FTO upregulation induced by MYC suppresses tumour progression in Epstein‒Barr virus-associated gastric cancer

作者：Yunyun Xu, Ting Li, Ao Shen, Xiaoqiong Bao, Jin‐Fei Lin, Li‐Zhen Guo, Qi Meng, Dan‐Yun Ruan, Qihua Zhang, Zhixiang Zuo, Zhao-Lei Zeng · 发表于：Research Square · 年份：2023 · DOI：10.21203/rs.3.rs-2593808/v1 · 被引用次数：1 · 研究领域：RNA modifications and cancer、Cancer-related molecular mechanisms research、Viral-associated cancers and disorders

Abstract Background: Epstein‒Barr virus-associated gastric cancer (EBVaGC) is regarded as a distinct molecular subtype of GC, accounting for approximately 9% of all GC cases, and it often exhibits unique molecular features and clinicopathological characteristics. Clinically, EBVaGC patients are found to have a significantly lower frequency of lymph node metastasis and better prognosis than uninfected individuals. RNA N6-methyladenosine (m6A) modification has an indispensable role in modulating tumour progression in various cancer types. However, its impact on EBVaGC remains unclear. Methods: Methylated RNA immunoprecipitation sequence (MeRIP-seq) and m6A dot blot were conducted to compare the m6A modification levels between EBVaGC and EBV-negative GC (EBVnGC) cells. Western blot, real-time quantitative PCR (RT-qPCR) and immunohistochemistry were applied to explore the underlying mechanism of the reduced m6A modification in EBVaGC. The biological function of FTO was determined in vivo and in vitro . The target genes of FTO were screened by MeRIP-seq, RT-qPCR and Western blot. The m6A binding proteins of target genes were verified by RNA pulldown and RNA immunoprecipitation assay. Chromatin immunoprecipitation and Luciferase report assay were performed to investigate the mechanism how EBV upregulated FTO expression. Results: Here, we found that m6A demethylase fat mass and obesity associated protein (FTO) was notably increased in EBVaGC, leading to a reduction in m6A modificati...