miR-27a-5p, miR-21-5p, miR-1246 and miR-4508: a candidate microRNA signature in the protection and regulation of viral infection in mild COVID-19

Abstract MicroRNAs (miRNAs) are gene regulators essential for cell homeostasis, their alteration is related to a pathological state, including infectious diseases like COVID-19. Identifying an altered profile of circulating miRNAs in mild COVID-19 may enhance our knowledge of the pathogenesis of SAR...

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Main Authors: Malena Gajate-Arenas, Candela Sirvent-Blanco, Omar García-Pérez, Angélica Domínguez-de-Barros, José E. Piñero, Jacob Lorenzo-Morales, Elizabeth Córdoba-Lanús
Format: Article
Language:English
Published: BMC 2025-03-01
Series:Molecular Medicine
Online Access:https://doi.org/10.1186/s10020-025-01154-0
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author Malena Gajate-Arenas
Candela Sirvent-Blanco
Omar García-Pérez
Angélica Domínguez-de-Barros
José E. Piñero
Jacob Lorenzo-Morales
Elizabeth Córdoba-Lanús
author_facet Malena Gajate-Arenas
Candela Sirvent-Blanco
Omar García-Pérez
Angélica Domínguez-de-Barros
José E. Piñero
Jacob Lorenzo-Morales
Elizabeth Córdoba-Lanús
author_sort Malena Gajate-Arenas
collection DOAJ
description Abstract MicroRNAs (miRNAs) are gene regulators essential for cell homeostasis, their alteration is related to a pathological state, including infectious diseases like COVID-19. Identifying an altered profile of circulating miRNAs in mild COVID-19 may enhance our knowledge of the pathogenesis of SARS-CoV-2 and the range of clinical phenotypes. In the present study, a miRNA screening was performed by Next Generation Sequencing (NGS), and the expression levels of 13 resulting miRNAs were validated through RT-qPCR in the serum of 40 mild cases compared to 29 non-infected individuals. An in-silico analysis was performed to detect target genes and their related pathways. From the validated miRNAs, miR-1246 (p < 0.001), miR-423-5p (p < 0.001), miR-21-5p (p = 0.005), miR-146a-5p (p < 0.001), miR-4508 (p = 0.001), miR-629-5p (p < 0.001), and miR-210-3p (p = 0.002) were found downregulated in infected individuals. Only miR-27a-5p was overexpressed in subjects with COVID-19 (p = 0.013) and associated with SARS-CoV-2 infection (p = 0.010). The KEGG pathways and GO analysis revealed that the differentially expressed miRNAs were related to viral processes or immunological pathways: miR-27a-5p acts on the TGF-beta pathway; miR-21-5p targets SMAD7, which is associated with the inflammatory response in the lung; miR-1246 acts on p53 pathway; and miR-4508 acts on ICAM2. In conclusion, the most relevant miRNAs, miR-27a-5p and miR-21-5p, were differently expressed in mild forms of COVID-19. The higher expression of miR-27a-5p observed in mild COVID-19 cases may suggest a protective effect against severe forms of the disease. Reduced expression of miR-21-5p may prevent pulmonary inflammation and the progression of fibrosis. The downregulation of miR-1246 and miR-4508 in mild COVID-19 cases may conduct the correct control of the infection. Moreover, miR-423-5p might be a suitable biomarker in the early stages of SARS-CoV-2 infection.
