Gajate-Arenas Malena, Sirvent-Blanco Candela, García-Pérez Omar, Domínguez-de-Barros Angélica, Piñero José E, Lorenzo-Morales Jacob, Córdoba-Lanús Elizabeth
Instituto Universitario de Enfermedades Tropicales y Salud Pública de Canarias (IUETSPC), Universidad de La Laguna, La Laguna, Tenerife, 38029, Spain.
Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, 28029, Spain.
Mol Med. 2025 Mar 15;31(1):102. doi: 10.1186/s10020-025-01154-0.
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.
微小RNA（miRNA）是细胞稳态所必需的基因调节因子，其改变与病理状态相关，包括像2019冠状病毒病（COVID-19）这样的传染病。识别轻度COVID-19中循环miRNA的改变谱可能会增强我们对严重急性呼吸综合征冠状病毒2（SARS-CoV-2）发病机制和临床表型范围的认识。在本研究中，通过下一代测序（NGS）进行了miRNA筛选，并通过逆转录定量聚合酶链反应（RT-qPCR）在40例轻症患者的血清中验证了13种所得miRNA的表达水平，并与29名未感染个体进行了比较。进行了计算机分析以检测靶基因及其相关途径。在经验证的miRNA中，发现感染个体中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）和miR-210-3p（p = 0.002）表达下调。只有miR-27a-5p在COVID-19患者中过表达（p = 0.013），并与SARS-CoV-2感染相关（p = 0.010）。京都基因与基因组百科全书（KEGG）途径和基因本体（GO）分析表明，差异表达的miRNA与病毒过程或免疫途径相关：miR-27a-5p作用于转化生长因子-β（TGF-β）途径；miR-21-5p靶向与肺部炎症反应相关的SMAD7；miR-1246作用于p53途径；miR-4508作用于细胞间黏附分子2（ICAM2）。总之，最相关的miRNA，即miR-27a-5p和miR-21-5p，在轻度COVID-19中表达不同。在轻度COVID-19病例中观察到的miR-27a-5p较高表达可能提示对该疾病严重形式具有保护作用。miR-21-5p表达降低可能预防肺部炎症和纤维化进展。轻度COVID-19病例中miR-1246和miR-4508的下调可能有助于对感染进行正确控制。此外，miR-423-5p可能是SARS-CoV-2感染早期阶段合适的生物标志物。
