基于生物信息学探索let-7c-5p通过靶向OLFM4参与支气管哮喘疾病进展研究

Exploring the involvement of let-7c-5p in the progression of bronchial asthmaby targeting OLFM based on bioinformatics

目的基于生物信息学探索let-7c-5p通过靶向OLFM4参与支气管哮喘疾病进展。方法选取基因表达公共数据库(GEO)中芯片数据集GSE207751和GEO222894,采用R软件的“Limma”和“DESeq2”软件包分析2个数据集中的差异表达基因(DEGs)和差异miRNA。利用hclust函数进行WCGNA分析。应用“ClusterProfiler”软件包进行基因本体(GO)功能注释富集分析和京都基因与基因组百科全书信号通路富集分析,STRING数据库建立蛋白互作网络(PPI网络),Cytoscape筛选严重哮喘患者的核心基因。miRWalk、miRBase和miRTarBase数据库用于靶基因的miRNA预测。结果分析获得80个DEGs,包括上调的OLFM4,进行WCGNA分析后发现和哮喘严重程度相关的Darked模块基因24个,之后进行PPI网格构建和mRNA-miRNA预测筛选出4个核心上调基因(包括OLFM4)和6个miRNA(包括hsa-let-7c-5p)。分析获得98个差异表达miRNA,其中上调5个,下调93个。进行轻度哮喘患者和重度哮喘患者差异miRNA交叉分析发现,let-7c-5p在轻度哮喘患者和重度哮喘患者中表达下调。结论研究多重验证了在哮喘患者中,let-7c-5p通过调控OLFM4影响哮喘的气道炎症和气道重塑,参与哮喘疾病进展,有利于了解哮喘疾病状态进展的潜在分子机制,同时验证了let-7c-5p成为哮喘潜在生物标志物的潜力,为进一步研究哮喘疾病进展提供理论基础。

Objective To explore the involvement of let-7c-5p in the progression of bronchial asthma by targeting OLFM based on bioinformatics.Methods The microarray data sets GSE207751 and GEO222894 in the Gene Expression Omnibus(GEO)database were selected.The“imma”and“DESeq2”software packages of R software were used to analyze the differentially expressed genes(DEGs)and differentially expressed miRNAs in the two data sets.WCGNA analysis was performed using the hclust function.The“ClusterProfiler”software package was used for gene ontology(GO)functional annotation enrichment analysis and Kyoto Encyclopedia of Genes and Genomes signal pathway enrichment analysis.The STRING database was used to establish a protein interaction network(PPI network),and Cytoscape was used to screen the core genes of patients with severe asthma.The miRWalk,miRBase and miRTarBase databases were used for miRNA prediction of target genes.Results A total of 80 DEGS were obtained,including up-regulated OLFM4.After WCGNA analysis,24 Darked module genes related to the severity of asthma were found.Four core up-regulated genes(including OLFM4)and six miRNAs(including hsa-let-7c-5p)were screened out by PPI grid construction and mRNA-miRNA prediction.A total of 98 differentially expressed miRNAs were obtained,of which five were up-regulated and 93 were down-regulated.Cross-analysis of differential miRNAs between mild asthma patients and severe asthma patients showed that let-7c-5p was down-regulated in mild asthma patients and severe asthma patients.Conclusion This study has repeatedly verified that let-7c-5p affects airway inflammation and airway remodeling of asthma by regulating OLFM4 in asthma patients,and participates in the progression of asthma disease,which is conducive to understanding the potential molecular mechanism of the progression of asthma disease.At the same time,it has verified the potential of let-7c-5p as a potential biomarker for asthma,which provides a theoretical basis for further study of the progression of asthma disease.