摘要
目的miRNA在骨质疏松症的发生发展过程中发挥重要作用。文中旨在筛选与骨质疏松症密切相关的miRNA和基因,完成骨质疏松症miRNA-mRNA调控网络的构建。方法通过GEO数据库查找骨质疏松症的基因芯片表达谱,采用GEO2R进行分析并筛选差异表达基因(DEGs)和差异表达miRNA,采用火山图对差异基因和miRNA进行展示,然后通过David在线数据库完成GO和KEGG通路分析,String在线数据库用于完成PPI蛋白网络分析。采用TargetScan、miRTarBase和miRDB预测靶基因,最后通过Cytoscape软件进行PPI和miRNA-mRNA调控网络可视化。结果通过筛选得到15个差异miRNA和174个差异表达基因。通过GO和KEGG通路分析得到25条GO功能注释,生物过程包括对药物的反应、血管生成、离子迁移、GTPase介导的信号转导的调控、适应性免疫反应等,KEGG富集分析得到NF-κB信号通路、HIF-1信号通路和谷胱甘肽代谢。通过cytohubba插件得到10个hub基因,分别为:CDH2、POLR2A、KLF4、CCND1、SOX4、NCBP2、VEGFA、PKLR、EP300、HNRNPL。7个miRNA(2个上调的miRNA,5个下调miRNA)分别为:hsa-miR-18b-5p,hsa-miR-194-5p上调,hsa-miR-4768-3p,hsa-miR-4269,hsa-miR-4717-3p,hsa-miR-629-3p,hsa-miR-4793-3p下调。对7个miRNA进行预测得到3065个靶基因,然后与174个DEGs交集得到44个交集基因,最后成功构建miRNA-mRNA网络调控图。hsa-miR-4269和hsa-miR-194-5p与其调控的靶基因表达呈现正相关关系比较多。结论miR-194-5p在骨质疏松症中显著上调,可能通过调控其靶基因CDH2在骨质疏松症中发挥重要作用,为骨质疏松症的诊断和治疗提供了候选靶点。
Objective MicroRNAs(miRNA)play an important role in the development and regression of osteoporosis.This study aims to screen for miRNAs and genes closely related to osteoporosis,and to complete the construction of a miRNA-mRNA regulatory network of osteoporosis.Methods The gene chip expression profile of osteoporosis was obtained through the GEO database,and the differentially expressed genes(DEGs)and miRNAs were analyzed and screened via GEO2R.We used volcanic maps to display differential genes and miRNAs,and completed the GO and KEGG pathway analysis through the David online database.The String online database is used to complete PPI protein network analysis.The TargetScan,miRTarBase and miRDB were used to predict the targeted genes.Finally,the PPI and miRNA-mRNA regulatory networks were visualized by Cytoscape software.Results We obtained 15 differential miRNAs and 174 differentially expressed genes through screening.The GO enrichment analysis mainly focused on drug response,angiogenesis,ion transport,regulation of small GTPase mediated signal ransduction,adaptive immune response,etc.NF-κB signaling pathway and HIF-1 signal were obtained through KEGG enrichment analysis.We obtained 10 hub genes through the cytohubba plug-in.We also obtained 3065 targeted genes by processing of seven miRNAs,and then intersected them with 174 DEGs to obtain 44 intersection genes.Finally,we successfully constructed a regulation map of miRNA-mRNA network.The miR-194-5p is significantly up-regulated in osteoporosis.Conclusion The miR-194-5p might play an important role in osteoporosis by regulating its target gene CDH2,which provides candidate targets for the diagnosis and treatment of osteoporosis.
作者
汪悦东
万雷
张志海
黄宏兴
朱根福
WANG Yue-dong;WAN Lei;ZHANG Zhi-hai;HUANG Hong-xing;ZHU Gen-fu(The Third Clinical Medical College of Guangzhou University of Chinese Medicine,Guangzhou 510405,Guangdong,China;Department of Orthopedics,The Third Affiliated Hospital of Guangzhou University of Chinese Medicine,Guangzhou 510000,Guangdong,China)
出处
《医学研究生学报》
CAS
北大核心
2020年第3期258-263,共6页
Journal of Medical Postgraduates
基金
广东省中医药局科研项目(20193008)
广州市海珠区科技计划项目(海科工商信计2018-94、2018-96)。
