Helicobacter pylori promotes YTHDF2-mediated SRA1 m6A modification and promotes the occurrence and development of gastric cancer

Background Helicobacter pylori (H. pylori) is known to be linked to gastric cancer development, but its precise carcinogenic mechanisms are not fully understood. This study aims to investigate the function and mechanism of N6-methyladenosine (m6A) modification in H. pylori-associated gastric cancer, and to elucidate its regulatory network, offering novel insights and potential therapeutic targets for gastric cancer management. Methods Western blotting and quantitative PCR (q-PCR) will be used to assess the expression of YTH N6-methyladenosine RNA binding protein 2 (YTHDF2) and Steroid Receptor RNA Activator 1 (SRA1), and the impact of YTHDF2 overexpression/knockdown on SRA1 expression. The m6A MAZF enzyme digestion method, luciferase reporter assay, and RNA stability assay will be used to assess YTHDF2's role in H. pylori-mediated SRA1 upregulation through m6A modification. Results After H. pylori infection, SRA1 expression rises in mRNA and protein, boosting gastric mucosal and gastric cancer cell proliferation and migration, while YTHDF2 has an opposing impact. We demonstrate that H. pylori increases the m6A level of the SRA1 mRNA 3 ' untranslated regions by inhibiting the m6A reader protein YTHDF2, upregulates SRA1 expression, and activates the nuclear factor (NF)-kappa B pathway, thereby inducing malignant transformation in gastric mucosal epithelial cells and gastric cancer cells. Conclusion Our findings confirm that H. pylori upregulates SRA1 via m6A modification to enhance the malignant progression of gastric cancer, and provide important insights into the activation of the NF-kappa B pathway, which triggers the onset and progression of gastric cancer. This implies that SRA1 could be a promising therapeutic target for preventing gastric cancer.