AUTHOR=Li Chuan Xing , Gao Jing , Sköld C. Magnus , Wheelock Åsa M. 

TITLE=miRNA–mRNA–protein dysregulated network in COPD in women

JOURNAL=Frontiers in Genetics

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2022.1010048

DOI=10.3389/fgene.2022.1010048

ISSN=1664-8021

ABSTRACT=<p><bold>Rationale:</bold> Chronic obstructive pulmonary disease (COPD) is a complex disease caused by a multitude of underlying mechanisms, and molecular mechanistic modeling of COPD, especially at a multi-molecular level, is needed to facilitate the development of molecular diagnostic and prognostic tools and efficacious treatments.</p><p><bold>Objectives:</bold> To investigate the miRNA–mRNA–protein dysregulated network to facilitate prediction of biomarkers and disease subnetwork in COPD in women.</p><p><bold>Measurements and Results:</bold> Three omics data blocks (mRNA, miRNA, and protein) collected from BAL cells from female current-smoker COPD patients, smokers with normal lung function, and healthy never-smokers were integrated with miRNA–mRNA–protein regulatory networks to construct a COPD-specific dysregulated network. Furthermore, downstream network topology, literature annotation, and functional enrichment analysis identified both known and novel disease-related biomarkers and pathways. Both abnormal regulations in miRNA-induced mRNA transcription and protein translation repression play roles in COPD. Finally, the let-7-AIFM1-FKBP1A pathway is highlighted in COPD pathology.</p><p><bold>Conclusion:</bold> For the first time, a comprehensive miRNA–mRNA–protein dysregulated network of primary immune cells from the lung related to COPD in females was constructed to elucidate specific biomarkers and disease pathways. The multi-omics network provides a new molecular insight from a multi-molecular aspect and highlights dysregulated interactions. The highlighted let-7-AIFM1-FKBP1A pathway also indicates new hypotheses of COPD pathology.</p>