miR-1207-5p Can Contribute to Dysregulation of Inflammatory Response in COVID-19 via Targeting SARS-CoV-2 RNA

Abstract

The present study focuses on the role of human miRNAs in SARS-CoV-2 infection. An extensive analysis of human miRNA binding sites on the viral genome led to the identification of miR-1207-5p as potential regulator of the viral Spike protein. It is known that exogenous RNA can compete for miRNA targets of endogenous mRNAs leading to their overexpression. Our results suggest that SARS-CoV-2 virus can act as an exogenous competing RNA, facilitating the over-expression of its endogenous targets. Transcriptomic analysis of human alveolar and bronchial epithelial cells confirmed that the CSF1 gene, a known target of miR-1207-5p, is over-expressed following SARS-CoV-2 infection. CSF1 enhances macrophage recruitment and activation and its overexpression may contribute to the acute inflammatory response observed in severe COVID-19. In summary, our results indicate that dysregulation of miR-1207-5p-target genes during SARS-CoV-2 infection may contribute to uncontrolled inflammation in most severe COVID-19 cases.

Keywords: SARS-CoV-2; competing RNAs; inflammatory response; macrophage recruitment; miRNA target prediction; microRNA regulatory network.