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多聚肌苷酸胞苷酸诱导的 microRNA-30b-5p 通过靶向 CRFB5 负调控鲤鱼抗病毒免疫反应中的 JAK/STAT 信号通路。

Poly (I:C)-Induced microRNA-30b-5p Negatively Regulates the JAK/STAT Signaling Pathway to Mediate the Antiviral Immune Response in Silver Carp () via Targeting CRFB5.

机构信息

Department of Veterinary Medicine, College of Animal Science and Technology, Jilin Agricultural University, Changchun 130118, China.

出版信息

Int J Mol Sci. 2024 May 24;25(11):5712. doi: 10.3390/ijms25115712.

DOI:10.3390/ijms25115712
PMID:38891899
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11172372/
Abstract

In aquaculture, viral diseases pose a significant threat and can lead to substantial economic losses. The primary defense against viral invasion is the innate immune system, with interferons (IFNs) playing a crucial role in mediating the immune response. With advancements in molecular biology, the role of non-coding RNA (ncRNA), particularly microRNAs (miRNAs), in gene expression has gained increasing attention. While the function of miRNAs in regulating the host immune response has been extensively studied, research on their immunomodulatory effects in teleost fish, including silver carp (), is limited. Therefore, this research aimed to investigate the immunomodulatory role of microRNA-30b-5p (miR-30b-5p) in the antiviral immune response of silver carp () by targeting cytokine receptor family B5 (CRFB5) via the JAK/STAT signaling pathway. In this study, silver carp were stimulated with polyinosinic-polycytidylic acid (poly (I:C)), resulting in the identification of an up-regulated miRNA (miR-30b-5p). Through a dual luciferase assay, it was demonstrated that CRFB5, a receptor shared by fish type I interferon, is a novel target of miR-30b-5p. Furthermore, it was found that miR-30b-5p can suppress post-transcriptional CRFB5 expression. Importantly, this study revealed for the first time that miR-30b-5p negatively regulates the JAK/STAT signaling pathway, thereby mediating the antiviral immune response in silver carp by targeting CRFB5 and maintaining immune system stability. These findings not only contribute to the understanding of how miRNAs act as negative feedback regulators in teleost fish antiviral immunity but also suggest their potential therapeutic measures to prevent an excessive immune response.

摘要

在水产养殖中,病毒性疾病是一个重大威胁,可导致巨大的经济损失。先天免疫系统是抵御病毒入侵的主要防线,干扰素(IFNs)在介导免疫反应中起着关键作用。随着分子生物学的进步,非编码 RNA(ncRNA),特别是 microRNAs(miRNAs)在基因表达中的作用越来越受到关注。虽然 miRNA 调节宿主免疫反应的功能已得到广泛研究,但对包括鲤鱼()在内的硬骨鱼类中其免疫调节作用的研究有限。因此,本研究旨在通过 JAK/STAT 信号通路靶向细胞因子受体家族 B5(CRFB5),研究 microRNA-30b-5p(miR-30b-5p)在鲤鱼抗病毒免疫反应中的免疫调节作用。在这项研究中,用聚肌苷酸-聚胞苷酸(poly(I:C))刺激鲤鱼,鉴定出一个上调的 miRNA(miR-30b-5p)。通过双荧光素酶报告基因实验,证实了 CRFB5,一种鱼类 I 型干扰素的受体,是 miR-30b-5p 的一个新靶点。此外,还发现 miR-30b-5p 可以抑制 CRFB5 的转录后表达。重要的是,本研究首次揭示了 miR-30b-5p 通过靶向 CRFB5 负调控 JAK/STAT 信号通路,从而调节鲤鱼的抗病毒免疫反应,维持免疫系统稳定性。这些发现不仅有助于理解 miRNA 如何作为硬骨鱼类抗病毒免疫的负反馈调节剂发挥作用,还为预防过度免疫反应提供了潜在的治疗措施。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf75/11172372/32c3aeb0dfe5/ijms-25-05712-g006.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf75/11172372/70fc9752de29/ijms-25-05712-g002.jpg
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