Prediction of key genes and miRNAs responsible for loss of muscle force in patients during an acute exacerbation of chronic obstructive pulmonary disease

Abstract

The present study aimed to identify genes and microRNAs (miRNAs or miRs) that were abnormally expressed in the vastus lateralis muscle of patients with acute exacerbations of chronic obstructive pulmonary disease (AECOPD). The gene expression profile of GSE10828 was downloaded from the Gene Expression Omnibus database, and this dataset was comprised of 4 samples from patients with AECOPD and 5 samples from patients with stable COPD. Differentially expressed genes (DEGs) were screened using the Limma package in R. A protein‑protein interaction (PPI) network of DEGs was built based on the STRING database. Module analysis of the PPI network was performed using the ClusterONE plugin and functional analysis of DEGs was conducted using DAVID. Additionally, key miRNAs were enriched using gene set enrichment analysis (GSEA) software and a miR-gene regulatory network was constructed using Cytoscape software. In total, 166 up- and 129 downregulated DEGs associated with muscle weakness in AECOPD were screened. Among them, NCL, GOT1, TMOD1, TSPO, SOD2, NCL and PA2G4 were observed in the modules consisting of upregulated or downregulated genes. The upregulated DEGs in modules (including KLF6 and XRCC5) were enriched in GO terms associated with immune system development, whereas the downregulated DEGs were enriched in GO terms associated with cell death and muscle contraction. Additionally, 39 key AECOPD‑related miRNAs were also predicted, including miR-1, miR-9 and miR-23a, miR-16 and miR-15a. In conclusion, DEGs (NCL, GOT1, SOD2, KLF6, XRCC5, TSPO and TMOD1) and miRNAs (such as miR-1, miR-9 and miR-23a) may be associated with the loss of muscle force in patients during an acute exacerbation of COPD which also may act as therapeutic targets in the treatment of AECOPD.

Figure 1

Cascade figure of the normalization expression value. (A) Data before normalization. (B) Data after normalization. Green represents samples from patients with acute exacerbations of chronic obstructive pulmonary disease (AECOPD); red represents samples from patients with stable COPD.

Figure 2

Hierarchical clustering heat maps of differentially expressed genes (DEGs). The gradient color from green to red represents the expression level [acute chronic obstructive pulmonary disease (COPD) sample and stable COPD samples changes from upregulation to downregulation].

Figure 3

Protein-protein interaction (PPI) network of differentially expressed genes (DEGs).

Figure 4

Significant modules of differentially expressed genes (DEGs) in the protein-protein interaction (PPI) network. (A) Three modules for the upregulated DEGs, (B) three modules for the downregulated DEGs. Red nodes stand for the upregulated DEGs while blue nodes represent downregulated DEGs. Edges stand for the protein interaction and dot circle stand for the modules.

Figure 5

The miRNA regulatory network. Blue represents miRNA; red represents upregulated differentially expressed genes (DEGs); green represents downregulated DEGs.