Open AccessM 6 A demethylase fat mass and obesity‐associated protein regulates cisplatin resistance of gastric cancer by modulating autophagy activation through ULK1
Author(s) -
Zhang Yan,
Gao Lingxi,
Wang Wen,
Zhang Teng,
Dong Fangyi,
Ding Wenping
Publication year - 2022
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.15469
Subject(s) - cisplatin , gene knockdown , autophagy , demethylase , ulk1 , cancer , cancer research , cancer cell , chemistry , apoptosis , protein kinase a , biology , kinase , medicine , biochemistry , ampk , gene , chemotherapy , epigenetics
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.