基于外泌体中基因序列构建miRNA-mRNA预测复治肺结核特异的关键基因

Construction of key genes of miRNA-mRNA specific for predicting retreatment of tuberculosis based on gene sequences in exosomes

目的基于外泌体所建数据库构建复治肺结核(RTB)特异miRNA-mRNA的调控网络,为RTB在发病机制研究上提供理论支撑。方法利用初治肺结核(ATB)和RTB患者和健康对照者外周血进行外泌体数据库的建立,并筛选RTB特异的差异表达miRNA和差异表达mRNA,通过miRNet数据库预测差异表达miRNA在RTB特异性下游靶基因并进行富集分析。使用可视化软件Cytoscape绘制miRNA-mRNA调控网络图。结果ATB中有92个独立差异表达miRNA,RTB中有11个独立差异表达miRNA。ATB中有201个独立差异表达mRNA,RTB中有308个独立差异表达mRNA。对RTB特异性差异表达mRNA与RTB特异性差异表达miRNA预测的靶基因进行综合分析后取交集,共有8个靶向目标基因。PPI网络拓扑分析得出前20个关键基因,包括高表达RTB特异性差异表达基因miRNA的靶基因:PABPC1、EEF1A1、VCP、HNRNPA1;低表达RTB特异性差异表达基因miRNA的靶基因:DDX17、MAPK14、FLNA、TPT1、POLR2E。结论PABPC1、EEF1A1、VCP、HNRNPA1、DDX17、MAPK14、FLNA、TPT1、POLR2可能是RTB特异的关键基因,在疾病发展中扮演调控作用。

Objective To construct a regulatory network of specific miRNA-mRNA for the retreatment of tuberculosis(RTB)based on exosome database,and to provide theoretical support for the study of the pathogenesis of RTB.Methods Exosome database was established by using the peripheral blood of patients with initial differentially expressed miRNAs and differentially expressed mRNA were screened,and the differentially expressed miRNAs in RTB-specific downstream target genes were predicted and enriched by the miRNet database.The visualization software Cytoscape was used to draw the miRNA-mRNA regulation network diagram.Results There were 92 independent differentially expressed miRNA in ATB and 11 independent differentially expressed miRNA in RTB.There were 201 independent differentially expressed mRNA in ATB and 308 independent differentially expressed mRNA in RTB.The intersection of RTB-specific differentially expressed mRNA and RTB-specific differentially expressed miRNA prediction was comprehensively analyzed,and a total of 8 target genes were targeted.The top 20 key genes were analyzed by PPI network topology,including target genes of miRNA with high expression of RTB-specific differential expression genes miRNA:PABPC1,EEF1 A1,VCP,and HNRNPA1,and target genes with low expression of RTB-specific differential expression genes miRNA:DDX17,MAPK14,FLNA,TPT1 and POLR2 E.Conclusion PABPC1,EEF1 A1,VCP,HNRNPA1,DDX17,MAPK14,FLNA,TPT1 and POLR2 might be key genes specific to RTB and play a regulatory role in disease development.