Rab25 acts as an oncogene and participates in the regulation of aerobic glycolysis via PKM2 in gastric adenocarcinoma

BACKGROUND: Rab25, a hub node of protein-protein interaction networks, has become one of the most popular tumor-associated proteins. Pyruvate kinase (PK) is the main rate-limiting enzyme in the glycolysis pathway and plays a significant role in the regulation of Warburg effect. In this study, we aimed to characterize the expression and function of Rab25 in gastric adenocarcinoma (GAC) and verify our hypothesis experimentally that Rab25 may participate in the regulation of aerobic glycolysis via PKM2 (a subtype of PK) in GAC. METHODS: The impact of Rab25 expression on patient overall survival was estimated using the Kaplan-Meier method. Rab25 expression was silenced or increased respectively by lentivirus-mediated transfection. To assess the role of Rab25 in cell viability in vitro, cell proliferation and migration experiments were performed. Levels of pyruvate and lactic acid were detected by kits. Immunofluorescence analysis and Co-Immunoprecipitation were performed to explore the interaction between Rab25 and PKM2 protein. RESULTS: High Rab25 expression was associated with reduced patient overall survival. Silencing Rab25 inhibits GAC cells proliferation and overexpressing Rab25 promotes cell proliferation and migration in gastric cells in vitro. The study revealed that Rab25 participates in the positive regulation of aerobic glycolysis in GAC cells. Rab25 protein and PKM2 protein co-located on the cell membrane and could bind to each other in GAC cells. Rab25 is a positive regulator of PKM2 and Rab25 up-regulation promotes phosphorylation of PKM2. CONCLUSIONS: In human GAC, Rab25 predicts poor prognosis and regulates aerobic glycolysis via phosphorylating PKM2-Y105.