FTO-mediated m6A modification promotes malignant transformation of gastric mucosal epithelial cells in chronic Cag A+ Helicobacter pylori infection

Abstract

AbstractObjectivesCag A+Helicobacter pylorichronic infection cause malignant transformation of the human gastric mucosa. N6-methyladenosine (m6A) modifications are the most common and abundant mRNA modifications and one of the pathways affecting tumorigenicity and tumor progression. However, the role of m6A modification in the process of chronicH. pyloriinfection leading to malignant transformation of gastric mucosa is unclear.MethodsIn this study, we used Cag A−and Cag A+H. pylorichronic infection to establish cellular models in GES-1 cells and analyzed the cellular morphology, proliferation, apoptosis, invasiveness and tumorigenicity of gastric mucosal epithelial cells. The m6A expression levels of GES-1 cells after chronic infection with Cag A−and Cag A+H. pyloriwere examined, and modifying effect of FTO (the fat mass and obesity-associated protein) on CD44 was verified by MeRIP–qPCR. Finally, the FTO expression changes and m6A expression levels were further validated in clinical gastric cancer tissues.ResultsChronic Cag A+H. pylori-infected GES-1 cells exhibit altered cell morphology, apoptosis inhibition, abnormal proliferation, enhanced migration, colony formation, and increased stem cell-like properties. Meanwhile, FTO and CD44 expression was enhanced, and FTO may induce malignant transformation of gastric mucosa by regulating CD44 mRNA m6A methylation modifications.ConclusionsWe verified the effect of chronic stimulation of Cag A+H. pylorion malignant transformation of gastric mucosal epithelium. revealing the possibility of FTO in promoting malignant transformation of gastric mucosa by modifying CD44 mRNA methylation, suggesting that FTO expression is a potential molecule for malignant transformation of gastric mucosal epithelial cells.