陶诗诗,陈 亮.新型内质网应激诱导蛋白 TRIM25 在乳腺癌细胞中的作用研究[J].集成技术,2020,(1):45-54
新型内质网应激诱导蛋白 TRIM25 在乳腺癌细胞中的作用研究
Role of a Novel Endoplasmic Reticulum Stress-Inducible Protein TRIM25in Breast Cancer Cells
  
DOI:10.12146/j.issn.2095-3135.20191028001
中文关键词:  TRIM25;乳腺癌;内质网应激;未折叠蛋白反应信号通路
英文关键词:TRIM25; breast cancer; endoplasmic reticulum stress; unfolded protein reaction signalingpathway
基金项目: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)
作者单位
陶诗诗 中国科学院深圳先进技术研究院 深圳 518055;中国科学院大学 北京 100049 
陈 亮 中国科学院深圳先进技术研究院 深圳 518055 
摘要点击次数: 324
全文下载次数: 446
中文摘要:
      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。
英文摘要:
      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.
查看全文  查看/发表评论  下载PDF阅读器
关闭
微信关注二维码 用微信扫一扫 用微信扫一扫 用微信扫一扫

美女

美女图片

美女

美女图片