新型内质网应激诱导蛋白 TRIM25 在乳腺癌细胞中的作用研究

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。

Role of a Novel Endoplasmic Reticulum Stress-Inducible Protein TRIM25in Breast Cancer Cells

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 novelinducible 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 ofTRIM25 knockdown on ER stress, unfolded protein reaction (UPR) signaling pathway and ER stress inducedapoptosis. Then, we detected expression of TRIM25 in different breast cells and analyzed the correlationbetween TRIM25 and prognosis of breast cancer patients by using bioinformatics. Our results identifiedthat ER stress significantly induce the expression of TRIM25. Moreover, TRIM25 knockdown promotesthe apoptosis of MCF7 cells through inducing ER stress and activating unfolded protein reaction signalingpathway. In addition, bioinformatics analysis shows that the expression of TRIM25 is up-regulated during thetransition from primary breast epithelial cells to breast cancer cells, and the high expression of TRIM25 alsosuggests poor prognosis in breast cancer patients.