ceRNA Network Analysis Reveals Potential Key miRNAs and Target Genes in COVID-19-Related Chronic Obstructive Pulmonary Disease

Abstract

The continued spread of SARS-CoV-2 has presented unprecedented obstacles to the worldwide public health system. Especially, individuals with chronic obstructive pulmonary disease (COPD) are at a heightened risk of contracting SARS-CoV-2 infection due to their pre-existing respiratory symptoms that are not well-managed. However, the viral mechanism of affecting the expression of host genes, COPD progression, and prognosis is not clear yet.This study integrated the differential expression information of COPD patients and then calculated the correlation between mRNAs and miRNAs to construct a COPD-specific ceRNA network. The DEGs of individuals with SARS-CoV-2 infection and anticipated miRNAs and their targets were analyzed in 9 SARS-CoV-2 sequences from different geographic locations. Furthermore, combining the experimentally validated miRNAs and genes, the regulatory miRNA-mRNA relationships were identified. All the regulatory relationships were integrated into the COPD-specific network and the network modules were explored to get insight into the functional mechanism of SARS-CoV-2 infection in COPD patients.A higher proportion of DEGs compete with the same miRNA suggesting a higher expression of genes in the COPD-specific ceRNA network. Hsa-miR-21-3p is the largest connected point in the network, but the proportion of genes upregulated by hsa-miR-21-3p is low (P = 0.1406). This indicates that the regulatory relationship of competitive inhibition has little effect on has-miR-21, and the high expression pattern is a poor prognostic factor in COPD. Hsa-miR-15a-5p is the most significant miRNA with the highest proportion of DEGs. And ANXA2P3 is the only gene in the COPD ceRNA network that interferes with hsa-miR-15a-5p. In addition, we found that has-miR-1184- and has-miR-99-cored modules were significant, and genes ZDHHC18, PCGF3, and KIAA0319L interacting with them were all associated with COPD prognosis, and high expression of these genes could lead to poor prognosis in COPD.The key regulators such as miR-21, miR-15a, ANXA2P3, ZDHHC18, PCGF3, and KIAA0319L can be used as prognostic biomarkers for early intervention in COPD with SARS-CoV-2 infection.

Keywords: Chronic obstructive pulmonary disease (COPD); Covid-related COPD; Micro-RNA; Network analysis; RNA-based regulation.