摘要
目的基于生物信息学筛选并鉴定骨关节炎与糖尿病的共同疾病基因及其相关微小RNA(miRNA)。方法在GEO数据库筛选骨关节炎和糖尿病相关基因芯片数据集GSE55235、GSE29221,通过GEO2R在线分析系统筛选出两者的差异表达基因后,使用R软件包“VennDiagram”取交集而获得共同疾病基因。利用DAVID数据库对共同疾病基因进行基因本体论分析及京都基因与基因组百科全书富集分析。通过STRING数据库构建共同疾病基因的蛋白质-蛋白质相互作用网络,再应用Cytoscape软件的4种计算方法分别对网络进行分析并筛选出得分最高的前10位基因,取交集后获得Hub基因。使用miRNet数据库预测Hub基因相关miRNA。结果共筛选出148个共同疾病基因,主要富集在肿瘤坏死因子、细胞外基质、成纤维细胞生长因子等相关生物功能,以及磷脂酰肌醇-3-激酶/蛋白激酶B、丝裂原活化蛋白激酶等信号通路中。最终获得CD44、胰岛素样生长因子1(IGF1)、C-C基序趋化因子配体5(CCL5)及Ⅰ型胶原α2链共4个Hub基因,及其对应5个miRNA(miRNA-26a-5p、miRNA-27a-3p、miRNA-98-5p、miRNA-34a-5p、miRNA-29c-3p)。结论CD44、IGF1、CCL5及其对应的miRNA-26a-5p、miRNA-27a-3p、miRNA-98-5p、miRNA-34a-5p同时在骨关节炎及糖尿病中发挥重要的调控作用,提示骨关节炎与糖尿病之间存在潜在联系。
Objective To screen and identify the common pathogenic genes and related microRNAs(miRNAs)of osteoarthritis and diabetes mellitus based on bioinformatics.Methods The osteoarthritis-and diabetes mellitus-related gene chip datasets,GSE55235 and GSE29221,were screened in GEO database,and their differently expressed genes(DEGs)were identified by GEO2R online analysis system,then the intersection of the DEGs was conducted by R software package VennDiagram to obtain the common pathogenic genes.DAVID database was employed to perform Gene Ontology functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis on the common pathogenic genes.The protein-protein interaction network of the common pathogenic genes had been established by STRING database,then the four computational methods of Cytoscape software were separately used to perform an analysis on the network,and the top 10 genes with the highest scores were screened out to obtain Hub genes after the intersection.The miRNAs associated with Hub genes were predicted by miRNet database.Results A total of 148 common pathogenic genes were selected,which were mainly enriched in the related biological functions such as tumor necrosis factor,extracellular matrix and fibroblast growth factor,and in signaling pathways including phosphoinositide-3-kinase/protein kinase B and mitogen-activated protein kinase.Ultimately,a total of four hub genes,CD44,insulin-like growth factor 1(IGF1),C-C motif chemokine ligand 5(CCL5)and collagen typeⅠalpha 2 chain,and five corresponding miRNAs(miRNA-26a-5p,miRNA-27a-3p,miRNA-98-5p,miRNA-34a-5p,miRNA-29c-3p)were obtained.Conclusion CD44,IGF1,and CCL5 and their corresponding miRNA-26a-5p,miRNA-27a-3p,miRNA-98-5p,miRNA-34a-5p simultaneously play an important role in the control and regulation of osteoarthritis and diabetes mellitus,which indicates a potential link between osteoarthritis and diabetes mellitus.
作者
袁长深
官岩兵
容伟明
李哲
梅其杰
延伟伟
段戡
YUAN Chang-shen;GUAN Yan-bing;RONG Wei-ming;LI Zhe;MEI Qi-jie;YAN Wei-wei;DUAN Kan(The Third Department of Orthopedics,the First Affiliated Hospital of Guangxi University of Chinese Medicine,Nanning 530023,China;Graduate School,Guangxi University of Chinese Medicine,Nanning 530000,China)
出处
《广西医学》
CAS
2022年第1期46-50,57,共6页
Guangxi Medical Journal
基金
国家自然科学基金(82060875)
广西中医药大学广西一流学科建设开放课题(2019XK030)
广西中医药大学自然科学研究项目(2019QN022)。
关键词
骨关节炎
糖尿病
生物信息学
差异表达基因
微小RNA
Osteoarthritis
Diabetes mellitus
Bioinformatics
Differentially expressed gene
MicroRNA
