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miR-34b/c-5p/CXCL10 Axis Induced by RSV Infection Mediates a Mechanism of Airway Hyperresponsive Diseases

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 differe...

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Autores principales: Liu, Dan, Tang, Zhongxiang, Bajinka, Ousman, Dai, Pei, Wu, Guojun, Qin, Ling, Tan, Yurong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9953223/
https://www.ncbi.nlm.nih.gov/pubmed/36829591
http://dx.doi.org/10.3390/biology12020317
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author Liu, Dan
Tang, Zhongxiang
Bajinka, Ousman
Dai, Pei
Wu, Guojun
Qin, Ling
Tan, Yurong
author_facet Liu, Dan
Tang, Zhongxiang
Bajinka, Ousman
Dai, Pei
Wu, Guojun
Qin, Ling
Tan, Yurong
author_sort Liu, Dan
collection PubMed
description 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.
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spelling pubmed-99532232023-02-25 miR-34b/c-5p/CXCL10 Axis Induced by RSV Infection Mediates a Mechanism of Airway Hyperresponsive Diseases Liu, Dan Tang, Zhongxiang Bajinka, Ousman Dai, Pei Wu, Guojun Qin, Ling Tan, Yurong Biology (Basel) Article 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. MDPI 2023-02-16 /pmc/articles/PMC9953223/ /pubmed/36829591 http://dx.doi.org/10.3390/biology12020317 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Liu, Dan
Tang, Zhongxiang
Bajinka, Ousman
Dai, Pei
Wu, Guojun
Qin, Ling
Tan, Yurong
miR-34b/c-5p/CXCL10 Axis Induced by RSV Infection Mediates a Mechanism of Airway Hyperresponsive Diseases
title miR-34b/c-5p/CXCL10 Axis Induced by RSV Infection Mediates a Mechanism of Airway Hyperresponsive Diseases
title_full miR-34b/c-5p/CXCL10 Axis Induced by RSV Infection Mediates a Mechanism of Airway Hyperresponsive Diseases
title_fullStr miR-34b/c-5p/CXCL10 Axis Induced by RSV Infection Mediates a Mechanism of Airway Hyperresponsive Diseases
title_full_unstemmed miR-34b/c-5p/CXCL10 Axis Induced by RSV Infection Mediates a Mechanism of Airway Hyperresponsive Diseases
title_short miR-34b/c-5p/CXCL10 Axis Induced by RSV Infection Mediates a Mechanism of Airway Hyperresponsive Diseases
title_sort mir-34b/c-5p/cxcl10 axis induced by rsv infection mediates a mechanism of airway hyperresponsive diseases
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9953223/
https://www.ncbi.nlm.nih.gov/pubmed/36829591
http://dx.doi.org/10.3390/biology12020317
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