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FTO-mediated m6A modification promotes malignant transformation of gastric mucosal epithelial cells in chronic Cag A+Helicobacter pylori infection.
- Source :
- Journal of Cancer Research & Clinical Oncology; Aug2023, Vol. 149 Issue 10, p7327-7340, 14p
- Publication Year :
- 2023
-
Abstract
- Objectives: Cag A<superscript>+</superscript>Helicobacter pylori chronic infection cause malignant transformation of the human gastric mucosa. N6-methyladenosine (m<superscript>6</superscript>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<superscript>6</superscript>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<superscript>−</superscript> and Cag A<superscript>+</superscript>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<superscript>6</superscript>A expression levels of GES-1 cells after chronic infection with Cag A<superscript>−</superscript> and Cag A<superscript>+</superscript>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<superscript>6</superscript>A expression levels were further validated in clinical gastric cancer tissues. Results: Chronic Cag A<superscript>+</superscript>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<superscript>6</superscript>A methylation modifications. Conclusions: We verified the effect of chronic stimulation of Cag A<superscript>+</superscript>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. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 01715216
- Volume :
- 149
- Issue :
- 10
- Database :
- Complementary Index
- Journal :
- Journal of Cancer Research & Clinical Oncology
- Publication Type :
- Academic Journal
- Accession number :
- 167362170
- Full Text :
- https://doi.org/10.1007/s00432-023-04684-4