METTL17 promotes gastric cancer progression by activating the Wnt/β-catenin signaling pathway through negative regulation of GSK-3β

Purpose Gastric cancer is a highly prevalent malignancy associated with extremely poor prognosis. METTL17, a mitochondrial protein belonging to the methyltransferase-like family, has been shown to drive the progression of several cancers including colorectal and oral cancers, yet its role in gastric cancer remains unexplored. This study sought to characterize the expression profile, biological functions, and underlying regulatory mechanisms of METTL17 in gastric cancer. Methods In this study, bioinformatics analysis, tissue microarray immunohistochemistry, and Western blot were performed to determine the expression levels of METTL17 in gastric cancer cells and tissues and to assess its clinical relevance. In vitro and in vivo functional assays were conducted to investigate the effects of METTL17 on the proliferation, migration, invasion, and tumorigenic potential of gastric cancer cells. Quantitative proteomics and Western blot were further applied to screen and validate the downstream signaling pathways regulated by METTL17. Results METTL17 was significantly upregulated in gastric cancer and correlated with poor prognosis in affected patients. Functional assays demonstrated that knockdown of METTL17 suppressed the proliferation, migration, invasion, and in vivo tumorigenic capacity of gastric cancer cells, whereas overexpression of METTL17 yielded the opposite effects. Mechanistically, quantitative proteomic profiling and Western blot analysis showed that METTL17 negatively regulates GSK-3β expression, thereby activating the Wnt/β-catenin signaling pathway. Conclusion METTL17 promotes malignant progression of gastric cancer by repressing GSK-3β expression and consequently activating the Wnt/β-catenin signaling pathway. Our findings provide novel insights into the diagnosis and treatment of gastric cancer.