摘要
目的利用生物信息学对儿童暴发性心肌炎(fulminantmyocarditis,FM)患儿血清中差异表达的微RNA(microRNA,miRNA)及其靶基因进行分析,探索其发病机制。方法选择高通量公共基因表达数据库(Gene Expression Omnibus,GEO)中的数据集GSE221090,并利用GEO2R在线工具进行生物信息学分析,筛选出差异表达miRNA。利用在线miRDB数据库预测差异表达miRNA的靶基因。采用DAVID工具对筛选出的靶基因进行基因本体(gene ontology,GO)功能分析和京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)通路富集分析。通过STRING数据库和Cytoscape软件构建与差异表达基因相关联的蛋白质-蛋白质相互作用(protein-proteininteraction networks,PPI),并筛选出核心基因。结果对FM患儿与健康志愿者血清中差异表达miRNA进行筛选,共获得148个差异表达miRNA,其中上调109个、下调39个。上调mi RNA和下调miRNA各取评分排名前10位,利用在线miRDB数据库对上述miRNA进行靶基因预测,纳入表达上调miRNA所调控的靶基因291个,表达下调miRNA所调控的靶基因290个。对靶基因进行GO和KEGG分析,显示表达上调miRNA所调控的靶基因主要涉及磷脂酰肌醇3-激酶-蛋白激酶B(phosphatidylinositol 3-kinase/protein kinase B signaling pathway,PI3K/Akt)信号通路、叉头盒O信号通路等相关信号通路,表达下调miRNA所调控的靶基因主要涉及转化生长因子β(transforming growth factor-β,TGF-β)等相关信号通路。通过PPI和Cytoscape软件筛选出相关度评分排名前10位的差异表达基因:沉默调节蛋白1(sirtuin 1,SIRT1)、信号转导和转录激活因子3、雌激素受体1、H3.3组蛋白B、核受体共抑制因子1、干扰素调节因子4、白细胞介素-1β、Dicer1核糖核酸酶Ⅲ、组蛋白去乙酰化酶1(histone deacetylase 1,HDAC1)、DEAD盒解旋酶6。结论miR-22-3p、miR-4284等在儿童FM发病过程中发挥重要作用,可能与其调控的SIRT1和HDAC1表达水平相关,其机制可能通过PI3K/Akt、TGF-β等信号通路发挥生物学效应。
Objective To analyze the differentially expressed microRNA(miRNA)and their target genes in the serum of pediatric patients with fulminant myocarditis(FM)through bioinformatics methods,and to explore the pathogenesis.Methods GSE221090 dataset from the high-throughput Gene Expression Omnibus(GEO)were selected,and bioinformatics analysis was performed by using the GEO2R online tool to screen for differentially expressed miRNA.The online miRDB database was used to predict the target genes of the differentially expressed miRNA.The DAVID tool was employed for gene ontology(GO)enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis of the screened target genes.Additionally,protein-protein interaction networks(PPI)associated with the differentially expressed genes was constructed by using STRING database and Cytoscape software,and core genes were screened.Results A total of 148 differentially expressed miRNA were identified in the serum of pediatric FM group compared to normal children group,including 109 up-regulated and 39 down-regulated miRNA.The top ten up-regulated and down-regulated miRNA based on their scores were selected,and target gene prediction for a forementioned miRNA was conducted by using the online miRDB database,identifying 291 target genes regulated by up-regulted miRNA and 290 target genes regulated by down-regulated miRNA.Subsequent GO and KEGG analyses demonstrated that the target genes of up-regulated miRNA were primarily enriched in signaling pathways including phosphatidylinositol 3-kinase/protein kinase B signaling pathway(PI3K/Akt)and forhead box O,whereas the target genes of down-regulated miRNA predominantly participated in the transforming growth factor-β(TGF-β)signaling pathway and related pathways.The top ten differentially expressed genes with the highest relevance scores using PPI and Cytoscape software were identified,including sirtuin 1(SIRT1),signal transducer and activator of transcription 3,estrogen receptor 1,H3.3 histone B,nuclear receptor corepressor 1,interferon regulatory factor 4,interleukin-1 Beta,dicer 1 ribonucleaseⅢ,histone deacetylase 1(HDAC1),and DEAD-box helicase.Conclusion miR-22-3p,miR-4284,and others are crucial in the pathogenesis of pediatric FM,possibly related to the expression levels of SIRT1 and HDAC1 regulated,with mechanisms that may exert biological effects via the PI3K/Akt,TGF-β,and other signaling pathways.
作者
王陆银
姚家芳
唐坎凯
WANG Luyin;YAO Jiafang;TANG Kankai(Department of Critical Care Medicine,the First Affiliated Hospital of Huzhou Normal University,the First People’s Hospital of Huzhou,Huzhou 313000,Zhejiang,China;Department of Cardiology,the First Affiliated Hospital of Huzhou Normal University,the First People’s Hospital of Huzhou,Huzhou 313000,Zhejiang,China)
出处
《中国现代医生》
2025年第18期9-13,17,共6页
China Modern Doctor
基金
浙江省湖州市科学技术局项目(2024GYB24)。
