Analysis of Communal Molecular Mechanism Between Chronic Obstructive Pulmonary Disease and Osteoporosis

Abstract

Background

Chronic obstructive pulmonary disease (COPD) patients with osteoporosis (OP) usually experience more frequent exacerbations, worse quality of life, and heavier economic burden, however, few studies have investigated common molecular mechanisms of COPD and OP.

Objective

To explore the relationship between COPD and OP through bioinformatics analysis.

Methods

The miRNA microarray data of COPD and OP were retrieved from the Gene Expression Database (GEO), and the differentially expressed microRNAs (DEmiRNAs) were screened and the intersection was obtained. The Targetscan, miRDB, and miRWalk databases were used to predict the target genes of DEmiRNA, and the gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed using the R package clusterProfiler, the STRING database was used to analyze the target protein–protein interaction network (PPI) and screens to determine the core modules and core genes.

Results

Two DEmiRNAs (miR-23a-5p, miR-194-3p) have been found in COPD and OP, which have predicted 76 and 114 target genes, respectively. GO functional annotations of miR-23a-5p were significantly enriched in CD40 signaling pathway, ubiquitin-conjugating enzyme activity, etc; KEGG pathways of miR-23a-5p were significantly enriched in ubiquitin-mediated proteolysis, folate biosynthesis, and regulation of actin cytoskeleton. GO function annotations of miR-194-3p were significantly enriched in T cell activation regulation, ubiquitin protein ligase activity, and DNA transcription factor binding; KEGG pathways of miR-194-3p were significantly enriched in cell adhesion molecules, intercellular tight junctions, and lysosomal pathway. PPI analysis found target coding proteins formed complex regulatory networks. Ten core genes (TP53, SRC, PXN, CHD4, SYK, TNRC6B, PML, KAT5, BRD1 and IGF2) were picked out among them, then we used the MCODE plugin found three core subnetworks.

Conclusion

Two identical DEmiRNAs (miR-23a-5p, miR-194-3p) exist in the peripheral blood of COPD and OP patients, which are important biomarkers for COPD patients with OP and may represent novel targets for diagnosis and treatment of COPD patients with OP.

Keywords:

• chronic obstructive pulmonary disease
• osteoporosis
• bioinformatics
• microRNA

Abbreviations

COPD, chronic obstructive pulmonary disease; OP, osteoporosis; GEO, Gene Expression Database; DEmiRNAs, differentially expressed microRNAs; GO, gene ontology; KEGG, Kyoto Encyclopedia of Genes and Genomes; mRNA, messenger RNA; FC, fold change; PPI, protein–protein interaction; BMI, body mass index; BMD, bone mineral density; 25(OH)D, 25-hydroxy vitamin D; DAPK1, death-associated protein kinase 1; SNP, single-nucleotide polymorphism; OPG, osteoprotegerin; MSC, mesenchymal stem cell; PXN, paxillin; HCys, homocysteine; ECM, extracellular matrix; Syk, spleen tyrosine kinase.

Data Sharing Statement

The data will be available from the corresponding author on reasonable request.

Ethics Approval

Because this study did not involve human subjects or samples; it was deemed negligible-risk research and was exempt from ethical review by the Ethics Committee of The First Hospital of Lanzhou University, thus, no consent was required.

Acknowledgments

The authors would like to thank the GEO database for supporting the study with its data resources.

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 have no conflicts of interest to declare.

Additional information

Funding

This work was supported by the National Natural Science Foundation of China (Grant No. 81960009).