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  • 国家药监局综合司 国家卫生健康委办公厅

儿童暴发性心肌炎miRNA的筛选及生物信息学分析

通讯作者: 王陆银, 13857271931@163.com
DOI:10.12201/bmr.202503.00064
声明:预印本系统所发表的论文仅用于最新科研成果的交流与共享,未经同行评议,因此不建议直接应用于指导临床实践。

Screening and Bioinformatics Analysis of Differentially Expressed miRNAs in Pediatric Fulminant Myocarditis

  • 摘要:摘要 目的 利用生物信息学对儿童暴发性心肌炎患者血清中差异表达的微小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miRNAs。利用在线miRDB数据库预测差异表达miRNAs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相互作用网络(protein-protein interaction networks,PPI),并筛选出核心基因。结果 对儿童暴发性心肌炎(fulminant myocarditis,FM)患者组与正常儿童组血清中差异表达miRNAs进行筛选,共获得148个差异表达miRNAs,其中上调109个、下调39个。上调miRNAs和下调miRNAs各取评分前十位,利用在线miRDB数据库对上述miRNAs进行靶基因预测,纳入表达上调的miRNA所调控的靶基因291个,表达下调的miRNA所调控的靶基因290个。对靶基因进行GO和KEGG分析,显示表达上调的miRNA所调控的靶基因主要涉及PI3K-Akt信号通路、FoxO信号通路等相关信号通路,表达下调的miRNA所调控的靶基因主要涉及TGF-β等相关信号通路。通过PPI 和Cytoscape 软件筛选出相关度评分前十位的差异表达基因,包括SIRT1、STAT3、ESR1、H3-3B、NCOR1、IRF4、IL1B、DICER1、HDAC1、DDX6。结论 miR-22-3p、miR-4284等在儿童FM发病过程中发挥重要的作用,可能与其调控的SIRT1和HDAC1的表达水平相关,其机制可能通过PI3K-Akt、TGF-β等信号通路来发挥生物学效应。

    关键词: 暴发性心肌炎;基因芯片;生物信息学

     

    Abstract: Abstract Objective To analyze the differentially expressed miRNAs and their target genes in the serum of pediatric patients with fulminant myocarditis through bioinformatics methods, and to explore the pathogenesis. Methods We selected the GSE221090 dataset from the Gene Expression Omnibus (GEO) high-throughput gene expression database, and bio-informatics analysis was performed using the GEO2R online tool to screen for differentially expressed miRNAs. The online miRDB database was used to predict the target genes of the differentially expressed miRNAs. The DAVID tool was employed for GO enrichment analysis and KEGG pathway analysis of the screened target genes. Additionally, a protein-protein interaction network (PPI) associated with the differentially expressed genes was constructed using the STRING database and Cytoscape software, and core genes were screened. Results A total of 148 differentially expressed miRNAs were identified in the serum of the pediatric fulminant myocarditis group compared to a control group of normal children,including 109 up-regulated and 39 down-regulated miRNAs. We selected the top ten up-regulated and down-regulated miRNAs based on their scores, and target gene prediction for the aforementioned miRNAs was conducted using the online miRDB database, identifying 291 target genes regulated by up-regulted miRNAs and 290 target genes regulated by down-regulated miRNAs. Subsequent GO and KEGG analyses demonstrated that the target genes of up-regulated miRNAs were primarily enriched in signaling pathways including PI3K-Akt and FoxO, whereas the target genes of down-regulated miRNAs predominantly participated in the TGF-β signaling pathway and related pathways. We identified the top ten differentially expressed genes with the highest relevance scores using PPI and Cytoscape software, including SIRT1, STAT3, ESR1, H3-3B, NCOR1, IRF4, IL1B, DICER1, HDAC1, and DDX6. Conclusion MiR-22-3p, miR-4284, and others are crucial in the pathogenesis of pediatric fulminant myocarditis, possibly related to the expression levels of SIRT1 and HDAC1 they regulate, with mechanisms that may exert biological effects via the PI3K-Akt, TGF-β, and other signaling pathways.

    Key words: Fulminant myocarditis; Gene chip; Bioinformatics

    提交时间:2025-03-21

    版权声明:作者本人独立拥有该论文的版权,预印本系统仅拥有论文的永久保存权利。任何人未经允许不得重复使用。
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    1 2025-02-17

    bmr.202503.00064V1

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王陆银. 儿童暴发性心肌炎miRNA的筛选及生物信息学分析. 2025. biomedRxiv.202503.00064

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