Role of YWHAG in cell proliferation in gastric cancer

Abstract

Abstract The role of tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein gamma (YWHAG) in gastric cancer (GC) remains unclear. In this study, we investigated its biological effects on GC as well as the associated molecular mechanisms. We evaluated YWHAG expression in GC and normal tissues, and using GC cells with YWHAG knockdown or overexpression, we examined GC cell viability and growth. We also performed experiments to determine GC cell cycle progression, apoptosis, migration, and invasion. We also verified the role of YWHAG in GC growth using a mouse xenograft tumor model and performed Gene Set Enrichment Analysis (GSEA) and western blot analysis to elucidate possible molecular mechanisms. Our results showed a significantly higher YWHAG expression level in GC tissues (p < 0.0001), especially in poorly differentiated GC tissues (p < 0.0001). Further, YWHAG knockdown significantly inhibited GC cell proliferation, migration, invasion, and epithelial-mesenchymal transformation; however, these effects were reversed via YWHAG overexpression. Furthermore, YWHAG downregulation significantly retarded the growth of xenograft tumors in mice, and mechanistically, YWHAG exerted oncogenic effects in GC by activating the PI3K/AKT pathway. Therefore, YWHAG promotes GC growth, functions as an oncogene, and has potential as a therapeutic target in GC.