In silico identification of potential miRNAs -mRNA inflammatory networks implicated in the pathogenesis of COVID-19

Abstract

COVID-19 has been found to affect the expression profile of several mRNAs and miRNAs, leading to dysregulation of a number of signaling pathways, particularly those related to inflammatory responses. In the current study, a systematic biology procedure was used for the analysis of high-throughput expression data from blood specimens of COVID-19 and healthy individuals. Differentially expressed miRNAs in blood specimens of COVID-19 vs. healthy specimens were then identified to construct and analyze miRNA-mRNA networks and predict key miRNAs and genes in inflammatory pathways. Our results showed that 171 miRNAs were expressed as outliers in box plot and located in the critical areas according to our statistical analysis. Among them, 8 miRNAs, namely miR-1275, miR-4429, miR-4489, miR-6721-5p, miR-5010-5p, miR-7110-5p, miR-6804-5p and miR-6881-3p were found to affect expression of key genes in NF-KB, JAK/STAT and MAPK signaling pathways implicated in COVID-19 pathogenesis. In addition, our results predicted that 25 genes involved in above-mentioned inflammatory pathways were targeted not only by these 8 miRNAs but also by other obtained miRNAs (163 miRNAs). The results of the current in silico study represent candidate targets for further studies in COVID-19.

Keywords: COVID-19; Inflammation; JAK-STAT; MAPK; MicroRNA (miRNA); NF-κB.

Fig. 1

Study design flowchart.

Fig. 2

Short description of obtained results in this study.

Fig. 3

A) Frequency distribution of miRNAs involved in COVID-19 pathogenesis. X-axis shows the miRNA expression profiling intervals based on fold changes reported for miRNA expression in high-throughput studies. Y-axis shows the frequency of miRNAs in determined intervals B) Frequency distribution of categorical miRNAs involved in COVID-19 pathogenesis. X-axis shows the miRNA expression profiling intervals based on fold changes reported for miRNA expression in high-throughput studies. Y-axis shows the frequency of miRNAs in determined intervals. Y-axis shows the frequency of miRNAs in determined intervals (0–400) C) Box-Plot with test of miRNAs involved in COVID-19 pathogenesis. miRNA expression profiling values (From bottom to top of the chart: Minimum, Quartile 1, Median, Quartile 3, Maximum).

Fig. 4

The potential interactions between potential target genes of miRNAs of interest in NF-KB, JAK/STAT and MAPK signaling pathways participating in COVID-19 pathogenesis and miR-1275, miR-4429, miR-4489, miR-6721-5p, miR-5010-5p, miR-7110-5p, miR-6804-5p and miR-6881–3p were depicted by Cytoscape. Genes that have more interactions are indicated larger in size. Moreover, there is direct relation between the number of protein interactions and color intensity.

Fig. 5

Predicted interactions between target genes of miRNAs of interest in other signaling pathways involved in COVID-19 pathogenesis and miR-1275, miR-4429, miR-4489, miR-6721-5p, miR-5010-5p, miR-7110-5p, miR-6804-5p and miR-6881–3p were depicted via Cytoscape. There is direct relation between the number of protein interactions and color intensity.

Fig. 6

The role of miRNAs of interest (miR-1275, miR-4429, miR-4489, miR-6721-5p, miR-5010-5p, miR-7110-5p, miR-6804-5p and miR-6881–3p) in regulating key genes in NF-KB and MAPK signaling pathways contributing to COVID-19 pathogenesis.

Fig. 7

The role of miRNAs of interest (miR-1275, miR-4429, miR-4489, miR-6721-5p, miR-5010-5p, miR-7110-5p, miR-6804-5p and miR-6881–3p) in regulating key genes in JAK/STAT signaling pathway involved in COVID-19 pathogenesis.

Fig. 8

Potential interactions between target genes of miRNAs of interest in other signaling pathways involved in COVID-19 pathogenesis and miR-1275, miR-4429, miR-4489, miR-6721-5p, miR-5010-5p, miR-7110-5p, miR-6804-5p and miR-6881–3p were depicted via Cytoscape. There is direct relation between the number of protein interactions and color intensity.