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构建和综合分析ceRNA网络以揭示良性气管狭窄的关键基因

Construction and Comprehensive Analysis of the ceRNA Network to Reveal Key Genes for Benign Tracheal Stenosis.

作者信息

He Yanpeng, Zou Chunyan, Cai Zhigang

机构信息

The First Department of Pulmonary and Critical Care Medicine, The Second Hospital of Hebei Medical University, Heibei Key Laboratory of Respiratory Critical Care, Shijiazhuang, China.

Department of Pulmonary and Critical Care Medicine, The First Hospital of Qinhuangdao, Qinhuangdao, China.

出版信息

Front Genet. 2022 Jun 23;13:891741. doi: 10.3389/fgene.2022.891741. eCollection 2022.

Abstract

To explore the possible biological functions of the differentially expressed genes in patients with benign tracheal stenosis, and to provide a valuable molecular basis for investigating the pathogenesis of benign tracheal stenosis. Whole transcriptome sequencing was performed on blood samples collected from patients with benign tracheal stenosis and normal controls. Differentially expressed mRNA, lncRNA, and circRNA were analyzed using the DESeq2 package. The protein interaction networks for differentially expressed mRNAs were constructed by STRING. The results of gene co-expression network analysis, Starbase database prediction, and differential gene expression were combined to construct a competing endogenous RNA network. The transcription factors of key genes were predicted using the Network Analyst database and a transcription factor-mRNA regulatory network was constructed. The classical pathways, intermolecular interaction networks, and upstream regulatory components of key genes were analyzed using Ingenuity Pathway Analysis (IPA). Finally, the DGIDB database was used to predict the potential therapeutic drugs to target the identified key genes. Based on mRNA, lncRNA and circRNA expression data, we found that differentially expressed mRNAs were enriched in oxygen transport, neutrophil activation, immune response, and oxygen binding. Then the pearson correlation between mRNAs of 46 key genes and lncRNAs and cricRNAs were calculated, and the correlation greater than 0.9 were selected to construct the co-expression network of "mRNA-lncRA" and "mRNA-cricRNA." Moreover, a "lncRNA-miRNA-mRNA" network and a "circRNA-miRNA-mRNA" network were constructed. IPA analysis showed that the 46 key genes were significantly associated with inflammatory activation and acute respiratory distress syndrome. The constructed TF-mRNA regulatory network was composed of 274 nodes and 573 interacting pairs. 251 potential therapeutic drugs were identified from the DGIDB database. This study analyzed the differential genes associated with benign tracheal stenosis and explored the potential regulatory mechanisms, providing a scientific reference for further studies on the pathogenesis of benign tracheal stenosis.

摘要

为探究良性气管狭窄患者中差异表达基因的可能生物学功能,并为研究良性气管狭窄的发病机制提供有价值的分子基础。对收集自良性气管狭窄患者和正常对照的血样进行全转录组测序。使用DESeq2软件包分析差异表达的mRNA、lncRNA和circRNA。通过STRING构建差异表达mRNA的蛋白质相互作用网络。结合基因共表达网络分析结果、Starbase数据库预测结果和差异基因表达构建竞争性内源RNA网络。使用Network Analyst数据库预测关键基因的转录因子并构建转录因子-mRNA调控网络。利用 Ingenuity Pathway Analysis (IPA) 分析关键基因的经典通路、分子间相互作用网络和上游调控成分。最后,使用DGIDB数据库预测靶向已鉴定关键基因的潜在治疗药物。基于mRNA、lncRNA和circRNA表达数据,我们发现差异表达的mRNA富集于氧转运、中性粒细胞活化、免疫反应和氧结合。然后计算46个关键基因的mRNA与lncRNA和circRNA之间的皮尔逊相关性,选择相关性大于0.9的构建“mRNA-lncRA”和“mRNA-circRNA”共表达网络。此外,构建了“lncRNA-miRNA-mRNA”网络和“circRNA-miRNA-mRNA”网络。IPA分析表明,46个关键基因与炎症激活和急性呼吸窘迫综合征显著相关。构建的TF-mRNA调控网络由274个节点和573个相互作用对组成。从DGIDB数据库中鉴定出251种潜在治疗药物。本研究分析了与良性气管狭窄相关的差异基因,探索了潜在调控机制,为进一步研究良性气管狭窄的发病机制提供了科学参考。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7feb/9261475/8cfddd933601/fgene-13-891741-g001.jpg

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