Identification and Validation of CDKN1A and HDAC1 as Senescence-Related Hub Genes in Chronic Obstructive Pulmonary Disease.

Int J Chron Obstruct Pulmon Dis

Department of Pulmonary and Critical Care Medicine, Qilu Hospital of Shandong University, Shandong Key Laboratory of Infectious Respiratory Diseases, Jinan, People's Republic of China.

Published: August 2022

AI Article Synopsis

  • - The study investigates how cellular senescence affects chronic obstructive pulmonary disease (COPD) and aims to find important genes that could serve as diagnostic markers or treatment targets for the condition.
  • - Researchers used microarray data to identify 23 genes related to cellular senescence in COPD patients and performed various analyses to determine their functions and interactions, ultimately pinpointing four key genes.
  • - The two validated hub genes, CDKN1A and HDAC1, showed correlations with lung function and could be promising candidates for developing new diagnostic and therapeutic strategies for COPD.

Article Abstract

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. CDKN1A and HDAC1 were verified as final hub genes based on GSE100281 and GSE103174 datasets validation. The mRNA expression level of CDKN1A was negatively related to forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC), and HDAC1 expression had the opposite correlation. Finally, an HDAC1-based ceRNA network, including 6 miRNAs and 11 lncRNAs, was constructed.

Conclusion: We identified two senescence-related hub genes, CDKN1A and HDAC1, which may be effective biomarkers for COPD diagnosis and treatment. An HDAC1-related ceRNA network was constructed to clarify the role of senescence in COPD pathogenesis.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9375999PMC
http://dx.doi.org/10.2147/COPD.S374684DOI Listing

Publication Analysis

Top Keywords

hub genes
28
cdkn1a hdac1
12
senescence-related hub
12
cerna network
12
genes
11
chronic obstructive
8
obstructive pulmonary
8
pulmonary disease
8
gse38974 dataset
8
network constructed
8

Similar Publications

Background: Bioinformatics analysis of hepatocellular carcinoma (HCC) expression profiles can aid in understanding its molecular mechanisms and identifying new targets for diagnosis and treatment.

Aim: In this study, we analyzed expression profile datasets and miRNA expression profiles related to HCC from the GEO using R software to detect differentially expressed genes (DEGs) and differentially expressed miRNAs (DEmiRs).

Methods And Results: Common DEGs were identified, and a PPI network was constructed using the STRING database and Cytoscape software to identify hub genes.

View Article and Find Full Text PDF

Background: Post-stroke depression (PSD) is the most prevalent neuropsychiatric complication following a stroke. The inflammatory theory suggests that PSD may be associated with an overactive inflammatory response. However, research findings regarding inflammation-related indicators in PSD remain inconsistent and elusive.

View Article and Find Full Text PDF

Background: Sepsis is an uncontrolled reaction to infection that causes severe organ dysfunction and is a primary cause of ARDS. Patients suffering both sepsis and ARDS have a poor prognosis and high mortality. However, the mechanisms behind their simultaneous occurrence are unclear.

View Article and Find Full Text PDF

Gene‒gene interactions play pivotal roles in disease pathogenesis and are fundamental in the development of targeted therapeutics, particularly through the elucidation of oncogenic gene drivers in cancer. The systematic analysis of pathways and gene interactions is critical in the drug discovery process for various cancer subtypes. SPAG5, known for its role in spindle formation during cell division, has been identified as an oncogene in several cancers, although its specific impact on AML remains underexplored.

View Article and Find Full Text PDF

Single-Cell RNA sequencing reveals mitochondrial dysfunction in microtia chondrocytes.

Sci Rep

January 2025

Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Microtia is a congenital malformation characterized by underdevelopment of the external ear. While chondrocyte dysfunction has been implicated in microtia, the specific cellular abnormalities remain poorly understood. This study aimed to investigate mitochondrial dysfunction in microtia chondrocytes using single-cell RNA sequencing.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!