默DDX17可促进EBV的激活和复制。推测YTHDF1通过识别病毒RNA m6A修饰并促进其降解而维持鼻咽癌中EBV基因组及其表达的稳态，从而促进鼻咽癌进展。本项目将深入探讨病毒RNA m6A修饰及其在EBV潜伏和致癌中的作用和机制，阐明YTHDF1介导RNA降解新机制及致癌机制，为发现鼻咽癌防控新靶点奠定基础。

N6-Methyladenosine (m6A) modification in RNAs plays critical roles in virus infection and replication, and cancer development and progression. EBV latent infection promotes nasopharyngeal carcinoma (NPC) progression, but whether m6A modification plays roles in EBV infection and NPC progression is not clear. We found higher expression of m6A recognized protein YTHDF1 was related with worse prognosis of NPC patients, and knocking down YTHDF1 promoted the expression of EBV immediate-early genes (BRLF1 and BZLF1) and EBV genome replication gene EBNA1 and virus replication. MeRIP-seq data found EBV genes, such as BRLF1, BZLF1 and EBNA1, could be m6A-modified. Co-Immunoprecipitation and Mass spectrum found YTHDF1 could interact with RNA helicase DDX17, which promoted RNA degradation. Knocking down DDX17 promoted EBV re-activation and replication. Therefore, we speculate that YTHDF1 recognizes m6A-modified RNA of EBV genes for degradation, thus maintaining EBV homeostasis in NPC and further promoting NPC progression. Thus, in this proposal, we aim to illuminate the relationship of m6A modification of EBV expressed mRNAs, EBV infection and NPC tumorigenesis. Besides, we hope to investigate the novel mechanisms of YTHDF1 in the promotion of RNA degradation and NPC progression, and to identify a potential diagnostic and therapeutic target for NPC.