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Integrative Analysis Reveals a miRNA-mRNA Regulatory Network and Potential Causative Agents in the Asthmatic Airway Epithelium

BACKGROUND: During asthma progression, the intricate molecular networks, including microRNA (miRNA) transcriptional regulation in airway epithelium, remain largely undefined. The abnormal expression of miRNAs in asthmatic airway epithelium is a recent and fast-growing area in developing diagnostic a...

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Autores principales: Zhang, Jintao, Wang, Zihan, Zhang, Dong, Pan, Yun, Liu, Xiaofei, Qiao, Xinrui, Cui, Wenjing, Dong, Liang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8566008/
https://www.ncbi.nlm.nih.gov/pubmed/34744440
http://dx.doi.org/10.2147/JAA.S331090
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author Zhang, Jintao
Wang, Zihan
Zhang, Dong
Pan, Yun
Liu, Xiaofei
Qiao, Xinrui
Cui, Wenjing
Dong, Liang
author_facet Zhang, Jintao
Wang, Zihan
Zhang, Dong
Pan, Yun
Liu, Xiaofei
Qiao, Xinrui
Cui, Wenjing
Dong, Liang
author_sort Zhang, Jintao
collection PubMed
description BACKGROUND: During asthma progression, the intricate molecular networks, including microRNA (miRNA) transcriptional regulation in airway epithelium, remain largely undefined. The abnormal expression of miRNAs in asthmatic airway epithelium is a recent and fast-growing area in developing diagnostic and therapeutic targets for asthma. MATERIAL AND METHODS: Analyses were conducted to compare airway epithelial miRNAs and gene expression between patients with asthma and healthy subjects from three datasets (two for miRNAs expression profiles and one for gene expression profile). The interactions network between differentially expressed (DE)-miRNAs and mRNAs was further identified for functional analysis. To verify the involvement and functions of all the identified miRNAs in asthma, we constructed two cellular models of asthma. The most promising causal miRNA candidate, miR-1246, was examined in an in vitro system to explore its targets and roles in asthma pathophysiology. RESULTS: Through integrative analysis, we obtained six miRNAs with 31 validated target genes in airway epithelium associated with asthma. Next, we confirmed that these miRNAs were all associated with asthma progression by in vitro functional experiments. They may participate in eosinophilic inflammation (miR-92b-3p, miR-1246, miR-197-3p, and miR-124-5p) or remodeling (miR-197-3p, miR-193a-5p, miR-1246, and miR-92b-3p). Additionally, some other non-screened valuable miRNAs were also examined and identified (miR-21-5p and miR-19b-3p), and some detected in blood correlated with the disease status. Furthermore, we found that miR-1246 could directly target POSTN and influence epithelial-to-mesenchymal transition and fibrosis in airway epithelial cells. CONCLUSION: We constructed a preliminary epithelial regulatory network in asthma based on six identified miRNAs and their valuable target genes. Candidate factors in the biological miRNA-mRNA network in airway epithelium may provide further information on the pathogenesis of asthma. Strikingly, among all screened miRNAs, miR-1246, which could interact with POSTN may have multifunctional effects in the course of asthma and be a promising agent for asthma treatment and molecular subtyping.
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spelling pubmed-85660082021-11-05 Integrative Analysis Reveals a miRNA-mRNA Regulatory Network and Potential Causative Agents in the Asthmatic Airway Epithelium Zhang, Jintao Wang, Zihan Zhang, Dong Pan, Yun Liu, Xiaofei Qiao, Xinrui Cui, Wenjing Dong, Liang J Asthma Allergy Original Research BACKGROUND: During asthma progression, the intricate molecular networks, including microRNA (miRNA) transcriptional regulation in airway epithelium, remain largely undefined. The abnormal expression of miRNAs in asthmatic airway epithelium is a recent and fast-growing area in developing diagnostic and therapeutic targets for asthma. MATERIAL AND METHODS: Analyses were conducted to compare airway epithelial miRNAs and gene expression between patients with asthma and healthy subjects from three datasets (two for miRNAs expression profiles and one for gene expression profile). The interactions network between differentially expressed (DE)-miRNAs and mRNAs was further identified for functional analysis. To verify the involvement and functions of all the identified miRNAs in asthma, we constructed two cellular models of asthma. The most promising causal miRNA candidate, miR-1246, was examined in an in vitro system to explore its targets and roles in asthma pathophysiology. RESULTS: Through integrative analysis, we obtained six miRNAs with 31 validated target genes in airway epithelium associated with asthma. Next, we confirmed that these miRNAs were all associated with asthma progression by in vitro functional experiments. They may participate in eosinophilic inflammation (miR-92b-3p, miR-1246, miR-197-3p, and miR-124-5p) or remodeling (miR-197-3p, miR-193a-5p, miR-1246, and miR-92b-3p). Additionally, some other non-screened valuable miRNAs were also examined and identified (miR-21-5p and miR-19b-3p), and some detected in blood correlated with the disease status. Furthermore, we found that miR-1246 could directly target POSTN and influence epithelial-to-mesenchymal transition and fibrosis in airway epithelial cells. CONCLUSION: We constructed a preliminary epithelial regulatory network in asthma based on six identified miRNAs and their valuable target genes. Candidate factors in the biological miRNA-mRNA network in airway epithelium may provide further information on the pathogenesis of asthma. Strikingly, among all screened miRNAs, miR-1246, which could interact with POSTN may have multifunctional effects in the course of asthma and be a promising agent for asthma treatment and molecular subtyping. Dove 2021-10-30 /pmc/articles/PMC8566008/ /pubmed/34744440 http://dx.doi.org/10.2147/JAA.S331090 Text en © 2021 Zhang et al. https://creativecommons.org/licenses/by-nc/3.0/This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/ (https://creativecommons.org/licenses/by-nc/3.0/) ). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php).
spellingShingle Original Research
Zhang, Jintao
Wang, Zihan
Zhang, Dong
Pan, Yun
Liu, Xiaofei
Qiao, Xinrui
Cui, Wenjing
Dong, Liang
Integrative Analysis Reveals a miRNA-mRNA Regulatory Network and Potential Causative Agents in the Asthmatic Airway Epithelium
title Integrative Analysis Reveals a miRNA-mRNA Regulatory Network and Potential Causative Agents in the Asthmatic Airway Epithelium
title_full Integrative Analysis Reveals a miRNA-mRNA Regulatory Network and Potential Causative Agents in the Asthmatic Airway Epithelium
title_fullStr Integrative Analysis Reveals a miRNA-mRNA Regulatory Network and Potential Causative Agents in the Asthmatic Airway Epithelium
title_full_unstemmed Integrative Analysis Reveals a miRNA-mRNA Regulatory Network and Potential Causative Agents in the Asthmatic Airway Epithelium
title_short Integrative Analysis Reveals a miRNA-mRNA Regulatory Network and Potential Causative Agents in the Asthmatic Airway Epithelium
title_sort integrative analysis reveals a mirna-mrna regulatory network and potential causative agents in the asthmatic airway epithelium
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8566008/
https://www.ncbi.nlm.nih.gov/pubmed/34744440
http://dx.doi.org/10.2147/JAA.S331090
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