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Mol Med . 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

tetano

Editor, Senior Moderator
Mol Med


. 2025 Mar 15;31(1):102.
doi: 10.1186/s10020-025-01154-0. 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

Malena Gajate-Arenas[SUP] #[/SUP][SUP] 1 2 [/SUP], Candela Sirvent-Blanco[SUP] #[/SUP][SUP] 1 [/SUP], Omar García-Pérez[SUP] 1 2 [/SUP], Angélica Domínguez-de-Barros[SUP] 1 2 [/SUP], José E Piñero[SUP] 1 2 3 [/SUP], Jacob Lorenzo-Morales[SUP] 4 5 6 [/SUP], Elizabeth Córdoba-Lanús[SUP] 7 8 [/SUP]



Affiliations
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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