Identification and Validation of CDKNIA and HDACI as Senescence-Related Hub Genes in Chronic Obstructive Pulmonary Disease

Purpose: Cellular senescence participates in the occurrence and development of chronic obstructive pulmonary disease (COPD). This study aimed to identify senescence-related hub genes and explore effective diagnostic markers and therapeutic targets for COPD. Methods: The microarray data from the GSE3...

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Bibliographic Details
Published in:International journal of chronic obstructive pulmonary disease 2022-08, Vol.17, p.1811
Main Authors: Yang, Jie, Zhang, Meng-Yu, Du, Yi-Ming, Ji, Xiu-Li, Qu, Yi-Qing
Format: Article
Language:English
Subjects:
Genes
Genetic transcription
Genomes
Genomics
Health aspects
Lung diseases, Obstructive
Medical research
Medicine, Experimental
MicroRNA
Protein-protein interactions
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Summary:Purpose: Cellular senescence participates in the occurrence and development of chronic obstructive pulmonary disease (COPD). This study aimed to identify senescence-related hub genes and explore effective diagnostic markers and therapeutic targets for COPD. Methods: The microarray data from the GSE38974 dataset was downloaded from the Gene Expression Omnibus (GEO) database. The overlapping genes between genes from the GSE38974 dataset and CellAge database were considered differentially expressed senescence-related genes (DESRGs). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed using R software. Protein-protein interaction (PPI), miRNA-mRNA network, and competitive endogenous RNA (ceRNA) network were constructed and visualized by Cytoscape software. GSE100281 and GSE103174 datasets were employed to validate the expression and diagnostic value of hub genes. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to measure the mRNA levels of hub genes in peripheral blood mononuclear cells (PBMCs) from COPD and control samples. Results: A total of 23 DESRGs were identified between COPD samples and healthy controls. Enrichment analysis revealed that DESRGs were mainly related to apoptosis and senescence. Moreover, four hub genes and two key clusters were acquired by Cytohubba and MCODE plugin, respectively. CDKNIA and HDACI were verified as final hub genes based on GSE100281 and GSE103174 datasets validation. The mRNA expression level of CDKNIA was negatively related to forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC), and HDACI expression had the opposite correlation. Finally, an HDAC1-based ceRNA network, including 6 miRNAs and 11 IncRNAs, was constructed. Conclusion: We identified two senescence-related hub genes, CDKNIA and HDACI, which may be effective biomarkers for COPD diagnosis and treatment. An HDACI-related ceRNA network was constructed to clarify the role of senescence in COPD pathogenesis. Keywords: chronic obstructive pulmonary disease, senescence, bioinformatics, CDKNIA, HDACI
ISSN:1178-2005
DOI:10.2147/COPD.S374684