靶向ACE2基因的mirna在COVID-19中的生物信息学评价

M. Rafat, Aida Roshan, Mahya Abyar, Saba Keramati, A. Nikpoor
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引用次数: 1

摘要

2019年底在中国武汉开始的急性呼吸综合征冠状病毒2 (SARS-CoV-2)已成为全球流行病。血管紧张素2转换酶(ACE2)作为宿主功能受体引起急性冠状病毒急性呼吸综合征(SARS-CoV-2)。ACE2在人体不同器官的不同细胞中大量表达。在人体生理学中,ACE2通过降解血管紧张素II在肾素-血管紧张素-醛固酮(RAAS)系统中发挥重要作用。许多因素与ACE2表达的改变和COVID-19的严重程度和进展有关,包括可能在其中有效的microrna。确定SARS-CoV-2感染引起的病理变化非常重要,因为它对了解COVID-19的病理生理学和制定循证治疗策略具有重要意义。目前,正在进行的临床试验正在探索许多干预策略。目的:利用生物信息学数据库,通过降低病毒基因表达抑制病毒进入和复制的宿主microRNAs (miRNAs),寻找潜在的抗病毒治疗方法。方法:采用TargetScan、DIANA、ENCORI和miRWalk数据库中的不同算法,鉴定靶向ACE2的潜在microrna。然后,根据microrna种子区与ACE2基因3′-UTR区的亲和力,对候选microrna进行评分。最后,选择得分较高的microrna作为实际分析的候选物。结果:生物信息学分析结果显示,Has-miR-200c-3p、Has-miR-29a、Has-miR-29c和Has-miR-942最有可能抑制ACE2。这些microrna是在毒力期间可能影响ACE2的最有效因素。结论:ACE2似乎受miR-200c-3p的调控,在病理生理过程中起着至关重要的作用。因此,该microRNA可作为一个合适的新候选物进行实验评价。
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Bioinformatic Evaluation of the miRNAs Targeting ACE2 Gene in COVID-19
Introduction: Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), which began in late 2019 in Wuhan, China, has become a global epidemic. Angiotensin 2 converting enzyme (ACE2) acts as a receptor for host function to cause acute coronavirus 2 acute respiratory syndrome (SARS-CoV-2). ACE2 is abundantly expressed in different cells of different human organs. In human physiology, ACE2 is a major player in the renin-angiotensin-aldosterone (RAAS) system by degrading angiotensin II. Many factors have been associated with altered ACE2 expression and the severity and progression of COVID-19, including microRNAs that may be effective in it. Identifying pathological changes due to SARS-CoV-2 infection is important because it has major implications for understanding the pathophysiology of COVID-19 and developing evidence-based treatment strategies. Currently, many intervention strategies are being explored in ongoing clinical trials. Objective: The aim of this study is to use bioinformatics databases to find potential antiviral therapies against SARS-CoV-2 through host microRNAs (miRNAs) that can reduce viral gene expression to inhibit virus entry and replication. Methods: Using different algorithms in TargetScan, DIANA, ENCORI and miRWalk databases, the potential microRNAs were identified that target ACE2. Then, a score table was prepared from the candidate microRNAs, based on the affinity of the seed region of microRNAs and the 3`-UTR region of the ACE2 gene. Finally, microRNAs with higher scores were chosen as candidates for practical analysis. Results: The results of Bioinformatical analysis showed that Has-miR-200c-3p, Has-miR-29a, Has-miR-29c, and Has-miR-942 are most likely to inhibit ACE2. These microRNAs are the most potent factors that might be affected on ACE2 during virulence. Conclusion: It seems that ACE2 is under the control of the miR-200c-3p and plays a crucial role in the pathophysiology process. Therefore, this microRNA can be considered as a suitable new candidate for experimental evaluation.
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