过敏性鼻炎中lncRNA-miRNA-mRNA网络构建与相关程序性细胞死亡基因的分析

Construction of lncRNA-miRNA-mRNA network and analysis of related programmed cell death genes in allergic rhinitis

摘要:

目的：本研究旨在探讨lncRNA介导的ceRNA网络在变应性鼻炎（allergic rhinitis, AR）病理生理过程中的作用及其在程序性细胞死亡中的潜在调控功能。方法：纳入AR患者与正常人，取全血进行RNA测序分析，筛选差异表达的lncRNA、miRNA和mRNA用于构建基于ceRNA理论的lncRNA-miRNA-mRNA调控网络。采用GO和KEGG富集分析来预测ceRNA网络中mRNA的潜在生物学功能。随后，将差异表达的mRNA与程序性细胞死亡相关基因相互取交集，并依据交集mRNA构建新的ceRNA网络，同时对ceRNA网络中mRNA进行靶器官定位网路分析。结果：基于生物信息学分析，共提取5个lncRNA、4个miRNA和46个mRNA，构建AR中lncRNA介导的上调及下调的ceRNA网络。功能富集分析显示其在“钙信号通路”、“PI3K/AKT信号通路”及“ERK1和ERK2级联”等中显著富集。接下来我们对AC008394.1及HCP5两个lncRNA构建程序性细胞死亡相关ceRNA调控网络。在对ceRNA网络中mRNA进行靶器官定位分析中发现，它们多在神经免疫相关器官中表达。结论：本研究构建了AR中新的ceRNA网络，初步探索了HCP5介导的ceRNA网络可能通过影响细胞凋亡对AR发挥作用。为AR发病机制的研究提供了新的见解和潜在的研究方案。

Abstract:

Objective:This study aimed to investigate the role of lncRNA-mediated ceRNA network in AR pathophysiology and its potential regulatory functions in programmed cell death. Methods: Allergic rhinitis patients and normal subjects were included, whole blood was taken for RNA sequencing analysis, and differentially expressed lncRNA, miRNA and mRNA were screened to construct a lncRNA-miRNA-mRNA regulatory network based on ceRNA theory. GO and KEGG enrichment analyses were employed to predict the potential biological functions of mRNAs in the ceRNA network. Subsequently, the differentially expressed mRNAs interacted with programmed cell death-related genes, and a new ceRNA network was constructed, and target organ localization network analysis was performed on mRNAs in the network. Results: Based on bioinformatics analysis, a total of 5 lncRNAs, 4 miRNAs and 46 mRNAs were extracted, and the ceRNA network of lncRNA-mediated up-regulation and down-regulation in AR was constructed. Functional enrichment analysis showed that it was significantly enriched in "calcium signaling pathway", "PI3K/AKT signaling pathway" and "ERK1 and ERK2 cascade". Next, we constructed a programmed cell death-related ceRNA regulatory network for two lncRNAs, AC008394.1 and HCP5. In the target organ localization analysis of mRNAs in the ceRNA network, it was found that they were mostly expressed in neuroimmune-related organs. Conclusion: This study constructs a new ceRNA network in AR, and preliminarily explores that HCP5-mediated ceRNA network may play a role in AR by affecting apoptosis. It provides new insights and potential research options for the study of AR pathogenesis.