变应性鼻炎中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 programmed cell death-related genes in allergic rhinitis

作　　者：王宇婷[1] 姜辉[1] 王嘉玺[1] WANG Yuting;JIANG Hui;WANG Jiaxi(Department of Otolaryngology,Dongfang Hospital of Beijing University of Traditional Chinese Medicine,Beijing 100078,China)

机构地区：[1]北京中医药大学东方医院耳鼻咽喉科,北京100078

出　　处：《中国耳鼻咽喉颅底外科杂志》2023年第3期54-63,共10页Chinese Journal of Otorhinolaryngology-skull Base Surgery

基　　金：2021年度北京中医药大学附属医院校级课题(2021-BUCMXJKY010)。

摘　　要：目的 本研究旨在探讨lncRNA介导的ceRNA网络在变应性鼻炎(AR)病理生理过程中的作用及其在程序性细胞死亡(PCD)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。采用基因本体(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PCD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进行靶器官定位网络分析。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。并对AC008394.1及人类组织相容性白细胞抗原复合物P5(HCP5)2个lncRNA构建PCD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。Objective To investigate the role of lncRNA-mediated ceRNA network in pathophysiology of allergic rhinitis(AR)and its potential regulatory functions in programmed cell death(PCD).Methods AR patients and normal subjects were included.Their whole blood samples were obtained 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 PCD 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,a PCD related ceRNA regulatory network for two lncRNAs,AC008394.1 and HCP5,was constructed.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 A new ceRNA network in AR is successfully constructed and preliminarily exploration reveals that HCP5-mediated ceRNA network may play a role in AR by affecting apoptosis,which provides new insights and potential research options for the study of AR pathogenesis.

关 键 词：变应性鼻炎 lncRNA ceRNA网络 程序性细胞死亡 人类组织相容性白细胞抗原复合物P5 

分 类 号：R765.21[医药卫生—耳鼻咽喉科]