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

Abstract

Abstract Objectives Cag A + Helicobacter pylori chronic infection cause malignant transformation of the human gastric mucosa. N6-methyladenosine (m 6 A) modifications are the most common and abundant mRNA modifications and one of the pathways affecting tumorigenicity and tumor progression. However, the role of m 6 A modification in the process of chronic H. pylori infection leading to malignant transformation of gastric mucosa is unclear. Methods In this study, we used Cag A − and Cag A + H. pylori chronic 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 m 6 A expression levels of GES-1 cells after chronic infection with Cag A − and Cag A + H. pylori were 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 m 6 A expression levels were further validated in clinical gastric cancer tissues. Results Chronic 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 m 6 A methylation modifications. Conclusions We verified the effect of chronic stimulation of Cag A + H. pylori on 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.

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