特发性肺间质纤维化中长链非编码RNA及转录因子的生物信息学挖掘  

Integrated analysis of a gene correlation network identifies critical regulation of fibrosis by lncRNAs and TFs in idiopathic pulmonary fibrosis

作　　者：王凡 李培 许芳[3] 李风森[1] WANG Fan;LI Pei;XU Fang;LI Fengsen(Hospital of Traditional Chinese Medicine Affiliated to Xinjiang Medical University,Urumqi,Xinjiang 830000,P.R.China;Kelamayi City Dushanzi People’s Hospital,Kelamayi,Xinjiang 833699,P.R.China;Xinjiang Medical University,Urumqi,Xinjiang 830000,P.R.China)

机构地区：[1]新疆医科大学附属中医医院,新疆乌鲁木齐833000 [2]克拉玛依市独山子人民医院,新疆克拉玛依833699 [3]新疆医科大学,新疆乌鲁木齐833000

出　　处：《中国呼吸与危重监护杂志》2020年第6期554-562,共9页Chinese Journal of Respiratory and Critical Care Medicine

基　　金：新疆维吾尔自治区自然科学基金(2019D01A06);新疆医科大学研究生创新创业启动基金(CXCY2018003)。

摘　　要：目的应用生物信息学分析的方法探讨特发性肺间质纤维化(IPF)中差异表达的长链非编码RNA(lncRNAs)及转录因子(TFs)。方法从NCBI基因表达芯片数据库(GEO)下载与IPF相关的三个基因表达谱(GSE2052、GSE44723以及GSE24206),根据NCBI Gene数据库及GENCODE v7数据库的基因注释信息,将下载的数据进行注释合并。然后应用R软件(3.6.0版本)的limma包,筛选出差异表达的基因(表达倍数>1或<–1,且P<0.05),并构建基因表达相关网络,采用R软件clusterProfiler包对差异表达的lncRNA及TFs进行功能富集分析,以推测其生物学功能。应用实时荧光定量聚合酶链反应验证筛选基因在IPF患者中的表达。结果筛选出8483个差异表达的基因,其中3个GEO数据集中共有29个共同差异表达的基因,采用功能及通路富集分析注释差异表达的基因,通过蛋白质–蛋白质互作网络获得18个模块,主要涉及多聚泛素、高尔基小囊泡转运、胞内吞等功能。采用超几何检验的方法获得IPF中差异表达的lncRNAs和TFs,并且相应的基因主要涉及泛素化介导的蛋白质水解、剪切体以及细胞周期等。其中的lncMALAT1、E2F1以及YBX1在IPF患者外周血中出现差异表达。结论lncMALAT1、E2F1以及YBX1可能是IPF发病和进展的调控基因,可为IPF的诊断治疗提供新途径。Objective To investigate the key long non-coding RNAs(lncRNAs)and transcription factors(TFs)in idiopathic pulmonary fibrosis(IPF)by Bioinformatics analysis.Methods Bioinformatics analysis of three gene expression profiles from the Gene Expression Omnibus dataset(GSE2052,GSE44723,and GSE24206),including 42 IPF and 21 normal lung tissues,was performed in this study.Subsequently,differentially expressed genes(DEGs)were filtered,and key genes involved in signaling pathways and the DEG-associated protein-protein interaction network(PPI)were further analyzed.The filtered genes expression was determined by real-time quantitative polymerase chain reaction analysis.Results A total of 8483 aberrantly expressed genes were screened,and 29 overlapping genes were identified among these three datasets.A significant enrichment analysis of DEG-associated functions and pathways was further performed.A total of 18 modules were obtained from the DEG PPI network,and most of the modules were involved in polyubiquitination,Golgi vesicle transport,endocytosis and so on.The key genes were obtained through hypergeometric testing,and most of the corresponding genes were closely associated with ubiquitin-mediated proteolysis,the spliceosome,and the cell cycle.These differential expressed genes,such as lncMALAT1,E2F1 and YBX1,were detected in the peripheral blood of IPF patients when compared with those normal control subjects.Conclusion lncMALAT1,E2F1 and YBX1 might be possible regulators for the pathogenesis of idiopathic pulmonary fibrosis.

关 键 词：特发性肺间质纤维化 长链非编码RNA 转录因子 基因表达 

分 类 号：R563[医药卫生—呼吸系统] Q811.4[医药卫生—内科学]