microRNA 1307 Is a Potential Target for SARS-CoV-2 Infection: An in Vitro Model

Elif Damla Arisan; D Alwyn Dart; Guy H Grant; Andrew Dalby; Derya Dilek Kancagi; Raife Dilek Turan; Bulut Yurtsever; Gozde Sir Karakus; Ercument Ovali; Sigrun Lange; Pinar Uysal-Onganer

doi:10.1021/acsomega.2c05245

microRNA 1307 Is a Potential Target for SARS-CoV-2 Infection: An in Vitro Model

ACS Omega. 2022 Oct 11;7(42):38003-38014. doi: 10.1021/acsomega.2c05245. eCollection 2022 Oct 25.

Authors

Affiliations

¹ Gebze Technical University, Institute of Biotechnology, Gebze, Kocaeli 41400, Turkiye.
² Institute of Medical and Biomedical Education, St George's University of London, Cranmer Terrace, Tooting, London SW17 0RE, United Kingdom.
³ School of Life Sciences, University of Bedfordshire, Park Square, Luton LU1 3JU, United Kingdom.
⁴ School of Life Sciences, University of Westminster, London W1W 6UW, United Kingdom.
⁵ Acibadem Labcell Cellular Therapy Laboratory, İstanbul 34457, Turkiye.
⁶ Yeditepe University, Institute of Biotechnology, İstanbul 34755, Turkiye.
⁷ Tissue Architecture and Regeneration Research Group, School of Life Sciences, University of Westminster, London W1W 6UW, United Kingdom.
⁸ Cancer Research Group, School of Life Sciences, University of Westminster, London W1W 6UW, United Kingdom.

Abstract

microRNAs (miRs) are proposed as critical molecular targets in SARS-CoV-2 infection. Our recent in silico studies identified seven SARS-CoV-2 specific miR-like sequences, which are highly conserved with humans, including miR-1307-3p, with critical roles in COVID-19. In this current study, Vero cells were infected with SARS-CoV-2, and miR expression profiles were thereafter confirmed by qRT-PCR. miR-1307-3p was the most highly expressed miR in the infected cells; we, therefore, transiently inhibited its expression in both infected and uninfected cells. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) cell proliferation assay assessed cell viability following SARS-CoV-2 infection, identifying that miR-1307 expression is inversely correlated with cell viability. Lastly, changes in miR-1307-dependent pathways were analyzed through a detailed miRNOME and associated in silico analysis. In addition to our previously identified miRs, including miR-1307-3p, the upregulation of miR-193a-5p, miR-5100, and miR-23a-5p and downregulation of miR-130b-5p, miR34a-5p, miR-505-3p, miR181a-2-3p, miR-1271-5p, miR-598-3p, miR-34c-3p, and miR-129-5p were also established in Vero cells related to general lung disease-related genes following SARS-CoV-2 infection. Targeted anti-miR-1307-3p treatment rescued cell viability in infection when compared to SARS CoV-2 mediated cell cytotoxicity only. We furthermore identified by in silico analysis that miR-1307-3p is conserved in all SARS-CoV-2 sequences/strains, except in the BA.2 variant, possibly contributing to the lower disease severity of this variant, which warrants further investigation. Small RNA seq analysis was next used to evaluate alterations in the miRNOME, following miR-1307-3p manipulation, identifying critical pathobiological pathways linked to SARS-CoV-2 infection-mediated upregulation of this miR. On the basis of our findings, miRNAs like miR-1307-3p play a critical role in SARS-CoV-2 infection, including via effects on disease progression and severity.