Construction and Investigation of Competing Endogenous RNA Networks and Candidate Genes Involved in SARS-CoV-2 Infection.

ABSTRACT

INTRODUCTION: The current COVID-19 pandemic caused by a novel coronavirus SARS-CoV-2 is a quickly developing global health crisis, yet the mechanisms of pathogenesis in COVID-19 are not fully understood. METHODS: The RNA sequencing data of SARS-CoV-2-infected cells was obtained from the Gene Expression Omnibus (GEO). The differentially expressed mRNAs (DEmRNAs), long non-coding RNAs (DElncRNAs), and microRNAs (DEmiRNAs) were identified by edgeR, and the SARS-CoV-2-associated competing endogenous RNA (ceRNA) network was constructed based on the prediction of bioinformatic databases. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted with the SARS-CoV-2-related DEmRNAs, and the protein-protein interaction network was also built basing on STRING database. The ROC analysis was performed for assessing the diagnostic efficiency of hub genes. RESULTS: The results indicated that SARS-CoV-2-related DEmRNAs were associated with the interferon signaling pathway and other antiviral processes, such as IFNL3, IFNL1 and CH25H. Our analysis suggested that lncRNA NEAT1 might regulate the host immune response through two miRNAs, hsa-miR-374-5p and hsa-miR-155-5p, which control the expression of SOCS1, IL6, IL1B, CSF1R, CD274, TLR6, and TNF. Additionally, IFI6, HRASLS2, IGFBP4 and PTN may be potential targets based on an analysis comparing the transcriptional responses of SARS-CoV-2 infection with that of other respiratory viruses. DISCUSSION: The unique ceRNA network identified potential non-coding RNAs and their possible targets as well as a new perspective to understand the molecular mechanisms of the host immune response to SARS-CoV-2. This study may also aid in the development of innovative diagnostic and therapeutic strategies.