Altered microRNA expression in severe COVID-19: potential prognostic and pathophysiological role
Abstract Background The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic is ongoing. The pathophysiology of SARS-CoV-2 infection is beginning to be elucidated but the role of microRNAs (miRNAs), small non-coding RNAs that regulate gene expression, remains incompletely understood. They play a role in the pathophysiology of viral infections with potential use as biomarkers. The objective of this study was to identify miRNAs as biomarkers of severe COVID-19 and to analyze their role in the pathophysiology of SARS-CoV-2 infection.Methods miRNA expression was measured in nasopharyngeal swabs from 20 patients with severe COVID-19, 21 patients with non-severe COVID-19 and 20 controls. Promising miRNAs to differentiate non-severe from severe COVID-19 patients were identified by differential expression analysis and sparse Partial Least Squares-Discriminant Analysis (sPLS-DA). ROC analysis, target prediction, GO enrichment and pathway analysis were used to analyze the role and the pertinence of these miRNAs in severe COVID-19.Results The number of expressed miRNAs was lower in severe COVID-19 patients compared to non-severe COVID-19 patients and controls. Among the differentially expressed miRNAs between severe COVID-19 and controls, 5 miRNAs were also differentially expressed between severe and non-severe COVID-19. sPLS-DA analysis highlighted 8 miRNAs, that allowed to discriminate the severe and non-severe COVID-19 cases. Target and functional analysis revealed enrichment for genes involved in viral infections and the cellular response to infection as well as one miRNA, hsa-miR-15b-5p, that targeted the SARS-CoV-2 RNA.The comparison of results of differential expression analysis and discriminant analysis revealed three miRNAs, namely hsa-miR-125a-5p, hsa-miR-491-5p and hsa-miR-200b-3p. These discriminated severe from non-severe cases with areas under the curve ranging from 0.76 to 0.80.Conclusions Our analysis of miRNA expression in nasopharyngeal swabs revealed several miRNAs of interest to discriminate severe and non-severe COVID-19. These miRNAs represent promising biomarkers and possibly targets for antiviral or anti-inflammatory treatment strategies..
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Preprint| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
bioRxiv.org - (2023) vom: 19. Nov. Zur Gesamtaufnahme - year:2023 |
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| Sprache: |
Englisch |
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| Beteiligte Personen: |
Garnier, Nathalie [VerfasserIn] |
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| Links: |
Volltext [kostenfrei] |
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| doi: |
10.1101/2022.03.21.22272480 |
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| PPN (Katalog-ID): |
XBI035567155 |
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| 520 | |a Abstract Background The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic is ongoing. The pathophysiology of SARS-CoV-2 infection is beginning to be elucidated but the role of microRNAs (miRNAs), small non-coding RNAs that regulate gene expression, remains incompletely understood. They play a role in the pathophysiology of viral infections with potential use as biomarkers. The objective of this study was to identify miRNAs as biomarkers of severe COVID-19 and to analyze their role in the pathophysiology of SARS-CoV-2 infection.Methods miRNA expression was measured in nasopharyngeal swabs from 20 patients with severe COVID-19, 21 patients with non-severe COVID-19 and 20 controls. Promising miRNAs to differentiate non-severe from severe COVID-19 patients were identified by differential expression analysis and sparse Partial Least Squares-Discriminant Analysis (sPLS-DA). ROC analysis, target prediction, GO enrichment and pathway analysis were used to analyze the role and the pertinence of these miRNAs in severe COVID-19.Results The number of expressed miRNAs was lower in severe COVID-19 patients compared to non-severe COVID-19 patients and controls. Among the differentially expressed miRNAs between severe COVID-19 and controls, 5 miRNAs were also differentially expressed between severe and non-severe COVID-19. sPLS-DA analysis highlighted 8 miRNAs, that allowed to discriminate the severe and non-severe COVID-19 cases. Target and functional analysis revealed enrichment for genes involved in viral infections and the cellular response to infection as well as one miRNA, hsa-miR-15b-5p, that targeted the SARS-CoV-2 RNA.The comparison of results of differential expression analysis and discriminant analysis revealed three miRNAs, namely hsa-miR-125a-5p, hsa-miR-491-5p and hsa-miR-200b-3p. These discriminated severe from non-severe cases with areas under the curve ranging from 0.76 to 0.80.Conclusions Our analysis of miRNA expression in nasopharyngeal swabs revealed several miRNAs of interest to discriminate severe and non-severe COVID-19. These miRNAs represent promising biomarkers and possibly targets for antiviral or anti-inflammatory treatment strategies. | ||
| 650 | 4 | |a Biology |7 (dpeaa)DE-84 | |
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| 700 | 1 | |a Pollet, Kato |4 aut | |
| 700 | 1 | |a Fourcot, Marie |4 aut | |
| 700 | 1 | |a Caplan, Morgan |4 aut | |
| 700 | 1 | |a Marot, Guillemette |4 aut | |
| 700 | 1 | |a Goutay, Julien |4 aut | |
| 700 | 1 | |a Labreuche, Julien |4 aut | |
| 700 | 1 | |a Soncin, Fabrice |4 aut | |
| 700 | 1 | |a Boukherroub, Rabah |4 aut | |
| 700 | 1 | |a Hober, Didier |4 aut | |
| 700 | 1 | |a Szunerits, Sabine |4 aut | |
| 700 | 1 | |a Poissy, Julien |4 aut | |
| 700 | 1 | |a Engelmann, Ilka |4 aut | |
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