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

OBJECTIVES

Cag A Helicobacter pylori chronic infection cause malignant transformation of the human gastric mucosa. N6-methyladenosine (mA) modifications are the most common and abundant mRNA modifications and one of the pathways affecting tumorigenicity and tumor progression. However, the role of mA 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 AH. 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 mA expression levels of GES-1 cells after chronic infection with Cag A and Cag AH. 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 mA expression levels were further validated in clinical gastric cancer tissues.

RESULTS

Chronic Cag AH. 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 mA methylation modifications.

CONCLUSIONS

We verified the effect of chronic stimulation of Cag AH. 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.