Research Paper Volume 14, Issue 10 pp 4336—4356
Identification and validation of aging-related genes in COPD based on bioinformatics analysis
- 1 Guangdong Key Laboratory of Epigenetics, College of Life Sciences and Oceanography, Shenzhen University, Shenzhen 518055, P.R. China
- 2 Key Laboratory of Optoelectronic Devices and Systems of Ministry of Education and Guangdong Province, College of Optoelectronic Engineering, Shenzhen University, Shenzhen 518061, P.R. China
- 3 Key Laboratory of Interventional Pulmonology of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325015, P.R. China
- 4 Longhua Innovation Institute for Biotechnology, College of Life Sciences and Oceanography, Shenzhen University, Shenzhen 518060, P.R. China
Received: October 18, 2021 Accepted: April 12, 2022 Published: May 24, 2022
https://doi.org/10.18632/aging.204064How to Cite
Copyright: © 2022 Zhong et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Chronic obstructive pulmonary disease (COPD) is a serious chronic respiratory disorder. One of the major risk factors for COPD progression is aging. Therefore, we investigated aging-related genes in COPD using bioinformatic analyses. Firstly, the Aging Atlas database containing 500 aging-related genes and the Gene Expression Omnibus database (GSE38974) were utilized to screen candidates. A total of 24 candidate genes were identified related to both COPD and aging. Using gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses, we found that this list of 24 genes was enriched in genes associated with cytokine activity, cell apoptosis, NF-κB and IL-17 signaling. Four of these genes (CDKN1A, HIF1A, MXD1 and SOD2) were determined to be significantly upregulated in clinical COPD samples and in cigarette smoke extract-exposed Beas-2B cells in vitro, and their expression was negatively correlated with predicted forced expiratory volume and forced vital capacity. In addition, the combination of expression levels of these four genes had a good discriminative ability for COPD patients (AUC = 0.794, 95% CI 0.743–0.845). All four were identified as target genes of hsa-miR-519d-3p, which was significantly down-regulated in COPD patients. The results from this study proposed that regulatory network of hsa-miR-519d-3p/CDKN1A, HIF1A, MXD1, and SOD2 closely associated with the progression of COPD, which provides a theoretical basis to link aging effectors with COPD progression, and may suggest new diagnostic and therapeutic targets of this disease.