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microRNAs 和长非编码 RNA 在 COVID-19 中的新兴作用及其对治疗的影响。

Emerging role of microRNAs and long non-coding RNAs in COVID-19 with implications to therapeutics.

机构信息

Institut de recherches cliniques de Montréal, Montréal, QC H2W 1R7, Canada.

Institut de recherches cliniques de Montréal, Montréal, QC H2W 1R7, Canada.

出版信息

Gene. 2023 Apr 20;861:147232. doi: 10.1016/j.gene.2023.147232. Epub 2023 Feb 2.

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection which is commonly known as COVID-19 (COronaVIrus Disease 2019) has creeped into the human population taking tolls of life and causing tremendous economic crisis. It is indeed crucial to gain knowledge about their characteristics and interactions with human host cells. It has been shown that the majority of our genome consists of non-coding RNAs. Non-coding RNAs including micro RNAs (miRNAs) and long non-coding RNAs (lncRNAs) display significant roles in regulating gene expression in almost all cancers and viral diseases. It is intriguing that miRNAs and lncRNAs remarkably regulate the function and expression of major immune components of SARS-CoV-2. MiRNAs act via RNA interference mechanism in which they bind to the complementary sequences of the viral RNA strand, inducing the formation of silencing complex that eventually degrades or inhibits the viral RNA and viral protein expression. LncRNAs have been extensively shown to regulate gene expression in cytokine storm and thus emerges as a critical target for COVID-19 treatment. These lncRNAs also act as competing endogenous RNAs (ceRNAs) by sponging miRNAs and thus affecting the expression of downstream targets during SARS-CoV-2 infection. In this review, we extensively discuss the role of miRNAs and lncRNAs, describe their mechanism of action and their different interacting human targets cells during SARS-CoV-2 infection. Finally, we discuss possible ways how an interference with their molecular function could be exploited for new therapies against SARS-CoV-2.

摘要

严重急性呼吸综合征冠状病毒 2(SARS-CoV-2)感染通常被称为 COVID-19(COronaVIrus Disease 2019),已悄然潜入人类群体,造成生命损失并引发巨大的经济危机。了解其特征及其与人类宿主细胞的相互作用至关重要。事实证明,我们的大部分基因组由非编码 RNA 组成。非编码 RNA 包括 microRNAs(miRNAs)和长非编码 RNA(lncRNAs),在几乎所有癌症和病毒疾病中都显示出对基因表达的重要调节作用。有趣的是,miRNAs 和 lncRNAs 显著调节 SARS-CoV-2 的主要免疫成分的功能和表达。miRNAs 通过 RNA 干扰机制发挥作用,它们与病毒 RNA 链的互补序列结合,诱导沉默复合物的形成,最终降解或抑制病毒 RNA 和病毒蛋白的表达。lncRNAs 已广泛证明可调节细胞因子风暴中的基因表达,因此成为 COVID-19 治疗的关键靶点。这些 lncRNAs 还可以作为竞争性内源 RNA(ceRNA)通过吸附 miRNAs 从而影响 SARS-CoV-2 感染过程中下游靶基因的表达。在这篇综述中,我们广泛讨论了 miRNAs 和 lncRNAs 的作用,描述了它们的作用机制以及它们在 SARS-CoV-2 感染过程中与不同的人类靶细胞相互作用的方式。最后,我们讨论了干扰它们的分子功能如何被用于开发针对 SARS-CoV-2 的新疗法。

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