摘要
目的:本研究旨在通过生物信息学方法系统分析肌醇需求酶1(Inositol-Requiring Enzyme 1,IRE1)、蛋白激酶R样内质网激酶(Protein Kinase R-like Endoplasmic Reticulum Kinase,PERK)、激活转录因子6(Activating Transcription Factor 6,ATF6)在舌鳞癌中的表达及意义。方法:使用GEO、Kaplan-Meier Plotter、GeneMANIA、DAVID等多个数据库对IRE1、PERK、ATF6在舌鳞癌中的表达与预后价值、相互蛋白作用网络及功能富集进行综合分析。结果:ATF6在舌鳞癌组织中表达高于癌旁正常组织,差异具有统计学意义(P <0.05)。IRE1及PERK高表达组患者总生存率(OS)高于低表达组,ATF6高表达组患者OS低于低表达组,差异均具有统计学意义(P <0.05)。本研究筛选出与IRE1、PERK、ATF6相互作用的蛋白质各20个并进行GO富集分析。IRE1及相关蛋白富集于内质网、线粒体等细胞组分中,具有蛋白质结合、蛋白磷酸酶结合等分子功能,参与内质网应激反应、泛素依赖性ERAD途径等生物学过程。PERK及相关蛋白富集于胞液、细胞膜等细胞组分中,具有翻译起始因子活性、RNA结合等分子功能,参与内质网未折叠蛋白反应、细胞对葡萄糖饥饿的反应等生物学过程。ATF6及其相关蛋白富集于内质网、细胞核等细胞组分中,具有转录调控区序列特异性DNA结合、蛋白质异二聚化活性等分子功能,参与RNA聚合酶Ⅱ启动子转录的正调控、内质网未折叠蛋白反应等生物学过程。结论:ATF6在舌鳞癌组织中呈现高表达,同IRE1、PERK与舌鳞癌患者不良预后相关。在未来抗肿瘤治疗中,IRE1、PERK、ATF6可能成为舌鳞癌的诊断和治疗的新选择。
Objective:The aim of this study is to systematically analyse the expression and significance of inositolrequiring enzyme 1(IRE1),protein kinase R-like endoplasmic reticulum kinase(PERK)and activating transcription factor 6(ATF6)in squamous carcinoma of the tongue by bioinformatics methods.Methods:A comprehensive analysis of the expression and prognostic value,mutual protein interaction network and functional enrichment of IRE1,PERK and ATF6 in tongue squamous carcinoma is performed using multiple databases such as GEO,Kaplan-Meier Plotter,GeneMANIA and DAVID.Results:The expression of ATF6 in tongue squamous cell carcinoma tissues is higher than that in adjacent normal tissues,the difference is statistically significant(P<0.05).The overall survival rate(OS)of patients with IRE1 and PERK high expression group is higher than that of low expression group,and the OS of patients with ATF6 high expression group is lower than that of low expression group,with statistical significance(P<0.05).In this study, 20 proteins interacting with IRE1, PERK and ATF6 are selected and analyzed with GO enrichment. IRE1 and its related proteins are enriched in endoplasmic reticulum, mitochondria and other cell components, and have molecular functions such as protein binding and protein phosphatase binding, participating in biological processes such as response to endoplasmic reticulum stress and ubiquitin-dependent ERAD pathway. PERK and its related proteins are enriched in cellular components such as cytoplasm and cell membrane, and possess molecular functions such as translation initiation factor activity and RNA binding, involved in endoplasmic reticulum unfolded protein response, cellular response to glucose starvation starvation and other biological processes. ATF6 and its related proteins are enriched in endoplasmic reticulum, nucleus and other cell components. It has transcription regulatory region sequence-specific DNA binding and protein heterodimerization activity and other molecular functions, involved in the positive regulat
作者
张勇涛
李霞
李晓齐
买丽亚木古丽·阿布都克尤木
张贵程
齐鲁
ZHANG Yongtao;LI Xia;LI Xiaoqi;Maryamgul·Abdukiyum;ZHANG Guicheng;QI Lu(Second Clinical College,Xinjiang Medical University,Urumqi 830092,China)
出处
《生物化工》
CAS
2023年第5期1-6,18,共7页
Biological Chemical Engineering
基金
新疆医科大学校级大学生创新创业资助项目(CX2021011)。
