Silencing of MAT2A inhibits gastric cancer cell proliferation, migration, and invasion through activation of the p53 pathway

Objective: This study aimed to evaluate the effects of MAT2A silencing on the proliferation, migration, and invasion of gastric Cancer (GC) cells and to investigate the underlying molecular mechanisms.

Methods: MAT2A expression in GC tissues and adjacent normal tissues was assessed using immunohistochemistry and western blotting. Two GC cell lines with elevated MAT2A expression underwent gene silencing. Cellular proliferation, migration, and invasion were evaluated using EdU incorporation, Transwell, wound healing, and flow cytometry assays. Transcriptomic profiling was conducted to identify downstream pathways affected by MAT2A silencing, demonstrating significant enrichment of the p53 signaling pathway. To further clarify this mechanism, the p53 pathway was inhibited in MAT2A-silenced cells, and changes in p53 and p21 protein expression, along with alterations in proliferation, migration, and invasion, were reassessed.

Results: MAT2A expression was significantly higher in GC tissues and cell lines compared with adjacent normal controls. Silencing of MAT2A induced cell cycle arrest, suppressed proliferation and metastatic capacity, and enhanced Apoptosis, accompanied by an increased expression of p53 and p21 proteins. Inhibition of p53 with PFT-α reduced both p53 and p21 levels and reversed the suppressive effects of MAT2A silencing on GC cell proliferation, migration, and invasion.

Conclusion: MAT2A silencing induces cell cycle arrest, enhances Apoptosis, and inhibits malignant phenotypes of GC cells, including proliferation, migration, and invasion, through activation of the p53 signaling pathway.

Cell proliferation; Gastric cancer; MAT2A; Migration and invasion; P53 signaling pathway.