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. (September 2021)

• Record Type: Journal Article
• Authors: Chen, Zhihao; Wang, Xi; Li, Liubing; Han, Mingxiao; Wang, Min; Li, Ziyuan; Xie, Xiaolu; Du, Hong; Xie, Zonggang; Zhang, Haifang
• Is Part Of: Microbial pathogenesis. Volume 158(2021)
• Publication Date: 2021-09
• Subjects: miRNAs -- mRNAs -- Autophagy -- SARS-CoV-2 -- COVID-19; Pathogenic microorganisms -- Periodicals; Pathology, Molecular -- Periodicals; Communicable Diseases -- microbiology -- Periodicals; Communicable Diseases -- parasitology -- Periodicals; Micro-organismes pathogènes -- Périodiques; Pathologie moléculaire -- Périodiques; Electronic journals; 616.9041
• DOI: 10.1016/j.micpath.2021.105051
• Languages: English
• ISSNs: 0882-4010

Abstract

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. Highlights: The first autophagy interaction network associated with the SARS-CoV-2 infection was constructed and verified by the analysis of COVID-19 patients and healthy individuals. Several potential novel biomarkers were revealed for understanding the pathogenesis of SARS-CoV-2 infections in vivo. This study supported previous studies that suggested BCL2L1, CCR2, CXCR4, hsa-miR-34c-5p, and hsa-miR-27a-3p as important factors and promising biomarkers in SARS-CoV-2 infection. This study showed that the autophagy interaction network we constructed participates extensively in the cytokine storm of SARS-CoV-2 infection. The clinical characteristics of autophagy-related genes has been verified, and these target genes could be a focus in the current pandemic.