microRNA对儿童哮喘靶基因调控的生物信息学分析

Bioinformatic analysis of regulation of microRNA on target genes in pediatric asthma

目的应用生物信息学技术分析尘螨过敏哮喘儿童特异性microRNA(miRNA)及其靶基因筛选,探讨哮喘发病机制。方法采用病例对照研究,在62对尘螨过敏哮喘患儿及同龄正常无过敏儿童中,随机选取12例哮喘患儿及对照者进行microRNA芯片分析,比较两组中存在异常表达的miRNAs,并在其余病例中进行RT-qPCR验证和生物信息学分析。结果尘螨过敏哮喘儿童中有6个microRNA表达较对照组下调2倍以上,分别为miRNA-151a-5p、625-5p、126-3p、513a-5p、27b-3p、22-3p,差异均有统计学意义(P<0.05)。进一步的生物信息学富集分析发现,这些microRNAs调控的PPARGC1B、CBL、ONECUT2、ESR1、EGFR、SYK、STAT1与炎症因子信号通路有着显著性关联(P<0.05)。结论 miRNA-625-5p、513a-5p、27b-3p、22-3p可能通过共同调控相关靶基因,形成一个网络通路,参与尘螨诱发儿童哮喘的发生。

Objective To understand the underlying mechanism of mites-induced pediatric asthma by bioinformatic analysis on specific microRNA（miRNA） array and target gene screening.Methods This is a case control study of 62 pairs of dust mites-induced asthma children with age and gender matched healthy controls.Twelve pairs were randomly selected for miRNA array.The abnormal expression of miRNAs was compared between asthma and control children.The results were validated by RT-q PCR and bioinformatic analysis in remaining pairs of children.Results Six miRNAs（miRNA-151a-5p,625-5p,126-3p,513a-5p,27b-3p,22-3p） were significantly down-regulated more than two folds in dust mites-induced asthma children than those in controls.The enriched bioinformatics analysis showed that these miRNAs and their target genes CBL,PPARGC1 B,ESR1,ONECUT2,EGFR,SYK,and STAT1 were related to inflammatory cytokine signaling pathway.ConclusionIt is suggested that mi R-22-3p,513a-5p,625-5p,27b-3p,and miRNA-target genes form a network through co-regulation to target genes to participate dust mites-induced asthma in children.