microRNA-34 mediates a negative feedback loop in the JAK-STAT pathway to attenuate immune overactivation in an invertebrate

Abstract The JAK-STAT pathway is an essential signaling mechanism that initiates immune responses against pathogen infections. The intrinsic homeostatic regulation of JAK-STAT signaling is critical for maintaining immune homeostasis. Previous studies have shown that aberrant activation of the invert...

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Main Authors: Hongliang Zuo, Alian Liao, Sihui Shen, Youxi Wang, Xiya Yang, Shaoping Weng, Jianguo He, Xiaopeng Xu
Format: Article
Language:English
Published: BMC 2025-05-01
Series:Cell Communication and Signaling
Online Access:https://doi.org/10.1186/s12964-025-02230-y
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author Hongliang Zuo
Alian Liao
Sihui Shen
Youxi Wang
Xiya Yang
Shaoping Weng
Jianguo He
Xiaopeng Xu
author_facet Hongliang Zuo
Alian Liao
Sihui Shen
Youxi Wang
Xiya Yang
Shaoping Weng
Jianguo He
Xiaopeng Xu
author_sort Hongliang Zuo
collection DOAJ
description Abstract The JAK-STAT pathway is an essential signaling mechanism that initiates immune responses against pathogen infections. The intrinsic homeostatic regulation of JAK-STAT signaling is critical for maintaining immune homeostasis. Previous studies have shown that aberrant activation of the invertebrate JAK-STAT pathway leads to inflammation-like symptoms. Understanding the homeostatic mechanisms of this pathway in invertebrates is of significant interest. Pacific white shrimp (Penaeus vannamei) is one of the most extensively studied invertebrates in immune system research. In this study, we demonstrate that the shrimp microRNA-34 (miR-34) attenuates JAK-STAT pathway activation by targeting JAK, thereby inhibiting STAT phosphorylation and nuclear translocation. Interestingly, miR-34 expression is directly regulated by STAT, forming a negative feedback regulatory loop in the JAK-STAT pathway. Disrupting this loop results in excessive JAK-STAT pathway activation and immune overactivation, exacerbating inflammation caused by Vibrio parahaemolyticus infection in shrimp. This study provides new insights into the regulatory mechanism of the JAK-STAT pathway and its roles in maintaining immune homeostasis in invertebrates.
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institution OA Journals
issn 1478-811X
language English
publishDate 2025-05-01
publisher BMC
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series Cell Communication and Signaling
spelling doaj-art-296c63d44ee2419489ce4616ef5932392025-08-20T01:51:28ZengBMCCell Communication and Signaling1478-811X2025-05-0123111310.1186/s12964-025-02230-ymicroRNA-34 mediates a negative feedback loop in the JAK-STAT pathway to attenuate immune overactivation in an invertebrateHongliang Zuo0Alian Liao1Sihui Shen2Youxi Wang3Xiya Yang4Shaoping Weng5Jianguo He6Xiaopeng Xu7State Key Laboratory of Biocontrol, School of Life Sciences/ Southern Marine Science and Engineering Guangdong Laboratory (Zhuhai)/ China-ASEAN Belt and Road Joint Laboratory on Mariculture Technology, Sun Yat-sen UniversityState Key Laboratory of Biocontrol, School of Life Sciences/ Southern Marine Science and Engineering Guangdong Laboratory (Zhuhai)/ China-ASEAN Belt and Road Joint Laboratory on Mariculture Technology, Sun Yat-sen UniversityState Key Laboratory of Biocontrol, School of Life Sciences/ Southern Marine Science and Engineering Guangdong Laboratory (Zhuhai)/ China-ASEAN Belt and Road Joint Laboratory on Mariculture Technology, Sun Yat-sen UniversityState Key Laboratory of Biocontrol, School of Life Sciences/ Southern Marine Science and Engineering Guangdong Laboratory (Zhuhai)/ China-ASEAN Belt and Road Joint Laboratory on Mariculture Technology, Sun Yat-sen UniversityState Key Laboratory of Biocontrol, School of Life Sciences/ Southern Marine Science and Engineering Guangdong Laboratory (Zhuhai)/ China-ASEAN Belt and Road Joint Laboratory on Mariculture Technology, Sun Yat-sen UniversityState Key Laboratory of Biocontrol, School of Life Sciences/ Southern Marine Science and Engineering Guangdong Laboratory (Zhuhai)/ China-ASEAN Belt and Road Joint Laboratory on Mariculture Technology, Sun Yat-sen UniversityState Key Laboratory of Biocontrol, School of Life Sciences/ Southern Marine Science and Engineering Guangdong Laboratory (Zhuhai)/ China-ASEAN Belt and Road Joint Laboratory on Mariculture Technology, Sun Yat-sen UniversityState Key Laboratory of Biocontrol, School of Life Sciences/ Southern Marine Science and Engineering Guangdong Laboratory (Zhuhai)/ China-ASEAN Belt and Road Joint Laboratory on Mariculture Technology, Sun Yat-sen UniversityAbstract The JAK-STAT pathway is an essential signaling mechanism that initiates immune responses against pathogen infections. The intrinsic homeostatic regulation of JAK-STAT signaling is critical for maintaining immune homeostasis. Previous studies have shown that aberrant activation of the invertebrate JAK-STAT pathway leads to inflammation-like symptoms. Understanding the homeostatic mechanisms of this pathway in invertebrates is of significant interest. Pacific white shrimp (Penaeus vannamei) is one of the most extensively studied invertebrates in immune system research. In this study, we demonstrate that the shrimp microRNA-34 (miR-34) attenuates JAK-STAT pathway activation by targeting JAK, thereby inhibiting STAT phosphorylation and nuclear translocation. Interestingly, miR-34 expression is directly regulated by STAT, forming a negative feedback regulatory loop in the JAK-STAT pathway. Disrupting this loop results in excessive JAK-STAT pathway activation and immune overactivation, exacerbating inflammation caused by Vibrio parahaemolyticus infection in shrimp. This study provides new insights into the regulatory mechanism of the JAK-STAT pathway and its roles in maintaining immune homeostasis in invertebrates.https://doi.org/10.1186/s12964-025-02230-y
spellingShingle Hongliang Zuo
Alian Liao
Sihui Shen
Youxi Wang
Xiya Yang
Shaoping Weng
Jianguo He
Xiaopeng Xu
microRNA-34 mediates a negative feedback loop in the JAK-STAT pathway to attenuate immune overactivation in an invertebrate
Cell Communication and Signaling
title microRNA-34 mediates a negative feedback loop in the JAK-STAT pathway to attenuate immune overactivation in an invertebrate
title_full microRNA-34 mediates a negative feedback loop in the JAK-STAT pathway to attenuate immune overactivation in an invertebrate
title_fullStr microRNA-34 mediates a negative feedback loop in the JAK-STAT pathway to attenuate immune overactivation in an invertebrate
title_full_unstemmed microRNA-34 mediates a negative feedback loop in the JAK-STAT pathway to attenuate immune overactivation in an invertebrate
title_short microRNA-34 mediates a negative feedback loop in the JAK-STAT pathway to attenuate immune overactivation in an invertebrate
title_sort microrna 34 mediates a negative feedback loop in the jak stat pathway to attenuate immune overactivation in an invertebrate
url https://doi.org/10.1186/s12964-025-02230-y
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