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长链非编码 RNA-GAS5/miRNA-200/ACE2 分子通路对 COVID-19 严重程度的影响。

The Impact of lncRNA-GAS5/miRNA-200/ACE2 Molecular Pathway on the Severity of COVID-19.

机构信息

Medical Biochemistry and Molecular Biology Department, Faculty of Medicine, Cairo University, Cairo, Egypt.

Biochemistry Department, Faculty of Pharmacy, Ahram Canadian University, 6th of October City, Egypt.

出版信息

Curr Med Chem. 2024;31(9):1142-1151. doi: 10.2174/0929867330666230515144133.

DOI:10.2174/0929867330666230515144133
PMID:37190816
Abstract

BACKGROUND

The severe acute respiratory syndrome coronavirus 2 (SARSCoV- 2), which is responsible for coronavirus disease (COVID-19), potentially has severe adverse effects, leading to public health crises worldwide. In COVID-19, deficiency of ACE-2 is linked to increased inflammation and cytokine storms via increased angiotensin II levels and decreased ACE-2/Mas receptor axis activity. MiRNAs are small sequences of noncoding RNAs that regulate gene expression by binding to the targeted mRNAs. MiR-200 dysfunction has been linked to the development of ARDS following acute lung injury and has been proposed as a key regulator of ACE2 expression. LncRNA growth arrest-specific transcript 5 (GAS5) has been recently studied for its modulatory effect on the miRNA-200/ACE2 axis.

OBJECTIVE

The current study aims to investigate the role of lncRNA GAS5, miRNA-200, and ACE2 as new COVID-19 diagnostic markers capable of predicting the severity of SARS-CoV-2 complications.

METHODS

A total of 280 subjects were classified into three groups: COVID-19-negative controls (n = 80), and COVID-19 patients (n=200) who required hospitalization were classified into two groups: group (2) moderate cases (n = 112) and group (3) severe cases (n = 88).

RESULTS

The results showed that the serum GAS5 expression was significantly down-expressed in COVID-19 patients; as a consequence, the expression of miR-200 was reported to be overexpressed and its targeted ACE2 was down-regulated. The ROC curve was drawn to examine the diagnostic abilities of GAS5, miR-200, and ACE2, yielding high diagnostic accuracy with high sensitivity and specificity.

CONCLUSION

lncRNA-GAS5, miRNA-200, and ACE2 panels presented great diagnostic potential as they demonstrated the highest diagnostic accuracy for discriminating moderate COVID-19 and severe COVID-19 cases.

摘要

背景

严重急性呼吸综合征冠状病毒 2(SARS-CoV-2)是导致冠状病毒病(COVID-19)的病原体,它可能产生严重的不良反应,导致全球公共卫生危机。在 COVID-19 中,ACE-2 的缺乏与通过增加血管紧张素 II 水平和降低 ACE-2/ Mas 受体轴活性导致的炎症和细胞因子风暴有关。miRNA 是一种通过与靶向 mRNAs 结合来调节基因表达的小非编码 RNA 序列。miR-200 功能障碍与急性肺损伤后的急性呼吸窘迫综合征的发展有关,并被提议作为 ACE2 表达的关键调节剂。长链非编码 RNA 生长停滞特异性转录物 5(GAS5)最近因其对 miRNA-200/ACE2 轴的调节作用而受到研究。

目的

本研究旨在探讨 lncRNA GAS5、miRNA-200 和 ACE2 作为新的 COVID-19 诊断标志物,预测 SARS-CoV-2 并发症严重程度的作用。

方法

总共 280 名受试者分为三组:COVID-19 阴性对照组(n = 80),需要住院的 COVID-19 患者(n = 200)分为两组:组 2(中度病例,n = 112)和组 3(重度病例,n = 88)。

结果

结果表明,COVID-19 患者血清 GAS5 表达显著下调,miR-200 表达上调,其靶向 ACE2 下调。绘制 ROC 曲线以检验 GAS5、miR-200 和 ACE2 的诊断能力,结果表明它们具有高诊断准确性,具有高灵敏度和特异性。

结论

lncRNA-GAS5、miRNA-200 和 ACE2 联合检测具有很大的诊断潜力,因为它们在区分中度 COVID-19 和重度 COVID-19 病例方面表现出最高的诊断准确性。

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