新型冠状病毒肺炎患者循环 ACE2 网络相关 microRNAs 的变化。

Alteration of circulating ACE2-network related microRNAs in patients with COVID-19.

机构信息

Department of Experimental and Clinical Pharmacology, Center for Preclinical Research and Technology CEPT, Medical University of Warsaw, 02-097, Warsaw, Poland.

Department of Neurochemistry, Institute of Psychiatry and Neurology, Sobieskiego 9 Street, 02-957, Warsaw, Poland.

出版信息

Sci Rep. 2024 Jun 12;14(1):13573. doi: 10.1038/s41598-024-58037-3.

DOI:10.1038/s41598-024-58037-3

PMID:38866792

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11169442/

Abstract

Angiotensin converting enzyme 2 (ACE2) serves as the primary receptor for the SARS-CoV-2 virus and has implications for the functioning of the cardiovascular system. Based on our previously published bioinformatic analysis, in this study we aimed to analyze the diagnostic and predictive utility of miRNAs (miR-10b-5p, miR-124-3p, miR-200b-3p, miR-26b-5p, miR-302c-5p) identified as top regulators of ACE2 network with potential to affect cardiomyocytes and cardiovascular system in patients with COVID-19. The expression of miRNAs was determined through qRT-PCR in a cohort of 79 hospitalized COVID-19 patients as well as 32 healthy volunteers. Blood samples and clinical data of COVID-19 patients were collected at admission, 7-days and 21-days after admission. We also performed SHAP analysis of clinical data and miRNAs target predictions and advanced enrichment analyses. Low expression of miR-200b-3p at the seventh day of admission is indicative of predictive value in determining the length of hospital stay and/or the likelihood of mortality, as shown in ROC curve analysis with an AUC of 0.730 and a p-value of 0.002. MiR-26b-5p expression levels in COVID-19 patients were lower at the baseline, 7 and 21-days of admission compared to the healthy controls (P < 0.0001). Similarly, miR-10b-5p expression levels were lower at the baseline and 21-days post admission (P = 0.001). The opposite situation was observed in miR-124-3p and miR-302c-5p. Enrichment analysis showed influence of analyzed miRNAs on IL-2 signaling pathway and multiple cardiovascular diseases through COVID-19-related targets. Moreover, the COVID-19-related genes regulated by miR-200b-3p were linked to T cell protein tyrosine phosphatase and the HIF-1 transcriptional activity in hypoxia. Analysis focused on COVID-19 associated genes showed that all analyzed miRNAs are strongly affecting disease pathways related to CVDs which could be explained by their strong interaction with the ACE2 network.

摘要

血管紧张素转换酶 2（ACE2）是 SARS-CoV-2 病毒的主要受体，对心血管系统的功能有影响。基于我们之前发表的生物信息学分析，在这项研究中，我们旨在分析被鉴定为 ACE2 网络的顶级调节剂的 miRNAs（miR-10b-5p、miR-124-3p、miR-200b-3p、miR-26b-5p、miR-302c-5p）的诊断和预测效用，这些 miRNAs 有可能影响 COVID-19 患者的心肌细胞和心血管系统。通过 qRT-PCR 在 79 名住院 COVID-19 患者和 32 名健康志愿者的队列中确定了 miRNA 的表达。COVID-19 患者的血液样本和临床数据在入院时、入院后 7 天和 21 天收集。我们还对临床数据和 miRNAs 靶标预测进行了 SHAP 分析，并进行了高级富集分析。在入院后第 7 天 miR-200b-3p 的低表达表明在确定住院时间和/或死亡率方面具有预测价值，ROC 曲线分析的 AUC 为 0.730，p 值为 0.002。与健康对照组相比，COVID-19 患者在入院时、7 天和 21 天的 miR-26b-5p 表达水平较低（P<0.0001）。同样，miR-10b-5p 的表达水平在入院后基线和 21 天也较低（P=0.001）。而 miR-124-3p 和 miR-302c-5p 的情况则相反。富集分析表明，分析的 miRNAs 通过与 COVID-19 相关的靶标影响 IL-2 信号通路和多种心血管疾病。此外，miR-200b-3p 调节的 COVID-19 相关基因与 T 细胞蛋白酪氨酸磷酸酶和缺氧时的 HIF-1 转录活性有关。针对 COVID-19 相关基因的分析表明，所有分析的 miRNAs 都强烈影响与 CVD 相关的疾病途径，这可以解释它们与 ACE2 网络的强烈相互作用。