文献类型：期刊文献

中文题名：肺缺血-再灌注核心基因介导的竞争性内源性RNA网络的构建

英文题名：Construction of competitive endogenous RNA network mediated by lung ischemia-reperfusion core genes

作者：李晓凤[1];唐明政[1];刘禧禧[1];宋子晴[1];张国欣[2];杨开银[3];张凌云[3]

第一作者：李晓凤

机构：[1]甘肃中医药大学第一临床医学院,兰州730000;[2]甘肃中医药大学基础医学院;[3]甘肃省中医院麻醉科

第一机构：甘肃中医药大学临床医学院

年份：2024

卷号：15

期号：1

起止页码：70

中文期刊名：器官移植

外文期刊名：Organ Transplantation

收录：CSTPCD;;北大核心:【北大核心2023】；CSCD:【CSCD2023_2024】；

基金：甘肃省自然科学基金(20JR5RA159);甘肃中医药大学2023年度研究生创新创业基金项目32号。

语种：中文

中文关键词：肺移植;缺血-再灌注损伤;核心基因;竞争性内源性RNA(ceRNA);微小RNA;长链非编码RNA;环状RNA;信号通路

外文关键词：Lung transplantation;Ischemia-reperfusion injury;Core gene;Competitive endogenous RNA(ceRNA);Micro RNA;Long non-coding RNA;Circular RNA;Signal pathway

摘要：目的分析肺缺血-再灌注损伤发生的核心基因并构建竞争性内源性RNA(ceRNA)网络。方法从基因表达综合(GEO)数据库下载GSE145989的原始数据当作训练集,GSE172222和GSE9634数据集作为验证集,并鉴定差异表达基因(DEG)。进行基因本体(GO)、京都基因与基因组百科全书(KEGG)富集分析。构建蛋白质-蛋白质相互作用(PPI)网络,筛选核心基因并分析核心基因的诊断价值、免疫细胞的免疫浸润水平。构建并验证ceRNA网络。分析基于ceRNA网络的靶向药物。结果共检测到179个DEG,其中61个下调基因,118个上调基因。GO分析结果显示,DEG与细胞迁移、分化和调节等生物学过程有关;与内吞囊泡膜、浆膜和膜筏等细胞成分有关;与趋化因子受体、G蛋白偶联受体、免疫受体活性和抗原结合等分子功能有关。KEGG分析显示DEG参与肿瘤坏死因子(TNF)、Wnt、白细胞介素(IL)-17和核因子(NF)-κB等信号通路。PPI网络提示CD8A、IL2RG、STAT1、CD3G和SYK是肺缺血-再灌注损伤的核心基因。ceRNA网络提示miR-146a-3p、miR-28-5p和miR-593-3p与CD3G的表达相关;miR-149-3p、miR-342-5p、miR-873-5p和miR-491-5p与IL2RG表达相关;miR-194-3p、miR-512-3p、miR-377-3p和miR-590-3p与SYK表达相关;miR-590-3p和miR-875-3p与CD8A表达相关;miR-143-5p、miR-1231、miR-590-3p、miR-875-3p与STAT1表达相关。CD3G有13种靶向药物,IL2RG有4种靶向药物,SYK有28种靶向药物,lncRNA MUC2有3种靶向药物,未发现CD8A、STAT1和其他ceRNA网络基因的靶向药物。结论CD8A、IL2RG、STAT1、CD3G和SYK是肺缺血-再灌注损伤的核心基因,对核心基因进行研究分析可能有助于肺缺血-再灌注损伤的诊断,并提供新的研究思路和治疗靶点。
Objective To analyze the core genes of lung ischemia-reperfusion injury and construct a competitive endogenous RNA(ceRNA)network.Methods Original data of GSE145989 were downloaded from the Gene Expression Omnibus(GEO)database as the training set,and the GSE172222 and GSE9634 datasets were used as the validation sets,and the differentially-expressed genes(DEG)were identified.Gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were performed.Protein-protein interaction(PPI)network was constructed,and the core genes were screened,and the diagnostic values of these core genes and the immune infiltration levels of immune cells were evaluated.The ceRNA network was constructed and validated.The targeted drugs based on ceRNA network were assessed.Results A total of 179 DEG were identified,including 61 down-regulated and 118 up-regulated genes.GO analysis showed that DEGs were associated with multiple biological processes,such as cell migration,differentiation and regulation,etc.They were correlated with cell components,such as vesicle membrane,serosa and membrane raft,etc.They were also associated with multiple molecular functions,such as chemokine receptor,G protein-coupled receptor,immune receptor activity and antigen binding,etc.KEGG pathway enrichment analysis revealed that DEG were involved in tumor necrosis factor(TNF),Wnt,interleukin(IL)-17 and nuclear factor(NF)-κB signaling pathways,etc.PPI network suggested that CD8A,IL2RG,STAT1,CD3G and SYK were the core genes of lung ischemia-reperfusion injury.The ceRNA network prompted that miR-146a-3p,miR-28-5p and miR-593-3p were related to the expression level of CD3G.The miR-149-3p,miR-342-5p,miR-873-5p and miR-491-5p were correlated with the expression level of IL-2RG.The miR-194-3p,miR-512-3p,miR-377-3p and miR-590-3p were associated with the expression level of SYK.The miR-590-3p and miR-875-3p were related to the expression level of CD8A.The miR-143-5p,miR-1231,miR-590-3p and miR-875-3p were associated with the expression level of STAT1.There were 13 targeted drugs for CD3G,4 targeted drugs for IL-2RG,28 targeted drugs for SYK and 3 targeted drugs for lncRNA MUC2.No targeted drugs were identified for CD8A,STAT1 and other ceRNA network genes.Conclusions CD8A,IL2RG,STAT1,CD3G and SYK are the core genes of lung ischemia-reperfusion injury.The research and analysis of these core genes probably contribute to the diagnosis of lung ischemia-reperfusion injury and providing novel research ideas and therapeutic targets.