LAUSR

Simple Summary Airway hyperresponsive diseases (AHD), such as asthma and chronic obstructive pulmonary disease (COPD), are a serious public health burden worldwide. Studies have shown that viral infection plays an important role in asthma and COPD, especially RSV. In this study, we analyzed differentially expressed miRNAs (DEmiRs) in RSV-infected patients, asthma patients, and COPD patients by screening miRNA profiling from public datasets. Integrated analysis was then performed with mRNA datasets obtained from RSV-infected patients. We found that miR-34b/c-5p was downregulated. In vivo and in vitro experiments confirmed that decreased hsa-miR-34b/c-5p expression induced CXCL10 secretion and promoted THP-1 derived macrophages chemotaxis. In addition, miR-34c-5p can bind directly to CXCL10. This study provides new insights into the molecular mechanism of hsa-miR-34b/c-5p/CXCL10 in airway inflammation and AHR. Abstract Background: RSV is closely correlated with post-infection airway hyperresponsive diseases (AHD), but the mechanism remains unclear. Objective: 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. Methods: 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. Results: 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. Conclusions: miR-34b/c-5p/CXCL10 axis mediates a mechanism of AHD.