Construction of an autophagy interaction network based on competitive endogenous RNA reveals the key pathways and central genes of SARS-CoV-2 infection in vivo

Abstract

As of April 1, 2021, more than 2.8 million people have died of SARS-CoV-2 infection. In addition, the mutation of virus strains that have accompanied the pandemic has brought more severe challenges to pandemic control. Host microRNAs (miRNAs) are widely involved in a variety of biological processes of coronavirus infection, including autophagy in SARS-CoV-2 infection. However, the mechanisms underlying miRNAs involved in autophagy in SARS-CoV-2 infection have not been fully elucidated. In this study, the miRNA and messenger RNA (mRNA) expression profiles of patients with SARS-CoV-2 infection were investigated based on raw data from Gene Expression Omnibus (GEO) datasets, and potential novel biomarkers of autophagy were revealed by bioinformatics analyses. We identified 32 differentially expressed miRNAs and 332 differentially expressed mRNAs in patients with SARS-CoV-2 infection. Cytokine receptor related pathways were the most enriched pathways for differentially expressed miRNAs identified by pathway analysis. Most importantly, an autophagy interaction network, which was associated with the pathological processes of SARS-CoV-2 infection, especially with the cytokine storm, was constructed. In this network, hsa-miR-340–3p, hsa-miR-652–3p, hsa-miR-4772–5p, hsa-miR-192–5p, TP53INP2, and CCR2 may be biomarkers that predict changes in mild SARS-CoV-2 infection. Some molecules, including hsa-miR-1291 and CXCR4, were considered potential targets to predict the emergence of severe symptoms in SARS-CoV-2 infection. To our knowledge, this study provided the first profile analysis of an autophagy interaction network in SARS-CoV-2 infection and revealed several novel autophagy-related biomarkers for understanding the pathogenesis of SARS-CoV-2 infection in vivo.

Plasma miRNA profile at COVID-19 onset predicts severity status and mortality

“…We also observed up to 19 upregulated miRNAs in asymptomatic patients. Among the most upregulated miRNAs, hsa-miR-708-3p and hsa-miR-1291 were recently found by Chen et al as differentially expressed between patients with mild and severe symptoms of COVID-19 [ 36 ]. The hsa-miR-1291 was more than 14 times expressed in our asymptomatic patients.…”

“…This miRNA acts upstream of the chemokine receptor CCR2, which is known to induce monocyte and macrophage recruitment to sites of inflammation and regulates the immune response by controlling the proportion of effector and regulatory T cells [ 36 ]. An increased CCR2 expression has been reported in patients with severe COVID-19 [ 37 ], and similarly, hsa-miR-1291 has been pinpointed as a potential early biomarker of COVID-19 severity [ 36 ]. Therefore, tight control of inflammation by hsa-miR-1291 could be behind the COVID-19 control in asymptomatic patients.…”

Functional assessment of miR‑1291 in colon cancer cells

“…It has been reported that miR-1291 sensitizes cells to doxorubicin by suppressing multidrug resistance-associated protein 1 ( 35 ). Additionally, miR-1291 is considered to be a candidate biomarker for the diagnosis of acute myocardial infarction ( 36 ) and Bullous Pemphigoid ( 37 ), and is also a marker for the prediction of severe symptoms in SARS-CoV-2 infection ( 38 ). In relation to human cancers, miR-1291 has been reportedly upregulated in liver cirrhosis and hepatocellular carcinoma ( 39 ).…”

Friend or Foe? Implication of the autophagy-lysosome pathway in SARS-CoV-2 infection and COVID-19

“…Once entering the host cells, SARS-CoV-2 is expected to elicit wide ranges responses from the host machinery which would impact the viral replication. A recent study conducted a profiling analysis of miRNA and mRNA expression in patients with SARS-CoV-2 infection and found an extensive autophagy interaction network in cells infected with SARS-CoV-2 and revealed several novel autophagyrelated biomarkers [32]. Such analysis thus provides a valuable source of information to further dissect the effect of the autophagy-lysosome on SARS-CoV-2, and vice versa.…”