哮喘是一种由环境和宿主相互作用引起的慢性呼吸系统疾病。支气管上皮细胞（BECs）是对环境毒素的首要防线。然而，支持支气管上皮细胞在严重哮喘（SA）中的作用机制尚未完全了解。长链非编码RNA（lncRNA）和microRNA（miRNA）已被证明在SA发病机制中的基因表达调控中扮演重要角色。本研究首次采用生物信息学揭示了SA中BECs的lncRNA-miRNA-mRNA调控网络。从基因表达数据共享数据库(GEO)下载了SA患者和健康对照组的5个支气管刷取样本的mRNA数据集。采用Venn图和稳健等级聚合（RRA）方法的组合用于鉴定核心差异表达基因（DEGs）。对核心DEGs进行蛋白质-蛋白质相互作用（PPI）分析以筛选枢纽基因。miRDB、miRWalk和ENCORI数据库用于预测miRNA-mRNA关系，ENCORI和starBase v2.0数据库用于预测miRNA-mRNA关系的上游lncRNA。鉴定出四个核心DEGs：癌胚抗原相关细胞粘附分子5（CEACAM5）、白细胞介素-1受体类型2（IL1R2）、三叶红三维（TFF3）和血管内皮生长因子A（VEGFA）。这些四个核心DEGs表明SA与性别无显著相关性。富集分析显示MAPK、Rap1、Ras、PI3K-Akt和钙信号通路可能作为BECs在SA中的主要途径。构建了严重哮喘支气管上皮lncRNA-miRNA-mRNA调控网络。前10个竞争性内源性RNA（ceRNAs）为FGD5反义RNA 1（FGD5-AS1）、肺癌转移相关转录本1（MALAT1）、X染色体特异性转录本（XIST）、HLA复合物族群18（HCG18）、小核糖核酸宿主基因16（SNHG16）、hsa-miR-20b-5p、hsa-miR-106a-5p、hsa-miR-106b-5p、hsa-miR-519d-3p和Fms相关酪氨酸激酶1（FLT1）。本研究揭示了BECs在SA中的潜在lncRNA-miRNA-mRNA调控网络机制。© 2023 作者。由Wolters Kluwer Health, Inc出版。

Asthma is a chronic respiratory disease caused by environment-host interactions. Bronchial epithelial cells (BECs) are the first line of defense against environmental toxins. However, the mechanisms underlying the role of BECs in severe asthma (SA) are not yet fully understood. Long noncoding RNAs (lncRNAs) and microRNAs (miRNAs) have been shown to play important roles in the regulation of gene expression in the pathogenesis of SA. In this study, bioinformatics was used for the first time to reveal the lncRNA-miRNA-mRNA regulatory network of BECs in SA. Five mRNA datasets of bronchial brushing samples from patients with SA and healthy controls (HC) were downloaded from the Gene Expression Omnibus (GEO) database. A combination of the Venn diagram and robust rank aggregation (RRA) method was used to identify core differentially expressed genes (DEGs). Protein-protein interaction (PPI) analysis of core DEGs was performed to screen hub genes. The miRDB, miRWalk, and ENCORI databases were used to predict the miRNA-mRNA relationships, and the ENCORI and starBase v2.0 databases were used to predict the upstream lncRNAs of the miRNA-mRNA relationships. Four core DEGs were identified: carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5), interleukin-1 receptor type 2 (IL1R2), trefoil factor 3 (TFF3), and vascular endothelial growth factor A (VEGFA). These 4 core DEGs indicated that SA was not significantly associated with sex. Enrichment analysis showed that the MAPK, Rap1, Ras, PI3K-Akt and Calcium signaling pathways may serve as the principal pathways of BECs in SA. A lncRNA-miRNA-mRNA regulatory network of the severe asthmatic bronchial epithelium was constructed. The top 10 competing endogenous RNAs (ceRNAs) were FGD5 antisense RNA 1 (FGD5-AS1), metastasis associated lung adenocarcinoma transcript 1 (MALAT1), X inactive specific transcript (XIST), HLA complex group 18 (HCG18), small nucleolar RNA host gene 16 (SNHG16), has-miR-20b-5p, has-miR-106a-5p, hsa-miR-106b-5p, has-miR-519d-3p and Fms related receptor tyrosine kinase 1 (FLT1). Our study revealed a potential mechanism for the lncRNA-miRNA-mRNA regulatory network in BECs in SA.Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.