Exosomal LncRNA and CircRNA Regulate Peripheral Blood Mononuclear Cell Function through a Competitive Endogenous RNA Mechanism in Allergic Rhinitis.

IF 2.5 4区 医学 Q3 ALLERGY International Archives of Allergy and Immunology Pub Date : 2024-11-21 DOI:10.1159/000542695
Guangyao Mao, Qian Zhu, Yiyun Zeng, LiQiang Cong, Jun Ye, Xuhui Kong
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Abstract

Introduction: Peripheral blood mononuclear cells (PBMCs) dysfunction is involved in the pathogenesis and progression of allergic rhinitis (AR). This study aims to investigate the competing endogenous RNA (ceRNA) networks in PBMCs influenced by differentially expressed long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs) found in plasma exosomes induced by AR.

Methods: All subjects were from the Affiliated Taizhou People's Hospital of Nanjing Medical University. Differential expression of messenger RNA (mRNAs) in PBMCs and lncRNAs/circRNAs in plasma exosomes was analyzed using high-throughput sequencing. Differentially expressed lncRNAs and circRNAs that target mRNAs were identified using bioinformatics methods. The predicted target mRNAs were intersected with the differentially expressed mRNAs in PBMCs to construct ceRNA networks. The subcellular localizations of lncRNAs and circRNAs within the ceRNA networks were determined using RNA fluorescence in situ hybridization or bioinformatics methods. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses of differentially expressed mRNAs in PBMCs were conducted using the clusterProfiler R package. Quantitative reverse transcription polymerase chain reaction was used to validate the expression levels of each molecule within the constructed ceRNA networks in clinical samples, along with receiver operating characteristic (ROC) curve analysis to assess diagnostic value. Further validation was performed using in vitro cultured PBMCs and dual-luciferase reporter assays.

Results: Five differentially expressed circRNAs and 31 differentially expressed lncRNAs were identified in exosomes. In PBMCs, 130 differentially expressed mRNAs were identified. Six ceRNA networks were constructed, affecting PBMCs chemorepellent activity, JAK-STAT signaling pathway, and other functions or pathways. The expression level of ENST00000650850 in plasma exosomes was significantly lower in AR patients, suggesting its potential diagnostic value. The expression level of ENST00000650850 in plasma exosomes was positively correlated with the expression levels of ENST00000650850 and IL6 mRNA in PBMCs. PBMCs from healthy individuals were stimulated with plasma exosomes isolated from AR patients, leading to a reduction in IL6R mRNA expression levels in the PBMCs.

Conclusion: Differentially expressed lncRNA (ENST00000650850) in plasma-derived exosomes of AR patients may regulate IL6R mRNA expression in PBMCs via miR-6747-3p, thereby influencing PBMC function and contributing to the pathogenesis and progression of AR.

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过敏性鼻炎患者外泌体 LncRNA 和 CircRNA 通过竞争性内源性 RNA 机制调控外周血单核细胞功能
简介外周血单核细胞(PBMCs)功能障碍与过敏性鼻炎(AR)的发病机制和进展有关。本研究旨在探讨AR诱导的血浆外泌体中差异表达的长非编码RNA(lncRNA)和环状RNA(circRNA)对PBMCs竞争性内源性RNA(ceRNA)网络的影响:所有受试者均来自南京医科大学附属泰州人民医院。方法:所有受试者均来自南京医科大学附属泰州人民医院,采用高通量测序技术分析了PBMCs中mRNAs和血浆外泌体中lncRNAs/circRNAs的差异表达。利用生物信息学方法鉴定了靶向mRNA的差异表达lncRNA和circRNA。将预测的靶mRNA与PBMCs中差异表达的mRNA交叉,构建了ceRNA网络。利用 RNA 荧光原位杂交或生物信息学方法确定了 lncRNA 和 circRNA 在 ceRNA 网络中的亚细胞定位。使用clusterProfiler R软件包对PBMC中差异表达的mRNA进行了基因本体(GO)和京都基因组百科全书(KEGG)分析。采用定量反转录聚合酶链反应(qRT-PCR)验证构建的 ceRNA 网络中每个分子在临床样本中的表达水平,并通过接收者操作特征曲线(ROC)分析评估诊断价值。使用体外培养的 PBMC 和双荧光素酶报告基因检测法进行了进一步验证:结果:在外泌体中发现了5个差异表达的circRNA和31个差异表达的lncRNA。在 PBMCs 中,确定了 130 个差异表达的 mRNA。构建的6个ceRNA网络影响了PBMCs的驱虫活性、JAK-STAT信号通路以及其他功能或通路。血浆外泌体中ENST00000650850的表达水平在AR患者中明显降低,这表明它具有潜在的诊断价值。血浆外泌体中ENST00000650850的表达水平与PBMCs中ENST00000650850和IL6 mRNA的表达水平呈正相关。用从AR患者体内分离出的血浆外泌体刺激健康人的PBMCs,会导致PBMCs中IL6R mRNA表达水平的降低:结论:AR患者血浆外泌体中差异表达的lncRNA(ENST00000650850)可能通过miR-6747-3p调控PBMCs中IL6R mRNA的表达,从而影响PBMC的功能并导致AR的发病和进展。
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来源期刊
CiteScore
5.60
自引率
3.60%
发文量
105
审稿时长
2 months
期刊介绍: ''International Archives of Allergy and Immunology'' provides a forum for basic and clinical research in modern molecular and cellular allergology and immunology. Appearing monthly, the journal publishes original work in the fields of allergy, immunopathology, immunogenetics, immunopharmacology, immunoendocrinology, tumor immunology, mucosal immunity, transplantation and immunology of infectious and connective tissue diseases.
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