Published online Jul 15, 2024. doi: 10.4251/wjgo.v16.i7.3270
Revised: May 9, 2024
Accepted: May 20, 2024
Published online: July 15, 2024
Processing time: 124 Days and 4.9 Hours
Helicobacter pylori (H. pylori) colonizes the human gastric mucosa and is implicated in the development of gastric cancer (GC). The tumor microenvironment is ch
To explore the underlying mechanism of H. pylori-induced HIF-1α expression in promoting the malignant biological behavior of gastric epithelial cells (GES-1).
The study was conducted with human GES-1 cells in vitro. Relative protein levels of methyltransferase-like protein 14 (METTL14), HIF-1α, main proteins of the PI3K/AKT pathway, epithelial-mesenchymal transition (EMT) biomarkers, and invasion indicators were detected by Western blot. Relative mRNA levels of METTL14 and HIF-1α were detected by quantitative reverse transcription-poly
H. pylori promoted HIF-1α expression and activated the PI3K/AKT pathway. Notably, METTL14 was downregulated in H. pylori-infected gastric mucosal epithelial cells and positively regulated HIF-1α expression. Functional experiments showed that the overexpression of HIF-1α or knockdown of METTL14 enhanced the activity of the PI3K/AKT pathway, thereby driving a series of malignant transformation, such as EMT and cell proliferation, migration, and invasion. By contrast, the knockdown of HIF-1α or overexpression of METTL14 had an opposite effect.
H. pylori-induced underexpression of METTL14 promotes the translation of HIF-1α and accelerates tumor pro
Core Tip:Helicobacter pylori (H. pylori) is the most significant risk factor for gastric cancer. Studies have shown that hypoxia-inducible factor-1α (HIF-1α) is highly expressed in tumors, enabling them to adapt to hypoxic microenvironment and promoting malignant behavior. However, the pathogenesis of HIF-1α in H. pylori infection remains unclear. We found that methyltransferase-like protein 14 acts as a molecular switch of H. pylori-induced HIF-1α expression and regulates the malignant behavior of gastric epithelial cells through the PI3K/AKT pathway. This study is the first to explore the mecha