基于生物信息学的椎间盘退变miRNA-mRNA调控关系的分析  

Analysis of miRNA-mRNA in intervertebral disc degeneration based on bioinformatics analysis

作　　者：杜文佳[1] 晏丽 李延宏[1] Du Wenjia;Yan Li;Li Yanhong(Lanzhou University Second Hospital/Gansu Provincial Key Laboratory of Osteoarthriti,Lanzhou 730030,China;Lanzhou Modern Vocational and Technical College,Lanzhou 730000,China)

机构地区：[1]兰州大学第二医院/甘肃省骨关节病重点实验室,甘肃兰州730030 [2]兰州现代职业技术学院,甘肃兰州730000

出　　处：《甘肃医药》2022年第6期481-486,共6页Gansu Medical Journal

基　　金：甘肃省高等学校创新基金项目(编号:2021B-045)。

摘　　要：目的:通过使用生物信息学方法分析高通量芯片,揭示与椎间盘退变(IDD)相关的信号通路和miRNA-mRNA的调控关系。方法:首先,从GEO(Gene Expression Omnibus)数据库下载了IDD相关的两个数据集:GSE56081和GSE116726。使用R编程环境的limma软件包鉴定出IDD样本和正常样本的差异表达基因(DEGs)和差异表达miRNA(DE-miRNAs),并且对DEGs进行了GO(Gene Ontology)功能富集分析和KEGG(Kyoto Encyclopedia of Genes and Genomes)分析,以鉴定IDD中DEGs相关的生物学功能。通过miRTarBase数据库筛选出DE-miRNAs经过试验验证的靶基因,并将靶基因与DEGs取交集,最终构建高度可信的miRNA-mRNA调控关系网络,通过Cytoscape软件将其可视化。结果:总共筛选出523个DEGs和858个DE-miRNAs。GO分析表明,DEGs可能参与的生物过程(BP)包括生物调节、代谢过程、对刺激的反应、多细胞生物过程、细胞通讯、定位等;细胞成分(CC)主要涉及细胞膜、细胞核、含蛋白质复合物、细胞外基质、细胞投射、细胞骨架等;分子功能(MF)主要包括蛋白质结合、离子结合、核酸结合、转移酶活性、水解酶活性、结构分子活性等。KEGG途径分析表明,鉴定出的DEGs可能主要通过TGF-β信号通路、TNF信号通路、雌激素信号通路、PI3K-Akt信号通路四条通路影响IDD的进程。最后分析出32对miRNAs-mRNAs的调控关系。结论:本研究鉴定了可能参与IDD的信号通路和高度可信的miRNA-mRNA调控关系,为研究IDD的分子机制提供了新的理论依据和研究方向。Objective:We performed a bioinformatics analysis of the high-throughput chips in human to reveal the signaling pathways and miRNA-mRNA associated with the pathogenesis of intervertebral disc degeneration(IDD).Methods:Firstly,two IDD-related data sets,GSE56081 and GSE116726,were downloaded from the GEO(Gene Expression Omnibus)database.After that,differentially expressed genes(DEGs)and differentially expressed miRNAs(DE-miRNAs)were identified between IDD and normal samples using limma software packages in the R programming environment.In addition,GO(Gene Ontology)functional enrichment analysis and KEGG(Kyoto Encyclopedia of Genes and Genomes)analysis were performed to identify the biological functions of DEGs in IDD.After that,the target genes verified by experiments of DE-miRNAs were screened out through miRTarBase database,and the intersection of target genes and DEGs was obtained.Finally,a highly credible mirNA-mRNA regulatory network was constructed,and it was visualized by Cytoscape software.Results:In total,523 DEGs and 858 DE-miRNAs were identified.Go term showed DEGs are mainly related to biological process(BP):biological regulation,metabolic process,response to stimulus,multicellular organismal process,cell communication,localization;the main cellular components(CC):membrane,nucleus,protein-containing complex,endomembrane system,extracellular matrix,cell projection,cytoskeleton and so on;mediated molecular function(MF):protein binding,ion binding,nucleic acid binding,transferase activity,hydrolase activity,structural molecule activity.The KEGG pathway indicated it may play vital roles in the process of IDD that were TGF-βsignaling pathway,TNF signaling pathway,Estrogen signaling pathway and PI3K-Akt signaling pathway.Finally,a total of 32 miRNA-mRNAs were identified and constructed.Conclusion:This study identified the signaling pathways and miRNA-mRNA that may be involved in IDD,and provided a new theoretical basis and research direction for the molecular mechanism of IDD.

关 键 词：椎间盘退变 差异表达基因 生物信息学 miRNA-mRNA 

分 类 号：R681.53[医药卫生—骨科学]