Differential microRNA expression in the peripheral blood from human patients with COVID-19

Abstract

Introduction: The coronavirus disease (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which play important roles in regulating gene expression and are also considered as essential modulators during viral infection. The aim of this study was to elucidate the differential expression of miRNAs in COVID-19.

Methods: The total RNA was extracted and purified from the peripheral blood of ten patients with COVID-19 and four healthy donors. The expression levels of various miRNAs were detected by high-throughput sequencing, and correlation analysis was performed on the target genes that are primed by miRNAs.

Key findings: Compared with the healthy controls, 35 miRNAs were upregulated and 38 miRNAs were downregulated in the human patients with COVID-19. The top 10 genes were listed below: hsa-miR-16-2-3P,hsa-miR-5695,hsa-miR-10399-3P,hsa-miR-6501-5P,hsa-miR-361-3P,hsa-miR-361-3p, hsa-miR-4659a-3p, hsa-miR-142-5p, hsa-miR-4685-3p, hsa-miR-454-5p, and hsa-miR-30c-5p. The 10 genes with the greatest reduction were listed below: hsa-miR-183-5p, hsa-miR-627-5p, hsa-miR-941, hsa-miR-21-5p, hsa-miR-20a-5p, hsa-miR-146b-5p, hsa-miR-454-3p, hsa-miR-18a-5p, hsa-miR-340-5p, and hsa-miR-17-5p. Remarkably, miR-16-2-3p was the most upregulated miRNA, with a 1.6-fold change compared to that of the controls. Moreover, the expression of miR-6501-5p and miR-618 was 1.5-fold higher in the COVID-19 patients than in the healthy donors. Meanwhile, miR-627-5p was the most downregulated miRNA, with a 2.3-fold change compared to that of the controls. The expression of other miRNAs (miR-183-5p, miR-627-5p, and miR-144-3p) was reduced by more than 1.3-fold compared to that of the healthy donors. Cluster analysis revealed that all of the differentially expressed miRNA target genes were clustered by their regulation of cellular components, molecular functions, and biological processes. Importantly, peptidases, protein kinases, and the ubiquitin system were shown to be the highest enrichment categories by enrichment analysis.

Conclusions: The differential miRNA expression found in COVID-19 patients may regulate the immune responses and viral replication during viral infection.

Keywords: Bioinformatics analysis; COVID-19; high-throughput sequencing; microRNA.

© 2020 The Authors. Journal of Clinical Laboratory Analysis Published by Wiley Periodicals LLC.

Figures

Figure 1

Differential miRNA expression between COVID‐19 patients and healthy donors. Each point in the figure represents a gene, and the abscissa represents the logarithmic value logFC of the multiple differences of gene expression between the two groups. The ordinate represents the negative pair value of the p‐value of the change in gene expression. The greater the absolute value of the abscissa, the greater the difference of expression between the two groups. The larger the ordinate value, the more significant the difference in expression. Genes with significant differences are represented by red and blue dots, and genes without significant differences are represented by green dots

Figure 2

Differential miRNA expression between COVID‐19 patients and healthy donors. Genes with significant differences are represented by red and blue dots, and genes without significant differences are represented by green dots

Figure 3

Differential gene expression between COVID‐19 patients and healthy donors. Each column represents a different sample. Lines represent different genes. The color represents the level of gene expression in the sample. Red indicates a high gene expression in the sample, and blue indicates a low gene expression in the sample

Figure 4

The GO classification of differentially expressed genes between the COVID‐19 patients and the control group

Figure 5

KEGG enrichment analysis of the differentially expressed genes