硒蛋白SELENOI通过PI3K/AKT/mTOR信号通路促进胃癌增殖、迁移和侵袭
Selenoprotein SELENOI promotes the proliferation,migration and invasion of gastric cancer through the PI3K/AKT/mTOR signaling pathway
摘要
Abstract
Objective·To investigate the regulatory role of the selenoprotein SELENOI(ethanolamine phosphotransferase 1,EPT1)in the proliferation,migration and invasion of gastric cancer cells,as well as its molecular mechanism.Methods·The expression levels of SELENOI in gastric mucosal epithelial cells and gastric cancer cell lines were detected using Western blotting and quantitative real-time PCR(qPCR).The clinical pathological data of 100 patients who underwent surgery at the Department of Gastrointestinal Surgery of Renji Hospital,Shanghai Jiao Tong University School of Medicine,from 2010 to 2015 were collected,and the association between SELENOI expression levels and patient prognosis was analyzed.The expression of SELENOI in gastric adenocarcinoma tumor tissues and normal tissues was analyzed based on The Cancer Genome Atlas(TCGA)database.The differentially expressed genes between the SELENOI high-and low-expression groups were screened,and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis was performed to select SELENOI-related signaling pathways.The regulatory association of SELENOI with this pathway was verified by qPCR and Western blotting.HGC-27 and NUGC-3 gastric cancer cells were treated with SELENOI-targeted small interfering RNA(siRNA),SELENOI overexpression plasmid alone,or in combination with the mechanistic target of rapamycin(mTOR)inhibitor rapamycin.The cell proliferation ability was detected by CCK-8 assay,and cell migration and invasion abilities were detected by Transwell assay.Results·Bioinformatics analysis revealed that SELENOI was significantly highly expressed in gastric cancer tissues(P<0.05).Kaplan-Meier survival analysis of 100 patients with gastric adenocarcinoma showed that patients with high SELENOI expression had worse prognosis(P=0.022).qPCR and Western blotting results confirmed that the expression levels of SELENOI in HGC-27,NUGC-3,AGS,and MKN45 gastric cancer cell lines were significantly higher than those in gastric mucosal epithelial cells GES-1(all P<0.05).KEGG pathway enrichment analysis and subsequent molecular validation experiments confirmed that SELENOI promoted the activation of the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT)/mTOR signaling pathway in gastric cancer.CCK-8 and Transwell assay results showed that SELENOI enhanced the proliferation,migration and invasion abilities of gastric cancer cells by activating the PI3K/AKT/mTOR signaling pathway,and rapamycin significantly reversed this tumor-promoting effect.Conclusion·SELENOI is highly expressed in gastric cancer tissues and cells.SELENOI can promote the proliferation,migration and invasion of gastric cancer cells by activating the PI3K/AKT/mTOR signaling pathway.关键词
硒蛋白I/磷脂酰肌醇3-激酶/蛋白激酶B/哺乳动物雷帕霉素靶蛋白/胃癌Key words
SELENOI/phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT)/mechanistic target of rapamycin(mTOR)/gastric cancer分类
医药卫生引用本文复制引用
王铭杰,倪博,夏翔,张子臻..硒蛋白SELENOI通过PI3K/AKT/mTOR信号通路促进胃癌增殖、迁移和侵袭[J].上海交通大学学报（医学版）,2026,46(8):1015-1025,11.基金项目
国家自然科学基金(82103510,82303428,82473077,82473065) （82103510,82303428,82473077,82473065）
癌基因与相关基因国家重点实验室科研项目(课题)(KF2205-93) （课题）
上海市卫生健康委员会医学新技术研究与转化种子计划项目(2024ZZ2020) （2024ZZ2020）
上海市科学技术委员会三维电子腹腔内窥镜(微创外科领域)应用示范项目(25SF1905600) （微创外科领域）
中央高校基本科研业务费专项资金(YG2026ZD15) （YG2026ZD15）
仁济医院临床研究中心横向课题(IIT-2023-0001). National Natural Science Foundation of China(82103510,82303428,82473077,82473065) （IIT-2023-0001）
Research Project of the State Key Laboratory of Oncogenes and Related Genes(KF2205-93) （KF2205-93）
Medical New Technology Research and Translation Seed Program of the Shanghai Municipal Health Commission(2024ZZ2020) （2024ZZ2020）
Application Demonstration Project of Three-Dimensional Electronic Laparoscope in Minimally Invasive Surgery of the Science and Technology Commission of Shanghai Municipality(25SF1905600) （25SF1905600）
Fundamental Research Funds for the Central Universities(YG2026ZD15) （YG2026ZD15）
Horizontal Research Project of the Clinical Research Center,Renji Hospital(IIT-2023-0001). （IIT-2023-0001）
