神经药理学报

神经药理学报 ›› 2022, Vol. 12 ›› Issue (4): 23-40.DOI: 10.3969/j.issn.2095-1396.2022.04.003

• 研究论文 • 上一篇    下一篇

外泌体ceRNA调控网络与阿尔茨海默病相关性的生物信息学分析

张志清，张永财，刘林轩，李壬清，刘济嘉，杜景考，姜北，魏会平，苏立宁   

  1. 河北北方学院基础医学院，张家口，075000，中国
  • 出版日期:2022-08-26 发布日期:2023-08-30
  • 通讯作者: 苏立宁，硕士研究生，副教授；研究方向：神经退行性疾病机制研究；E-mail:343376274@qq.com
  • 作者简介:张志清，18 级麻醉医学本科；研究方向：医学麻醉学；E-mail：zzq00112211@163.com.
  • 基金资助:
    2021 年省级大学生创新创业训练计划项目（No.S202110092003，No.S202110092004）；河北省教育厅青年项目（No.QN2019099）；河北省卫生厅重点科技研究计划（No.20200196）

Bioinformatics Analysis of the Relationship between Exosomal ceRNA Regulatory Network and Alzheimer’s Disease

ZHANG Zhi-qing，ZHANG Yong-cai，LIU Lin-xuan，LI Ren-qing，LIU Ji-jia，DU Jing-kao，JIANG Bei，WEI Huiping， SU Li-ning   

  1. Basic Medicine Department，Hebei North University，Zhangjiakou，075000，China
  • Online:2022-08-26 Published:2023-08-30

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摘要：

目的：探讨阿尔茨海默病（Alzheimer’s disease，AD）与外泌体ceRNA 调控网络之间的潜在关系，为临 床治疗及研究靶点提供基础。方法：在基因表达综合数据库（gene expression omnibus，GEO）中下载数据，筛选 AD 患者和健康对照之间的差异基因（differentially expressed genes，DEGs）和差异microRNAs（miRNAs），确 定AD 的生物标志物。利用DAVID 对DEGs 进行基因本体论（gene ontology，GO）功能富集分析，用KEGG 对 DEGs 进行信号通路分析，利用cytoscape 对DEGs 和靶向miRNAs 进行作用分析并找出关键节点。结果：筛选 到683 个DEGs（377 个下调的DEGs 和306 个上调的DEGs），并筛选了90 个与AD 相关的富集于外泌体和细 胞囊泡的DEGs 作为我们的目标DEGs。本项目还筛选了748 个差异表达的miRNAs（90 个下调的miRNAs 和 658 个上调的miRNAs），并筛选出186 个细胞外囊泡miRNAs（147 个上调的miRNAs 和39 个下调的miRNAs）。 利用数据库预测了这些miRNAs 与目标DEGs 之间的靶向关系、lncRNA 与miRNA 之间的靶向关系、circRNA 与miRNA 之间的靶向关系，构建了lncRNA-miRNA-mRNA 和circRNA-miRNA-mRNA ceRNA 调控网络， 重点探讨了部分结果在AD 疾病中的重要作用。结论：这些结果表明，AD 的发生是多个相互作用的基因和 非编码RNA 协同作用的结果。本项目数据的挖掘为AD 相关的外泌体ceRNA 网络提供了一个新的视角和 解析。

关键词: 阿尔茨海默病, 外泌体, mRNA, miRNA, lncRNA, circRNA, ceRNA

Abstract: Objective：Exploring the potential relationship between Alzheimer’s disease （AD） and exosomal ceRNA regulatory network to provide a basis for clinical treatment and research targets. Methods：Datas were downloaded in the Gene Expression Omnibus database （GEO）. Then the differentially expressed genes （DEGs） and differentially expressed miRNAs from AD patients and healthy controls were screened to identify biomarkers of AD. DAVID used to carry out functional enrichment analysis of gene ontology （GO）. Kyoto Encyclopedia of Genes and Genomes （KEGG） was used to performed signal pathway analysis on DEGs pathway analysis， Cytoscape was used to construct network between DEGs and differentially expressed miRNAs to identify key node genes. Results：683 DEGs （377 downregulated DEGs and 306 upregulated DEGs） were screened，and 90 AD related DEGs enriched in exosomes and cell vesicles were screened as our target DEGs. The study also screened 748 differentially expressed miRNAs （90 downregulated miRNAs and 658 upregulated miRNAs） and 186 extracellular vesicle miRNAs （147 upregulated miRNAs and 39 downregulated miRNAs）. The database was used to predict the targeting relationship between these miRNAs and target DEGs，the targeting relationship between lncRNA and miRNA，and the targeting relationship between circRNA and miRNA. The lncRNAmiRNA- mRNA and circRNA-miRNA-mRNA ceRNA regulatory networks were constructed， and the important role of some results in AD disease was emphatically discussed. Conclusion： These results indicated that the occurrence of AD is the result of the synergistic action of multiple interacting genes and non coding RNAs. The data of this study provides a new perspective and analysis for the exosomal ceRNA network related to AD.

Key words: Alzheimer’s disease, exosomes, mRNA, miRNA, lncRNA, circRNA, ceRNA