Interplay between SARS-CoV-2-derived miRNAs, immune system, vitamin D pathway and respiratory system

J Cell Mol Med. 2021 Aug;25(16):7825-7839. doi: 10.1111/jcmm.16694. Epub 2021 Jun 22.

Abstract

The new coronavirus pandemic started in China in 2019. The intensity of the disease can range from mild to severe, leading to death in many cases. Despite extensive research in this area, the exact molecular nature of virus is not fully recognized; however, according to pieces of evidence, one of the mechanisms of virus pathogenesis is through the function of viral miRNAs. So, we hypothesized that SARS-CoV-2 pathogenesis may be due to targeting important genes in the host with its miRNAs, which involved in the respiratory system, immune pathways and vitamin D pathways, thus possibly contributing to disease progression and virus survival. Potential miRNA precursors and mature miRNA were predicted and confirmed based on the virus genome. The next step was to predict and identify their target genes and perform functional enrichment analysis to recognize the biological processes connected with these genes in the three pathways mentioned above through several comprehensive databases. Finally, cis-acting regulatory elements in 5' regulatory regions were analysed, and the analysis of available RNAseq data determined the expression level of genes. We revealed that thirty-nine mature miRNAs could theoretically derive from the SARS-CoV-2 genome. Functional enrichment analysis elucidated three highlighted pathways involved in SARS-CoV-2 pathogenesis: vitamin D, immune system and respiratory system. Our finding highlighted genes' involvement in three crucial molecular pathways and may help develop new therapeutic targets related to SARS-CoV-2.

Keywords: SARS-COV2; bioinformatics; immune system; miRNA; respiratory system; vitamin D pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • COVID-19 / genetics
  • COVID-19 / immunology*
  • COVID-19 / virology
  • Gene Expression Regulation
  • Host-Pathogen Interactions / physiology*
  • Humans
  • Immune System / virology
  • MicroRNAs*
  • Molecular Sequence Annotation
  • Promoter Regions, Genetic
  • RNA, Viral
  • Respiratory System / virology
  • SARS-CoV-2 / genetics*
  • SARS-CoV-2 / pathogenicity
  • Vitamin D / metabolism*

Substances

  • MicroRNAs
  • RNA, Viral
  • Vitamin D