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血浆微小RNA与COVID-19严重程度及预后的关联。

Association of plasma microRNAs with COVID-19 severity and outcome.

作者信息

Salem Sohair, Lotfy Randa, Eltaweel Noha, Elbadry Mohamed

机构信息

Molecular Genetics & Enzymology Department, Human Genetics and Genome Research Institute, National Research Centre, Cairo, Egypt.

Molecular Genetics & Enzymology Department, Human Genetics and Genome Research Institute, National Research Centre, Cairo, Egypt.

出版信息

J Genet Eng Biotechnol. 2024 Dec;22(4):100433. doi: 10.1016/j.jgeb.2024.100433. Epub 2024 Nov 14.

Abstract

OBJECTIVE

As one of the remarkable host responses to SARS-CoV-2 infection, circulating microRNAs (miRNAs) represent important diagnostic and prognostic diseases biomarkers. The study is a step towards highlighting the role of miRNAs in COVID-19 pathogenesis and severity.

METHODS

In this case-control study, miRCURY LNA miRNA PCR plasma panel (168 miRNAs) was applied and the expression of the altered miRNAs was then analysed by quantitative real time PCR for 120 COVID-19 patients (30 mild, 30 moderate, 30 severe, and 30 critical) and 30 healthy subjects.

RESULTS

The initial screening showed that 30 miRNAs displayed altered expression, out of them, only eleven miRNAs (miR-885-5p, miR-141-3p, miR-21-5p, miR-127-3p, miR-99b-5p, let-7d-3p, miR-375, miR-1260a, miR-139-5p, miR-28-5p and miR-34a-5p) were dysregulated in the plasma of COVID-19 patients; all of them were significantly overexpressed. By applying ROC curve analysis, AUC for the eleven miRNAs were ranged from 0.65 to 0.83, and the AUC for the combined miRNAs was 0.93. Ten miRNAs (miR-141-3p, miR-181a-5p, miR-221-3p, miR-223-5p, miR99b-5p, Let-7d-3p, miR-375, miR-199a-5p, miR-139-5p and miR-28-5p) exhibited a significant change in their expression between different severity groups. Patients with positive outcome were found to have increased miR-375 and decreased miR-99b-5p expression levels. Bioinformatic prediction showed that, out of the eleven dysregulated miRNAs, five miRNAs (miR-139-5p, -34a-5p, -28-5p, -21-5p and -885-5p) have the ability to regulate at least two genes related to COVID-19 according to KEGG database.

CONCLUSION

miRNAs are dysregulated in COVID-19 patients and associated with severity degree and patients' outcome.

摘要

目的

作为对严重急性呼吸综合征冠状病毒2(SARS-CoV-2)感染的显著宿主反应之一,循环微小RNA(miRNA)是重要的疾病诊断和预后生物标志物。本研究旨在突出miRNA在2019冠状病毒病(COVID-19)发病机制和严重程度中的作用。

方法

在这项病例对照研究中,应用miRCURY LNA miRNA PCR血浆检测板(检测168种miRNA),然后通过定量实时PCR分析120例COVID-19患者(30例轻症、30例中症、30例重症和30例危重症)和30名健康受试者中miRNA表达的变化。

结果

初步筛选显示30种miRNA表达改变,其中只有11种miRNA(miR-885-5p、miR-141-3p、miR-21-5p、miR-127-3p、miR-99b-5p、let-7d-3p、miR-375、miR-1260a、miR-139-5p、miR-28-5p和miR-34a-5p)在COVID-19患者血浆中表达失调;所有这些miRNA均显著过表达。通过应用ROC曲线分析,11种miRNA的曲线下面积(AUC)在0.65至0.83之间,联合miRNA的AUC为0.93。10种miRNA(miR-141-3p、miR-181a-5p、miR-221-3p、miR-223-5p、miR99b-5p、Let-7d-3p、miR-375、miR-199a-5p、miR-139-5p和miR-28-5p)在不同严重程度组之间的表达有显著变化。发现预后良好的患者miR-375表达增加,miR-99b-5p表达水平降低。生物信息学预测显示,在11种失调的miRNA中,根据京都基因与基因组百科全书(KEGG)数据库,5种miRNA(miR-139-5p、-34a-5p、-28-5p、-21-5p和-885-5p)能够调节至少两个与COVID-19相关的基因。

结论

COVID-19患者中miRNA表达失调,且与疾病严重程度和患者预后相关。

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