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首页|期刊导航|西安交通大学学报(医学版)|急性心肌梗死发病过程中miR-30a-5p的变化及其潜在的分子机制

急性心肌梗死发病过程中miR-30a-5p的变化及其潜在的分子机制OA北大核心CSTPCD

Changes of miR-30a-5p during the pathogenesis of acute myocardial infarction and its potential molecular mechanisms

中文摘要英文摘要

目的 评估miR-30a-5p作为急性心肌梗死(acute myocardial infarction,AMI)新诊断指标的潜力和潜在的分子机制.方法 下载GEO数据库中AMI相关microRNAs(miRNAs)和mRNA芯片数据集.qRT-PCR技术检测血清样本中miRNAs的水平,全自动生化仪检测其他的生化指标.受试者工作特征(ROC)曲线分析和Spearman相关性分析评估miR-30a-5p作为诊断AMI标志物的价值.R语言multiMiR包对miR-30a-5p的靶基因进行预测,STRING数据库构建蛋白相互作用网络,将结果导入Cytoscape3.7.1软件,筛选网络的中枢基因.R语言clusterProfiler包对中枢基因进行KEGG及GO分析,探索miR-30a-5p在AMI中的临床意义及其潜在的分子机制.结果 与对照组比较,AMI组患者血清中的miR-30a-5p上调,差异有统计学意义(P<0.05);miR-30a-5p与CK-MB、CK、TnT、proBNP和 CRP 水平呈正相关(rs=0.489,P<0.001;rs=0.347,P<0.001;rs=0.545,P<0.001;rs=0.533,P<0.001;rs=0.206,P<0.05),ROC曲线下面积(AUC)为0.862,灵敏度为84.4%,特异度为74.2%;2个数据集共得到差异表达基因(differentially expressed genes,DEGs)780个,miR-30a-5p的靶基因共1 061个,取交集共鉴定出61个共同基因.在PPI的中枢基因中BCL6、FOSL2、JDP2、LYN、PDE4D、SOCS3和SOX4得分较高且与AMI的发生密切相关;KEGG和GO富集分析显示,miR-30a-5p可能调节JAK-STAT、NF-kappaB及Wnt等信号通路参与炎症反应、细胞凋亡、自噬及心肌梗死后重塑等过程进而参与AMI的发生.结论 血清miR-30a-5p在AMI早期表达上调,对miR-30a-5p及其调控通路的研究,有助于诊断及治疗AMI.

Objective To evaluate the potential of miR-30a-5p as a novel indicator of acute myocardial infarction(AMI)and the underlying molecular mechanisms.Methods AMI-associated microRNAs(miRNAs)and mRNA microarray datasets were downloaded from the GEO database.Real-time fluorescence quantitative PCR(qRT-PCR)technique was used to detect the level of miRNAs in serum samples;automatic biochemistry was used to detect other biochemical indicators.Receiver operating characteristic(ROC)curve analysis and Spearson correlation analysis were performed to assess the value of miR-30a-5p as a diagnostic AMI marker.The target genes of miR-30a-5p were predicted with the R language multiMiR package,and the protein interaction network was constructed by the STRING database.The results were imported into Cytoscape 3.7.1 software to screen the pivotal genes of the network.The R language clusterProfiler package performed KEGG and GO analyses on the hub genes to explore the clinical significance of miR-30a-5p in AMI and its potential molecular mechanisms.Results Compared with the control group,miR-30a-5p was upregulated significantly in the serum of patients in the AMI group(P<0.05);miR-30a-5p was positively correlated with the levels of CK-MB,CK,TnT,proBNP and CRP(rs=0.489,P<0.001;rs=0.347,P<0.001;rs=0.545,P<0.001;rs=0.533,P<0.001;rs=0.206,P<0.05).The area under the ROC curve was 0.862,with sensitivity of 84.4%and specificity of 74.2%.A total of 780 differentially expressed genes(DEGs)were obtained from the two datasets.A total of 1 061 target genes of miR-30a-5p and 61 common genes were identified by taking the intersection set.Among the central genes of PPI,BCL6,FOSL2,JDP2,LYN,PDE4D,SOCS3 and SOX4 scored high and were closely associated with the occurrence of AMI.KEGG and GO enrichment analyses showed that miR-30a-5p might regulate JAK-STAT,NF-kappaB and Wnt signaling pathways,which were involved in inflammatory response,apoptosis,autophagy and post-infarction remodeling,and thus participated in the process of AMI.Conclusion Serum miR-30a-5p is up-regulated in the early stage of AMI,and the study on miR-30a-5p and its regulatory pathways can help with the diagnosis and treatment of myocardial infarction.

梁国新;郭畅;唐红悦;张明明

河北省人民医院临床医学研究中心,河北石家庄 050051||华北理工大学研究生学院,河北唐山 063000河北省人民医院临床医学研究中心,河北石家庄 050051||河北北方学院研究生学院,河北张家口 075000

临床医学

基因表达数据库(GEO)急性心肌梗死(AMI)microRNAs(miRNAs)生物信息学

Gene Expression Omnibus(GEO)acute myocardial infarction(AMI)microRNAs(miRNAs)bioinformatics

《西安交通大学学报(医学版)》 2024 (004)

567-574 / 8

2021年度河北省"三三三人才工程"资助项目(No.A202105015)Supported by the 2021 Hebei Province"Three Thirty-Three Talents Project"Funding Program(No.A202105015)

10.7652/jdyxb202404007

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