M 6 A demethylase fat mass and obesity‐associated protein regulates cisplatin resistance of gastric cancer by modulating autophagy activation through ULK1

作者：Yan Zhang, Lingxi Gao, Wen Wang, Teng Zhang, Fangyi Dong, Wenping Ding · 发表于：Cancer Science · 年份：2022 · DOI：10.1111/cas.15469 · 被引用次数：54 · 研究领域：RNA modifications and cancer、Cancer-related molecular mechanisms research、Cancer-related gene regulation

Abstract Drug resistance is an important factor for treatment failure of gastric cancer. N 6 ‐methyladenosine (m 6 A) is the predominant mRNA internal modification in eukaryotes. The roles of m 6 A modification in drug resistance of gastric cancer remains unclear. In the present study, the m 6 A methylated RNA level was significantly decreased while the expression of m 6 A demethylase fat mass and obesity‐associated protein (FTO) was obviously elevated in cisplatin‐resistant (SGC‐7901/DDP) gastric cancer cells. Knockdown of FTO reversed cisplatin resistance of SGC‐7901/DDP cells both in vitro and in vivo, which was attributed to the inhibition of Unc‐51‐like kinase 1 (ULK1)‐mediated autophagy. Mechanistically, ULK1 expression was regulated in an FTO‐m 6 A‐dependent and YTHDF2‐mediated manner. Collectively, our findings indicate that the FTO/ULK1 axis exerts crucial roles in cisplatin resistance of gastric cancer.