摘要
内质网应激是当细胞受到缺氧或营养剥夺等外界因素刺激时而产生的一种效应,该效应与肿瘤细胞的存活息息相关。该研究揭示了TRIM25作为一种新型内质网应激诱导蛋白在肿瘤细胞中所发挥的作用,可为发现新的肿瘤靶点提供重要依据。该文以乳腺癌细胞MCF7为对象,先筛选构建了稳定敲低TRIM25的MCF7细胞系;然后,检测了TRIM25敲低对内质网应激、未折叠蛋白反应信号通路和内质网应激诱导的细胞凋亡的影响,以及TRIM25在不同乳腺细胞中的表达;最后,通过生物信息学分析TRIM25表达量与乳腺癌患者预后的相关性。结果显示,内质网应激会诱导TRIM25表达水平的大幅上升。通过敲低TRIM25可诱导内质网应激、激活未折叠蛋白反应信号通路从而显著促进乳腺癌细胞MCF7的凋亡。研究还发现,乳腺原发上皮细胞转化为乳腺癌细胞过程中伴随有TRIM25蛋白水平的上调,生物信息学分析也显示TRIM25在乳腺癌组织中高表达,并提示乳腺癌患者预后不良。
External stimuli such as hypoxia or nutritional deprivation may lead to endoplasmic reticulum(ER)stress which is closely related to the survival of cancer cells.In this study,we revealed that TRIM25,as a novel inducible protein during ER stress and its role in tumor cells,which provides evidences for new tumor targets.In this research,we constructed TRIM25 stable knockdown cell line in MCF7 and detected the effects of TRIM25 knockdown on ER stress,unfolded protein reaction(UPR)signaling pathway and ER stress induced apoptosis.Then,we detected expression of TRIM25 in different breast cells and analyzed the correlation between TRIM25 and prognosis of breast cancer patients by using bioinformatics.Our results identified that ER stress significantly induce the expression of TRIM25.Moreover,TRIM25 knockdown promotes the apoptosis of MCF7 cells through inducing ER stress and activating unfolded protein reaction signaling pathway.In addition,bioinformatics analysis shows that the expression of TRIM25 is up-regulated during the transition from primary breast epithelial cells to breast cancer cells,and the high expression of TRIM25 also suggests poor prognosis in breast cancer patients.
作者
陶诗诗
陈亮
TAO Shishi;CHEN Liang(Shenzhen Institutes of Advanced Technology,Chinese Academy of Sciences,Shenzhen 518055,China;University of Chinese Academy of Sciences,Beijing 100049,China)
出处
《集成技术》
2020年第1期45-54,共10页
Journal of Integration Technology
基金
国家自然科学青年基金项目(31801186)
中国科学院深圳先进技术研究院优秀青年基金项目(201801)
关键词
TRIM25
乳腺癌
内质网应激
未折叠蛋白反应信号通路
TRIM25
breast cancer
endoplasmic reticulum stress
unfolded protein reaction signaling pathway