E6AP通过调节糖酵解促进胃癌细胞增殖和迁移的机制研究OACSTPCD

Background Rapid proliferation of cancer cells and distant metastasis are the main causes of death in gastric cancer patients.Exploring the mechanism of gastric cancer development and finding novel diagnostic and therapeutic targets are the urgent problems to be solved nowadays.Objective To investigate the effects of E3 ubiquitin ligase E6-associated protein(E6AP)on the proliferation,migration,and aerobic glycolytic capacity of gastric cancer cells.Methods Immunohistochemistry was used to detect the expression of E6AP in gastric cancer tissues and paracancerous tissues.The relationship between the expression of E6AP and the prognosis of gastric cancer patients was analyzed,the expression of E6AP in gastric cancer cell lines and normal gastric mucosal epithelial cell lines was detected by Western blot,and the expression of HK2,ENO1 and other glycolysis-related proteins in gastric cancer cells was detected.The proliferation and migration abilities of cells were examined by the 5-Ethynyl-2'-deoxyuridine(EdU)assay and Transwell assay,respectively;and the aerobic glycolysis ability of gastric cancer cells was reflected by the glycolysis-related assays.Results The expression of E6AP in gastric cancer tissues was significantly higher than its expression in paracancerous tissues(P<0.05).Western blot and glycolysis-related assays showed that lactate level,pyruvate level,ATP level,and glucose uptake rate of gastric cancer cells in the sh-E6AP group were significantly lower compared with that of NC-E6AP(P<0.05).EdU and Transwell assays showed that the proliferation and migration ability of cells in sh-E6AP group was significantly lower than that of cells in NC-E6AP group(P<0.05).Conclusion E6AP is highly expressed in gastric cancer tissues,and it enhances the proliferation and migration of gastric cancer cells by increasing their aerobic glycolysis level.E6AP may be a novel molecular marker and therapeutic target to predict the prognosis of gastric cancer patients.