Analysis of Key Genes and miRNA-mRNA Networks Associated with Glucocorticoids Treatment in Chronic Obstructive Pulmonary Disease

Abstract

Background

Some patients with chronic obstructive pulmonary disease (COPD) benefit from glucocorticoid (GC) treatment, but its mechanism is unclear.

Objective

With the help of the Gene Expression Omnibus (GEO) database, the key genes and miRNA-mRNA related to the treatment of COPD by GCs were discussed, and the potential mechanism was explained.

Methods

The miRNA microarray dataset (GSE76774) and mRNA microarray dataset (GSE36221) were downloaded, and differential expression analysis were performed. Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed on the differentially expressed genes (DEGs). The protein interaction network of the DEGs in the regulatory network was constructed with the STRING database, and the key genes were screened through Cytoscape. Potential downstream target genes regulated by differentially expressed miRNAs (DEMs) were predicted by the miRWalk3.0 database, and miRNA-mRNA regulatory networks were constructed. Finally, some research results were validated.

Results

① Four DEMs and 83 DEGs were screened; ② GO and KEGG enrichment analysis mainly focused on the PI3K/Akt signalling pathway, ECM receptor interaction, etc.; ③ CD2, SLAMF7, etc. may be the key targets of GC in the treatment of COPD; ④ 18 intersection genes were predicted by the mirwalk 3.0 database, and 9 pairs of miRNA-mRNA regulatory networks were identified; ⑤ The expression of miR-320d-2 and TFCP2L1 were upregulated by dexamethasone in the COPD cell model, while the expression of miR-181a-2-3p and SLAMF7 were downregulated.

Conclusion

In COPD, GC may mediate the expression of the PI3K/Akt signalling pathway through miR-181a-2-3p, miR-320d-2, miR-650, and miR-155-5p, targeting its downstream signal factors. The research results provide new ideas for RNA therapy strategies of COPD, and also lay a foundation for further research.

Keywords:

• COPD
• GC
• GEO database
• miRNA-mRNA
• DEMs
• DEGs

Abbreviations

COPD, chronic obstructive pulmonary disease; GC, glucocorticoid; GO, Gene ontology; KEGG, Kyoto encyclopedia of genes and genomes.

Data Sharing Statement

The data supporting the findings of this study are available within the article.

Ethics Approval and Informed Consent

This research was reviewed and permitted by the Scientific research ethics committee of the Third Affiliated Hospital of Beijing University of Chinese Medicine.

Author Contributions

ALL authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

The authors declare that they have no competing interests in this work.

Additional information

Funding

The work was supported by National Natural Science Foundation of China (grant numbers 82274462), Beijing Municipal Natural Science Foundation (grant numbers 7232284) and The Fifth Batch of National Excellent Clinical Talents of Traditional Chinese Medicine Research Project (National Administration of Traditional Chinese Medicine Renjiaoshi [2022] No. 1). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.