摘要
目的通过生物信息学方法分析骨关节炎(OA)患者与正常人血清微小RNAs(miRNAs)表达差异。方法从基因表达数据库(GEO)和ArrayExpress数据库中查找OA血清相关的芯片数据,并下载GSE105027数据集。筛选样本包括8例OA患者血清和12例正常(NC)人样本,其中女性患者5例,健康女性7例。用R语言Limma包分别筛选出男/女性OA和男/女性NC之间的差异表达miRNAs(DEMs),设定阈值为P<0.05和Ilog2FCI>1,用ggplot2包绘制火山图和韦恩图,得到2个DEMs:hsa-miR-33b-3p和hsa-miR-4284。用STRING和Cytoscape软件构件蛋白互作网络图(PPI)网络,依据LncBase和MNDR数据库筛选相关的长链非编码RNA(lncRNAs),绘制内源竞争RNA(ceRNA)网络互作图,Cytohubba筛选出关键基因,结合NONCODE和lncRNASNP2数据库筛选与骨关节炎相关的lncRNAs,得出关键调控轴。结果共筛选出男、女性共有的DEMs2个:hsa-miR-33b-3p和hsa-miR-4284,均为下调。结合ceRNA网络及数据库综合分析出lncRNA KCNQ1OT1-miR-33b-3p-PIK3CA轴。结论通过生物信息学分析结果显示OA和NC的血清miRNAs表达差异集中在细胞凋亡、炎症和代谢,而lncRNAKCNQ1OT1-miR-33b-3p-PIK3CA轴在OA发病机制中尤为很重要。
Objective To analyze the differences in the expression of serum microRNAs(miRNAs)between osteoarthritis(OA)patients and normal people through bioinformatics methods.Methods We searched OA serum-related chip data from Gene Expression Omnibus(GEO)and ArrayEx-press databases,and downloaded the GSE105027 data set.The screening samples included 8 OA patients'serum and 12 normal(NC)human samples,including 5 female patients and 7 healthy women.We used the R language limma package to screen the differentially expressed miRNAs(DEMs)between male/female OA and male/female NC,set the threshold to P<0.05&Ilog2FCI>1,and used the ggplot2 package to draw volcano maps and venn diagrams to obtain 2 DEMs:hsa-miR-33b-3p and hsa-miR-4284.Using STRING and Cytoscape software,to construct protein-protein interaction(PPI)network,we screened relat-ed long-stranded non-coding RNA(lncRNAs)based on LncBase and MNDR database,to draw competing endogenous RNAs(ceRNA)network interaction mapping,screened out key genes by the cytohubba,to screen out LncRNAs related to osteoarthritis with NONCODE and IncRNASNP2 database,and get the key regulation axis.Results A total of 2 DEMs shared by males and females were screened:hsa-miR-33b-3p and hsa-miR-4284,both of which were down-regulated.We comprehensively analyzed the database with the ceRNA network and found the LncRNA KCNQ1OT1-miR-33b-3p-PIK3CA axis.Conclusion Through bioin-formatics analysis,it is found that the differences in serum miRNAs expression between OA and NC are concentrated in apoptosis,inflammation and metabolism,and the LncRNA KCNQ1OT1-miR-33b-3p-PIK3CA axis is particularly important in the pathogenesis of OA.
作者
许炎
杨威
邢欢欢
裴洪
Xu Yan;Yang Wei;Xing Huanhuan;Pei Hong(Department of Orthopedics,the Affiliated Jingzhou Hospital of Yangtze University,Jingzhou 434000,China;Department of Orthopedics,the Affiliated People's Hospital of Hubei University of Medicine,Shiyan 442000,China;Hubei University of Medicine,Shiyan 442000,China)
出处
《中华实验外科杂志》
CAS
北大核心
2023年第7期1285-1289,共5页
Chinese Journal of Experimental Surgery
基金
长江大学医学科研联合发展基金项目(WJ2019-33)。