Identification of Putative Regulatory Alterations Leading to Changes in Gene Expression in Chronic Obstructive Pulmonary Disease
Dong-Yeop Kim1, Woo Jin Kim2, Jung-Hyun Kim2, Seok-Ho Hong2, and Sun Shim Choi1,*
1Division of Biomedical Convergence, College of Biomedical Science, Institute of Bioscience & Biotechnology, 2Department of Internal Medicine, School of Medicine, Kangwon National University, Chuncheon 24341, Korea
Received November 30, 2018; Revised January 23, 2019; Accepted February 12, 2019.; Published online March 26, 2019.
© Korean Society for Molecular and Cellular Biology. All rights reserved.

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ABSTRACT
Various genetic and environmental factors are known to be associated with chronic obstructive pulmonary disease (COPD). We identified COPD-related differentially expressed genes (DEGs) using 189 samples accompanying either adenocarcinoma (AC) or squamous cell carcinoma (SC), comprising 91 normal and 98 COPD samples. DEGs were obtained from the intersection of two DEG sets separately identified for AC and SC to exclude the influence of different cancer backgrounds co-occurring with COPD. We also measured patient samples named group ‘I’, which were unable to be determined as normal or COPD based on alterations in gene expression. The Gene Ontology (GO) analysis revealed significant alterations in the expression of genes categorized with the ‘cell adhesion’, ‘inflammatory response’, and ‘mitochondrial functions’, i.e., well-known functions related to COPD, in samples from patients with COPD. Multi-omics data were subsequently integrated to decipher the upstream regulatory changes linked to the gene expression alterations in COPD. COPD-associated expression quantitative trait loci (eQTLs) were located at the upstream regulatory regions of 96 DEGs. Additionally, 45 previously identified COPD-related miRNAs were predicted to target 66 of the DEGs. The eQTLs and miRNAs might affect the expression of ‘respiratory electron transport chain’ genes and ‘cell proliferation’ genes, respectively, while both eQTLs and miRNAs might affect the expression of ‘apoptosis’ genes. We think that our present study will contribute to our understanding of the molecular etiology of COPD accompanying lung cancer.
Keywords: COPD, differentially expressed genes, lung cancer, regulatory alterations, STX8


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31 March 2019 Volume 42,
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