小鼠耳蜗性聋的关键通路和差异表达基因分析  

Identification of Key Pathways and Genes in Mice of Cochlear Deafness using Bioinformatics Analysis

作　　者：杨媛媛[1] 黄冠江 陶源[1] Yang Yuanyuan;Huang Guanjiang;Tao Yuan(Department of Otorhinolaryngology,Peking University Shenzhen Hospital,Shenzhen,518000,China)

机构地区：[1]北京大学深圳医院耳鼻咽喉科,深圳518000 [2]浙江大学医学院附属第二医院耳鼻咽喉科

出　　处：《听力学及言语疾病杂志》2019年第4期398-405,共8页Journal of Audiology and Speech Pathology

基　　金：深圳市卫生计生系统科研项目(SZXJ2018079);深圳市医疗卫生三名工程项目(SZSM201612076)

摘　　要：目的 利用基因表达数据库查找6月龄的听力正常CBA小鼠和耳蜗性聋小鼠的表达谱基因芯片的原始数据,对关键通路和差异表达基因(differentially expressed genes,DEGs)进行数据库挖掘和分析,为耳蜗性聋的治疗提供参考。方法 从公共数据库基因表达数据库(gene expression omnibus,GEO)中下载小鼠耳蜗性聋表达谱相关数据集,采用R软件筛选差异表达基因并进行火山图分析,再将DEGs进行热图分析,采用David在线工具对其进行基因本体分析(gene ontology analysis,GO)、京都基因和基因组百科全书分析(kyoto encyclopedia of genes and genomes, KEGG),然后,将差异表达基因导入STRING在线数据库进行蛋白质互作网络分析(protein protein interaction network,PPI network),绘制差异表达基因互作网络图,并将互作网络数据导入Cytoscape软件中,筛选网络中心节点和关键基因,分析关键子网络。并对DEGs行基因集富集分析(gene set enrichment analysis,GSEA),筛选重要通路。结果 共筛选出191个DEGs,其中表达上调的基因79个,表达下调的基因112个。在GO分析中,上调的DEGs主要参与细胞外空间、细胞外区及趋化因子受体结合等过程,下调的DEGs主要参与有丝分裂核分裂、细胞周期及细胞分裂等过程。在KEGG分析中,上调的DEGs主要参与肿瘤坏死因子信号通路,下调的DEGs主要参与细胞周期、孕酮介导的卵母细胞成熟、卵母细胞的减数分裂及p53信号通路等。PPI网络筛选出前10个关键基因:Kif11、Cdc20、Cdk1、Bub1b、Ccnb2、Cdca8、Cdca5、Sgol1、Hmmr及Ncapg。GSEA分析显示:前三位上调的通路包括树突细胞成熟、Croonquist Nras信号转导及反应金属离子硫蛋白转运,而前三位下调的通路包括半乳糖代谢、氧化磷酸化及嘌呤代谢。结论 本研究得到了一个较全面的小鼠耳蜗性聋差异表达基因的生物信息学分析结果,但仍需进一步用基础实验来验证。Objective To identify gene signatures during cochlear deafness associated with the CBA mice samples (6 months old) and normal CBA mice samples (6 months old),and study the potential mechanisms.Methods The dataset of mouse cochlear deafness expression profiles was downloaded from GEO database.The differentially expressed genes (DEGs) were screened by R software.The DEGs were analyzed by the volcano map and heat map.The GO analysis and KEGG analysis were performed by using David online tool.Then,the DEGs were introduced into the STRING online database for analysis,and the differential gene interaction network map was drawn.The interaction network data was imported into Cytoscape software,which can select hub genes.The key sub-network was analyzed.Furthermore,GSEA was used to select important pathways.Results A total of 191 DEGs were screened,of which 79 genes were up-regulated genes and 112 genes were down-regulated genes.The GO analysis showed that up-regulated DEGs were enriched in biological processes (BP) significantly,including positive regulation of protein oligomerization,innate immune response and cell chemotaxis.The KEGG pathway analysis showed that up-regulated DEGs were enriched in TNF signaling pathway.The top 10 hub genes contained Kif11,Cdc20,Cdk1,Bub1b,Ccnb2,Cdca8,Cdca5,Sgol1,Hmmr and Ncapg,which were identified from PPI network.The sub-networks revealed that the related genes were involved in these significant pathways,including cell cycle,progesterone-mediated oocyte maturation,oocyte meiosis,p53 signaling pathway and viral carcinogenesis.Conclusion The results provide a comprehensive bioinformatics analysis of DEGs in mice with cochlear deafness,but more fundamental research is needed to validate the findings.Not only can the conclusion provide a new idea for the research direction of cochlear deafness,but also make a suggestive effect on the pathogenesis of cochlear deafness and the research of molecular targeted therapy.

关 键 词：小鼠 耳蜗性聋 通路 基因 

分 类 号：R764.43[医药卫生—耳鼻咽喉科]