ABSTRACT The role for circulating miRNAs as biomarkers of the COVID-19 disease remains uncertain. We analysed the circulating miRNA profile in twelve COVID-19 patients with moderate-severe disease. This analysis was conducted by performing next generation sequencing (NGS) followed by real-time polymerase chain reaction (RT-qPCR). Compared with healthy controls, we detected significant changes in the circulating miRNA profile of COVID-19 patients. The miRNAs that were significantly altered in all the COVID-19 patients were miR-150-5p, miR-375, miR-122-5p, miR-494-3p, miR-3197, miR-4690-5p, miR-1915-3p, and miR-3652. Infection assays performed using miRNA mimics in HEK-293 T cells determined miR-150-5p to have a crucial role in SARS-CoV-2 infection and this was based on the following data: (i) miR-150-5p mimic lowered in vitro SARS-CoV-2 infection; (ii) miR-150-5p inhibitor reversed the effects of miR-150-5p mimic on SARS-CoV-2 infection of cells; and (iii) a novel miRNA recognition element (MRE) was identified in the coding strand of SARS-CoV-2 nsp10 , the expression of which could be inhibited by miR-150-5p mimic. Our findings identified crucial miRNA footprints in COVID-19 patients with moderate-severe disease. A combination of co-transfection and Western blotting experiments also determined the ability of miR-150-5p to inhibit SARS-CoV-2 infection via directly interacting with MRE in the coding strand of nsp10 . Our investigation showed that a sharp decline in the miR-150-5p plasma levels in COVID-19 patients may support enhanced SARS-CoV-2 infection. Furthermore, this study provides insight into one possible mechanism by which COVID-19-induced changes to miR-150-5p levels may promote SARS-CoV-2 infection via modulating nsp10 expression.
【저자키워드】 COVID-19, SARS-CoV-2, nsp10, plasma, miR-150-5p, circulating biomarkers, 【초록키워드】 Biomarker, Biomarkers, T cells, SARS-COV-2 infection, Sequencing, NGS, miRNA, Infection, in vitro, COVID-19 disease, polymerase chain reaction, RT-qPCR, miRNAs, nsp10, real-time polymerase chain reaction, experiment, inhibitor, disease, expression, change, mechanism, COVID-19 patients, Combination, Analysis, Plasma levels, COVID-19 patient, followed by, Chain Reaction, Support, healthy controls, circulating, circulating miRNAs, western blotting, transfection, infection assays, co-transfection, coding strand, miR-150, miR-375, Effect, Cell, polymerase chain, significant changes in, performed, significantly, inhibited, conducted, analysed, provide, promote, reversed, circulating miRNA, inhibit SARS-CoV-2, miRNA profile, moderate-severe, modulating, remains uncertain, 【제목키워드】 Infection, biology of SARS-CoV-2,