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基于lncRNA-mRNA共表达网络分析探索CXCL16分子相关抗原呈递的调控机制

Exploring the Regulatory Mechanism of CXCL16 Molecule-Related Antigen Presentation Using lncRNA-mRNA Co-Expression Network Analysis.

作者信息

Liu Ting-Ting, Zheng Shuai, Jia Li-Xin, Du Jie, Piao Chunmei

机构信息

Beijing Institute of Heart, Lung and Blood Vessel Diseases, The Key Laboratory of Remodeling Cardiovascular Diseases, Ministry of Education, Collaborative Innovation Center for Cardiovascular Disorders, Beijing Anzhen Hospital, Capital Medical University, Beijing, People's Republic of China.

出版信息

J Inflamm Res. 2024 Dec 24;17:11561-11575. doi: 10.2147/JIR.S496133. eCollection 2024.

Abstract

AIM

To investigate the regulatory mechanism of CXCL16 molecule-related ( extract-induced antigen presentation in a mouse asthma model based on the long non-coding RNA (lncRNA) and mRNA expression profile.

METHODS

knockout mice and wild-type mice were administered with . extract by intratracheal instillations to induce asthma airway inflammation. High throughput chip sequencing was used to screen for lncRNA and mRNA expression profile differences in lung tissue between the groups. A lncRNA-mRNA co-expression network was constructed through gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Wild-type mice received intraperitoneal injections with CXCL16 neutralizing antibodies, and the bioinformatics and inflammation results were validated using RT-PCR and ELISA.

RESULTS

Compared with wild-type mice, CXCL16 knockout mice showed 120 lncRNA and 388 mRNA upregulated in lung tissue, while 1984 lncRNA and 301 mRNA were downregulated. The constructed lncRNA-mRNA co-expression network included 244 differentially expressed lncRNAs and 49 differentially expressed mRNAs. Among them, the core network's expression of the hub gene Idh1 and the top four lncRNAs was validated in the CXCL16 neutralizing antibody asthma model.

CONCLUSION

A comprehensive biological analysis of the lncRNA-mRNA co-expression network explored key genes and pathways, providing new insights for understanding their mechanisms and discovering new targets for asthma induced by . The four differentially expressed key lncRNAs in the co-expression network (NONMMUT026034, NONMMUT028184, NONMMUT016537, and NONMMUT043155) can serve as intervention targets for CXCL16 molecular regulation of antigen presentation in mice asthma models.

摘要

目的

基于长链非编码RNA(lncRNA)和mRNA表达谱,研究CXCL16分子相关(提取物诱导的抗原呈递)在小鼠哮喘模型中的调控机制。

方法

通过气管内滴注给予敲除小鼠和野生型小鼠提取物以诱导哮喘气道炎症。利用高通量芯片测序筛选两组肺组织中lncRNA和mRNA表达谱差异。通过基因本体论(GO)和京都基因与基因组百科全书(KEGG)通路富集分析构建lncRNA-mRNA共表达网络。给野生型小鼠腹腔注射CXCL16中和抗体,并使用逆转录聚合酶链反应(RT-PCR)和酶联免疫吸附测定(ELISA)验证生物信息学和炎症结果。

结果

与野生型小鼠相比,CXCL16敲除小鼠肺组织中有120种lncRNA和388种mRNA上调,而1984种lncRNA和301种mRNA下调。构建的lncRNA-mRNA共表达网络包括244种差异表达的lncRNA和49种差异表达的mRNA。其中,在CXCL16中和抗体哮喘模型中验证了核心网络中枢纽基因异柠檬酸脱氢酶1(Idh1)和前四种lncRNA的表达。

结论

对lncRNA-mRNA共表达网络进行全面的生物学分析,探索了关键基因和通路,为理解其机制和发现提取物诱导哮喘的新靶点提供了新见解。共表达网络中四个差异表达的关键lncRNA(NONMMUT026034、NONMMUT028184、NONMMUT016537和NONMMUT043155)可作为小鼠哮喘模型中CXCL16分子调节抗原呈递的干预靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0fd5/11681907/e126a6457063/JIR-17-11561-g0001.jpg

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