Liu Dan, Tang Zhongxiang, Bajinka Ousman, Dai Pei, Wu Guojun, Qin Ling, Tan Yurong
Department of Medical Microbiology, School of Basic Medical Sciences, Central South University, Changsha 410078, China.
Department of Respiratory Medicine, National Key Clinical Specialty, Branch of National Clinical Research Center for Respiratory Disease, Central South University, Changsha 410078, China.
Biology (Basel). 2023 Feb 16;12(2):317. doi: 10.3390/biology12020317.
RSV is closely correlated with post-infection airway hyperresponsive diseases (AHD), but the mechanism remains unclear. Due to the pivotal role of miRNAs in AHD, we analyzed the differentially expressed miRNAs (DEmiRs) in RSV-infected patients, asthma patients, and COPD patients from public datasets and explored the mechanisms of association between RSV and AHD. We obtained miRNA and mRNA databases of patients with RSV infection, as well as miRNA databases of asthma and COPD patients from the GEO database. Through integrated analysis, we screened DEmiRs and DEGs. Further analysis was carried out to obtain the hub genes through the analysis of biological pathways and enrichment pathways of DEGs targeted by DEmiRs and the construction of a protein-protein interaction (PPI) network. The five differential molecules (miR-34b/c-5p, Cd14, Cxcl10, and Rhoh) were verified through in vivo experiments that had the same expression trend in the acute and chronic phases of RSV infection. Following infection of BEAS-2B cells with RSV, we confirmed that RSV infection down-regulated miR-34b/c-5p, and up-regulated the expression levels of CXCL10 and CD14. Furthermore, the results of the dual-luciferase reporter assay showed that CXCL10 was the target of hsa-miR-34c-5p. miR-34b/c-5p/CXCL10 axis mediates a mechanism of AHD.
呼吸道合胞病毒（RSV）与感染后气道高反应性疾病（AHD）密切相关，但其机制尚不清楚。由于微小RNA（miRNA）在AHD中起关键作用，我们从公共数据集中分析了RSV感染患者、哮喘患者和慢性阻塞性肺疾病（COPD）患者中差异表达的miRNA（DEmiR），并探讨了RSV与AHD之间的关联机制。我们从基因表达综合数据库（GEO数据库）中获取了RSV感染患者的miRNA和mRNA数据库，以及哮喘和COPD患者的miRNA数据库。通过综合分析，我们筛选出了DEmiR和差异表达基因（DEG）。通过对DEmiR靶向的DEG的生物途径和富集途径进行分析，并构建蛋白质-蛋白质相互作用（PPI）网络，进一步分析以获得枢纽基因。通过体内实验验证了五个差异分子（miR-34b/c-5p、Cd14、Cxcl10和Rhoh）在RSV感染的急性期和慢性期具有相同的表达趋势。用RSV感染BEAS-2B细胞后，我们证实RSV感染下调了miR-34b/c-5p，并上调了CXCL10和CD14的表达水平。此外，双荧光素酶报告基因检测结果表明CXCL10是hsa-miR-34c-5p的靶标。miR-34b/c-5p/CXCL10轴介导了AHD的一种机制。
