Abstract
Drug resistance is an important factor for treatment failure of gastric cancer. N6 -methyladenosine (m6 A) is the predominant mRNA internal modification in eukaryotes. The roles of m6 A modification in drug resistance of gastric cancer remains unclear. In the present study, the m6 A methylated RNA level was significantly decreased while the expression of m6 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-m6 A-dependent and YTHDF2-mediated manner. Collectively, our findings indicate that the FTO/ULK1 axis exerts crucial roles in cisplatin resistance of gastric cancer.
Keywords:
FTO; ULK1; autophagy; cisplatin resistance; gastric cancer.