AEG-1 3'UTR functions as a ceRNA to facilitate Helicobacter pylori-induced gastric cancer EMT by regulating the miR-375-3p/JAK2 axis.

Helicobacter pylori (H. pylori) infection is a major risk factor for gastric cancer (GC), but the molecular mechanisms driving H. pylori-induced gastric carcinogenesis remain incompletely understood. This study investigates the role of the AEG-1 3'-untranslated region (3'UTR) as a competitive endogenous RNA (ceRNA) in this process. A ceRNA network was constructed via whole-transcriptome sequencing of H. pylori-associated GC. Gain- and loss-of-function experiments were performed to assess the impact of the AEG-1 3'UTR on epithelial-mesenchymal transition (EMT) in infected GC cells. The regulatory mechanism was explored using bioinformatics, dual-luciferase reporter assays, and rescue experiments. In vivo effects were evaluated using AEG-1 knockout mouse models of H. pylori infection and nude mouse xenograft models. Results showed that AEG-1 and JAK2 were upregulated and miR-375-3p downregulated in H. pylori-infected GC cells and tissues. The AEG-1 3'UTR promoted proliferation, migration, invasion, and EMT by sponging miR-375-3p, thereby derepressing JAK2 and activating JAK2/STAT3 signaling. These oncogenic effects were reversed by JAK2 silencing or miR-375-3p overexpression. In AEG-1 knockout mice, H. pylori colonization and gastric inflammation were markedly reduced, accompanied by decreased expression of EMT and proliferation markers. Xenograft models further confirmed that the AEG-1/miR-375-3p/JAK2 axis drives GC growth and lung metastasis. These findings identify AEG-1 3'UTR as a ceRNA that regulates H. pylori-mediated EMT and carcinogenesis via the miR-375-3p/JAK2 axis, highlighting its potential as a therapeutic target.