解放军医学院学报2024,Vol.45Issue(3):270-275,6.DOI:10.12435/j.issn.2095-5227.2024.015
E6AP通过调节糖酵解促进胃癌细胞增殖和迁移的机制研究
Mechanism of E6AP in promoting gastric cancer cell proliferation and migration by regulating glycolysis
摘要
Abstract
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.关键词
胃癌/E3泛素连接酶E6相关蛋白/细胞增殖/细胞迁移/有氧糖酵解Key words
gastric cancer/E3 ubiquitin ligase E6-associated protein/cell proliferation/cell migration/glycolysis分类
医药卫生引用本文复制引用
高兢望,曹博,徐其轩,赵瑞阳,李航航,张寰,卫勃..E6AP通过调节糖酵解促进胃癌细胞增殖和迁移的机制研究[J].解放军医学院学报,2024,45(3):270-275,6.基金项目
国家自然科学基金面上项目(82273231) (82273231)