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spelling doaj-art-73b96c8ef9b84bdd992f82dc9844812a2025-08-20T03:02:21ZengBMCMolecular Medicine1528-36582025-03-0131111010.1186/s10020-025-01154-0miR-27a-5p, miR-21-5p, miR-1246 and miR-4508: a candidate microRNA signature in the protection and regulation of viral infection in mild COVID-19Malena Gajate-Arenas0Candela Sirvent-Blanco1Omar García-Pérez2Angélica Domínguez-de-Barros3José E. Piñero4Jacob Lorenzo-Morales5Elizabeth Córdoba-Lanús6Instituto Universitario de Enfermedades Tropicales y Salud Pública de Canarias (IUETSPC), Universidad de La LagunaInstituto Universitario de Enfermedades Tropicales y Salud Pública de Canarias (IUETSPC), Universidad de La LagunaInstituto Universitario de Enfermedades Tropicales y Salud Pública de Canarias (IUETSPC), Universidad de La LagunaInstituto Universitario de Enfermedades Tropicales y Salud Pública de Canarias (IUETSPC), Universidad de La LagunaInstituto Universitario de Enfermedades Tropicales y Salud Pública de Canarias (IUETSPC), Universidad de La LagunaInstituto Universitario de Enfermedades Tropicales y Salud Pública de Canarias (IUETSPC), Universidad de La LagunaInstituto Universitario de Enfermedades Tropicales y Salud Pública de Canarias (IUETSPC), Universidad de La LagunaAbstract MicroRNAs (miRNAs) are gene regulators essential for cell homeostasis, their alteration is related to a pathological state, including infectious diseases like COVID-19. Identifying an altered profile of circulating miRNAs in mild COVID-19 may enhance our knowledge of the pathogenesis of SARS-CoV-2 and the range of clinical phenotypes. In the present study, a miRNA screening was performed by Next Generation Sequencing (NGS), and the expression levels of 13 resulting miRNAs were validated through RT-qPCR in the serum of 40 mild cases compared to 29 non-infected individuals. An in-silico analysis was performed to detect target genes and their related pathways. From the validated miRNAs, miR-1246 (p < 0.001), miR-423-5p (p < 0.001), miR-21-5p (p = 0.005), miR-146a-5p (p < 0.001), miR-4508 (p = 0.001), miR-629-5p (p < 0.001), and miR-210-3p (p = 0.002) were found downregulated in infected individuals. Only miR-27a-5p was overexpressed in subjects with COVID-19 (p = 0.013) and associated with SARS-CoV-2 infection (p = 0.010). The KEGG pathways and GO analysis revealed that the differentially expressed miRNAs were related to viral processes or immunological pathways: miR-27a-5p acts on the TGF-beta pathway; miR-21-5p targets SMAD7, which is associated with the inflammatory response in the lung; miR-1246 acts on p53 pathway; and miR-4508 acts on ICAM2. In conclusion, the most relevant miRNAs, miR-27a-5p and miR-21-5p, were differently expressed in mild forms of COVID-19. The higher expression of miR-27a-5p observed in mild COVID-19 cases may suggest a protective effect against severe forms of the disease. Reduced expression of miR-21-5p may prevent pulmonary inflammation and the progression of fibrosis. The downregulation of miR-1246 and miR-4508 in mild COVID-19 cases may conduct the correct control of the infection. Moreover, miR-423-5p might be a suitable biomarker in the early stages of SARS-CoV-2 infection.https://doi.org/10.1186/s10020-025-01154-0
spellingShingle Malena Gajate-Arenas
Candela Sirvent-Blanco
Omar García-Pérez
Angélica Domínguez-de-Barros
José E. Piñero
Jacob Lorenzo-Morales
Elizabeth Córdoba-Lanús
miR-27a-5p, miR-21-5p, miR-1246 and miR-4508: a candidate microRNA signature in the protection and regulation of viral infection in mild COVID-19
Molecular Medicine
title miR-27a-5p, miR-21-5p, miR-1246 and miR-4508: a candidate microRNA signature in the protection and regulation of viral infection in mild COVID-19
title_full miR-27a-5p, miR-21-5p, miR-1246 and miR-4508: a candidate microRNA signature in the protection and regulation of viral infection in mild COVID-19
title_fullStr miR-27a-5p, miR-21-5p, miR-1246 and miR-4508: a candidate microRNA signature in the protection and regulation of viral infection in mild COVID-19
title_full_unstemmed miR-27a-5p, miR-21-5p, miR-1246 and miR-4508: a candidate microRNA signature in the protection and regulation of viral infection in mild COVID-19
title_short miR-27a-5p, miR-21-5p, miR-1246 and miR-4508: a candidate microRNA signature in the protection and regulation of viral infection in mild COVID-19
title_sort mir 27a 5p mir 21 5p mir 1246 and mir 4508 a candidate microrna signature in the protection and regulation of viral infection in mild covid 19
url https://doi.org/10.1186/s10020-025-01154-0
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