利用生物信息学探究IL4在哮喘中的异常表达及其相关基因的功能作用

Analysis of the abnormal expression of IL4 in asthma and the function of related genes by bioinformatics

目的研究IL4在哮喘中的表达情况,探讨其异常表达的原因及其相关基因对哮喘可能的作用机制。方法从基因表达综合数据库(Gene Expression Omnibus,GEO)下载哮喘患者与正常对照样本的mRNA、miRNA、lncRNA的表达数据及甲基化数据。独立样本秩和检验比较哮喘患者与正常对照样本的IL4的表达差异和甲基化差异。通过预测IL4互作的miRNA及miRNA互作的lncRNA,建立了调控IL4的ceRNA网络。基因富集分析探究了IL4高表达哮喘患者富集的通路。最后Pearson相关性分析挖掘出与IL4表达相关性显著的基因,并对这些基因的功能及所在的通路进行了富集分析。结果哮喘患者与正常对照样本相比,IL4表达水平显著上调,甲基化水平显著下调(P<0.05),说明甲基化修饰可能是导致IL4异常表达原因之一。通过构建ceRNA网络发现,IL4的异常表达也可能是受到6个lncRNA的调控作用。这些lncRNA通过吸附在调控IL4的miRNA上,抑制了miRNA对IL4的下调作用,导致IL4在哮喘中上调。基因富集分析显示IL4高表达患者中富集的多为代谢相关通路。与IL4表达显著相关的基因,显著富集于与哮喘发生相关的通路,如花生四烯酸代谢通路、内吞作用和幽门螺杆菌感染中的上皮细胞信号转导通路等。结论 IL4可能可以作为治疗哮喘的新的靶点,IL4及其相关基因通过调控哮喘发生相关的通路,促使哮喘发生。

Objective To investigate the abnormal expression of IL4 in asthma and the function of related genes.Methods The mRNA,miRNA,lncRNA expression data and methylation data of asthma patients and normal control samples were downloaded from Gene Expression Omnibus(GEO).The expression level and methylation level of IL4 were compared between asthmatic patients and normal controls by Mann-Whitney U test.By predicting the interaction between IL4 and miRNA,and the interaction between IncRNA and miRNA,the ceRNA network regulating IL4 was established.Gene set enrichment analysis explored the pathway of IL4 overexpression in asthmatic patients.Genes significantly related to IL4 expression were screened by pearson algorithm and performed with functional enrichment analysis.Results Compared with the control group,the expression level of IL4 was significantly upregulated and the methylation level was significantly downregulated in asthmatic patients(P<0.05),suggesting that methylation may be one of the reasons for the abnormal expression of IL4.Through the construction of ceRNA network,it was found that the abnormal expression of IL4 may be regulated by six lncRNAs.These lncRNAs inhibited the downregulation of IL4 by adsorbing on miRNAs that regulate IL4,leading to the upregulation of IL4 in asthma.Gene set enrichment analysis showed that most of the IL4 overexpression asthmatic patients were enriched in metabolic pathways.The genes significantly related to IL4 expression were enriched in the pathways related to the development of asthma,such as the arachidonic acid metabolism,endocytosis and epithelial cell signaling in Helicobacter pylori infection.Conclusion IL4 may be a new target for the treatment of asthma.IL4 and its related genes in asthma may promote the occurrence of asthma by regulating related pathways.