摘要
目的 分析及验证ISL1基因在心肌梗死中的表达,挖掘其在心肌梗死中的作用机制.方法 通过对GEO数据库中芯片表达谱数据进行分析找到ISL1基因在心肌梗死中的表达特征,以及ISL1基因高度共表达的相关基因及富集的通路功能,纳入急性心肌梗死患者及其健康对照,采用RT-PCR方法验证ISL1、GRIN2D等基因的表达.结果 ISL1基因在心肌梗死样本的表达量高于对照组样本.GSE59867和GSE29111两个数据集中,top2000、top2500、top3000的相关性基因交集分别共有152个、231个、329个.共表达基因功能注释交集基因发现,交集基因与胚胎时期器官发生发育、基质蛋白的形成、上皮细胞的分化以及相关信号通路的活动密切相关.最后,ISL1相关ceRNA调控网络构建中,有12个基因位于ISL1 top2000的相关性交集中,与miRNA共参与形成21对miRNA-mRNA.并且通过多个队列找出其关键的调控基因为GRIN2D,该基因与ISL1竞争性结合多个miRNA且表达量在两个独立数据集中呈现高度负相关(r=-0.52,-0.41).RT-PCR结果发现急性心肌梗死组miR-128-3p、miR-27a-3p、miR-27b-3p表达水平低于对照组,ISL1、GRIN2D表达水平高于对照组(均P＜0.01).结论 ISL1可能通过参与基质蛋白的形成、上皮细胞的分化以及相关信号通路的活动,对心肌梗死发挥保护作用.
Abstract
Objective To analyze and verify the expression of ISL1 gene in myocardial infarction,and explore its mechanism of action in myocardial infarction.Methods By analyzing the chip expression profile data in the GEO database,the expression characteristics of the ISL1 gene in myocardial infarction,as well as the highly co expressed related genes and enriched pathway functions of the ISL1 gene,were identified.Patients with myocardial infarction and their healthy controls were included,and the expression of genes such as ISL1 and GRIN2D was verified using real-time polymerase chain reaction(RT-PCR).Results The expression level of ISL1 gene in myocardial infarction samples was higher than that in the control group samples.In the GSE59867 and GSE29111 datasets;there are a total of 152,231,and 329 intersections of the top 2000,top 2500,and top 3000 related genes,respectively.The functional annotation of co-expressed genes revealed that intersection genes were closely related to organ development,matrix protein formation,epithelial cell differentiation,and the activity of related signaling pathways during embryonic development.Finally,in the construction of the ISL1 related ceRNA regulatory network,12 genes were located in the ISL1 top 2000 related mating set,and together with miRNAs,they participated in the formation of 21 pairs of miRNA-mRNA.And through multiple queues,the key regulatory gene was identified as GRIN2D,which competitively bound to multiple miRNAs with ISL1 and its expression was highly negatively correlated with ISL1 in two independent datassets(r=-0.52,-0.41).The RT-PCR results showed that the expression levels of miR-128-3p,miR 27a-3p,and miR-27b-3p in the acute myocardial infarction group were lower than those in the control group,while the expression levels of ISL1 and GRIN2D were higher than those in the control group(all P＜0.01).Conclusions ISL1 may play a protective role in myocardial infarction by participating in the formation of matrix proteins,differentiation of epithelial cells,and activity of related signaling pathways.
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