基于生物信息学的心梗患者血小板中差异基因筛选及调控网络分析

Network analysis of screening and regulation of differentially expressed genes in platelets of patients with myocardial infarction based on bioinformatics

目的:构建急性心梗患者外周血血小板中核心miRNA调控网络,探讨外周血血小板相关miRNA在急性心梗的发生、发展中的作用。方法:利用miRNA以及mRNA表达谱芯片筛选出差异表达的miRNA和mRNA,采用FunRich 3.1.3软件预测差异表达miRNA的转录因子及靶基因,而后将预测的靶基因与基因芯片筛出的差异表达的基因取交集,使用Cytoscape软件构建miRNA‑mRNA调控网络,并对调控网络中的基因进行KEGG及GO分析。结果:通过基因表达谱数据共筛选到差异表达miRNA 27种,差异表达mRNA 2897个,预测到差异表达miRNA的靶基因共3563个,两者取交集与miRNA交叉匹配后共有503个miRNA‑mRNA调控关系,对调控关系中的靶基因进行KEGG富集及GO分析,结果显示这些靶基因主要涉及PI3K‑AKT信号通路、肌动蛋白细胞骨架的调节、MAPK信号通路、人乳头瘤病毒感染、Ras信号通路。GO分析主要分子功能包括蛋白质大分子衔接子活性、分子衔接子活性、DNA结合转录阻遏物活性等。结论:笔者分析了急性心梗人群与非心梗人群外周血血小板中miRNA‑mRNA调控网络及功能差异,进一步认识了血小板在急性心梗发生过程中的重要作用,加深了对急性心梗病理机制的理解。

Objective:To construct a core miRNA regulatory network in peripheral blood platelets of patients with acute myocardial infarction,and to explore the role of peripheral blood platelet-related miRNAs in the occurrence and development of acute myocardial infarction.Methods:miRNA and mRNA expression profiling chips were used to screen out differentially expressed miRNA and mRNA.FunRich 3.1.3 software was performed to predict the transcription factors and target genes of differentially expressed miRNA,and then the predicted target genes were intersected with the differentially expressed genes screened by the gene chip.Cytoscape software was applied to construct miRNA-mRNA regulatory network,and KEGG and GO analyses of genes were performed in the regulatory network.Results:A total of 27 differentially expressed miRNAs and 2897 differentially expressed mRNAs were screened through gene expression profiling data.A total of 3563 target genes for differentially expressed miRNAs were predicted,and they were intersected with the differentially expressed mRNAs.After a one-to-one correspondence,there were 503 miRNA-mRNA regulatory relationships.KEGG enrichment and GO analysis of the target genes in the regulatory network showed that these target genes were mainly involved in PI3K-AKT signaling pathway,regulation of actin cytoskeleton,MAPK signaling pathway,human papillomavirus infection,and Ras signaling pathway.GO analysis indicated that the main molecular functions of genes from network included protein macromolecule adaptor activity,molecular adaptor activity,DNA binding transcription repressor activity,etc.Conclusion:We analyze the miRNA-mRNA regulatory network and the different function in the platelets of acute myocardial infarction and non-infarction populations,and further understand the important role of platelets in the process of acute myocardial infarction,and deepen our understanding of the pathological mechanism of acute myocardial infarction.