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轮状病毒介导的 microRNA-192 家族和 microRNA-181a 的抑制激活 Wnt/β-连环蛋白信号通路:一项体外研究。

Rotavirus-Mediated Suppression of miRNA-192 Family and miRNA-181a Activates Wnt/β-Catenin Signaling Pathway: An In Vitro Study.

机构信息

Division of Virology, ICMR-National AIDS Research Institute, Pune 411026, India.

Division of Virology, ICMR-National Institute of Cholera and Enteric Diseases, Kolkata 700010, India.

出版信息

Viruses. 2022 Mar 9;14(3):558. doi: 10.3390/v14030558.

Abstract

The significance of the Wnt/β-catenin signaling cascade in Rotavirus (RV) infection has not been elucidated. In this study, we attempt to elucidate the importance of the Wnt/β-catenin pathway in the RV pathogenesis and investigate a miRNA-mediated approach to regulate the pathway to repress the RV infection in the host. The regulation of the Wnt signaling pathway in terms of β-catenin accumulation and activation was analyzed by Western blotting and Confocal imaging analysis. The expression levels of miR-192 family members and miR-181a were enquired into using qPCR assays, whereas their targets in the Wnt pathway were confirmed using the Luciferase Reporter Assays. Members of the miR-192 family and miR-181a, which target the components of the pathway, were also found to be considerably decreased in expression during RV infection. Ectopic expression of these miRNAs could restrict the RV pathogenesis by targeting the intermediates of the Wnt signaling pathway. The miR-192 family and miR-181a were capable of suppressing the RV infection via targeting of the Wnt/β-catenin pathway. The study not only highlights the role of the Wnt signaling cascade in RV infection but also suggests that miRNAs can synergistically decrease RV replication by a significant amount. Thus, the miR-192 family and miR-181a present themselves as prospective antivirals against RV infection.

摘要

Wnt/β-catenin 信号级联在轮状病毒 (RV) 感染中的意义尚未阐明。在本研究中,我们试图阐明 Wnt/β-catenin 途径在 RV 发病机制中的重要性,并研究一种 miRNA 介导的方法来调节该途径,以抑制宿主中的 RV 感染。通过 Western blot 和共聚焦成像分析来分析 Wnt 信号通路在 β-catenin 积累和激活方面的调控。使用 qPCR 检测 miR-192 家族成员和 miR-181a 的表达水平,而使用 Luciferase Reporter assays 来确认 Wnt 途径中的靶标。在 RV 感染过程中,靶向途径成分的 miR-192 家族和 miR-181a 的成员也被发现表达显著下调。这些 miRNA 的异位表达可以通过靶向 Wnt 信号通路的中间物来限制 RV 的发病机制。miR-192 家族和 miR-181a 可以通过靶向 Wnt/β-catenin 途径来抑制 RV 感染。该研究不仅强调了 Wnt 信号级联在 RV 感染中的作用,还表明 miRNA 可以通过大量协同作用显著抑制 RV 复制。因此,miR-192 家族和 miR-181a 本身可作为针对 RV 感染的潜在抗病毒药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8723/8955121/903aab60e53a/viruses-14-00558-g001.jpg

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