MiR‐30a increases <scp>MDSC</scp> differentiation and immunosuppressive function by targeting <scp>SOCS</scp>3 in mice with B‐cell lymphoma

Xu, Zhen; Ji, Jianjian; Xu, Jingjing; Li, Dan; Shi, Guo‐Ping; Liu, Fei; Ding, Liang; Ren, Jing; Dou, Huan; Wang, Tingting; Hou, Yayi

doi:10.1111/febs.14133

Cited by 46 publications

(45 citation statements)

References 38 publications

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“…5). Consistent with our data, during the preparation of this article, a paper published by Xu and colleagues revealed that miR-30a-5p directly targets the 3= UTR of SOCS3 and manipulates the expression of SOCS3 in mouse B cell lymphoma (55). Importantly, we detected decreased expression of miR-30a-5p and increased expression of SOCS1 and SOCS3 in TGEV-infected ileum.…”

Section: Discussionsupporting

confidence: 91%

The Coronavirus Transmissible Gastroenteritis Virus Evades the Type I Interferon Response through IRE1α-Mediated Manipulation of the MicroRNA miR-30a-5p/SOCS1/3 Axis

Wang

Xue

et al. 2018

J Virol

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In host innate immunity, type I interferons (IFN-I) are major antiviral molecules, and coronaviruses have evolved diverse strategies to counter the IFN-I response during infection. Transmissible gastroenteritis virus (TGEV), a member of the family, induces endoplasmic reticulum (ER) stress and significant IFN-I production after infection. However, how TGEV evades the IFN-I antiviral response despite the marked induction of endogenous IFN-I has remained unclear. Inositol-requiring enzyme 1 α (IRE1α), a highly conserved ER stress sensor with both kinase and RNase activities, is involved in the IFN response. In this study, IRE1α facilitated TGEV replication via downmodulating the host microRNA (miR) miR-30a-5p abundance. miR-30a-5p normally enhances IFN-I antiviral activity by directly targeting the negative regulators of Janus family kinase (JAK)-signal transducer and activator of transcription (STAT), the suppressor of cytokine signaling protein 1 (SOCS1), and SOCS3. Furthermore, TGEV infection increased SOCS1 and SOCS3 expression, which dampened the IFN-I antiviral response and facilitated TGEV replication. Importantly, compared with mock infection, TGEV infection resulted in decreased miR-30a-5p levels and significantly elevated SOCS1 and SOCS3 expression in the piglet ileum. Taken together, our data reveal a new strategy used by TGEV to escape the IFN-I response by engaging the IRE1α-miR-30a-5p/SOCS1/3 axis, thus improving our understanding of how TGEV escapes host innate immune defenses. Type I interferons (IFN-I) play essential roles in restricting viral infections. Coronavirus infection induces ER stress and the interferon response, which reflects different adaptive cellular processes. An understanding of how coronavirus-elicited ER stress is actively involved in viral replication and manipulates the host IFN-I response has remained elusive. Here, TGEV inhibited host miR-30a-5p via the ER stress sensor IRE1α, which led to the increased expression of negative regulators of JAK-STAT signaling cascades, namely, SOCS1 and SOCS3. Increased SOCS1 or SOCS3 expression impaired the IFN-I antiviral response, promoting TGEV replication. These findings enhance our understanding of the strategies used by coronaviruses to antagonize IFN-I innate immunity via IRE1α-mediated manipulation of the miR-30a-5p/SOCS axis, highlighting the crucial role of IRE1α in innate antiviral resistance and the potential of IRE1α as a novel target against coronavirus infection.

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Section: Discussionsupporting

confidence: 91%

The Coronavirus Transmissible Gastroenteritis Virus Evades the Type I Interferon Response through IRE1α-Mediated Manipulation of the MicroRNA miR-30a-5p/SOCS1/3 Axis

Wang

Xue

et al. 2018

J Virol

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“…In contrast, ADAR1 overexpression significantly reduced IL-6 levels in the spleen, consistent with IL-6 function as the main inflammatory factor, which attenuates the inflammatory response in sepsis that is inhibited by ADAR1. Previous studies have confirmed that SOCS3 is targeted by miR-30a [14,15]. However, the specific mechanism by which ADAR1 reduces IL-6 expression and alleviates sepsis is not clear.…”

Section: Discussionmentioning

confidence: 99%

“…Suppressor of cytokine signaling 3 (SOCS3) is a feedback inhibitor of the Janus kinase (JAK)/signal sensor and transcriptional activation 3 (STAT3) signaling pathway, which mediates the signal transduction of many cytokines and has been implicated in multiple infectious and inflammatory diseases [12]. Studies have shown that SOCS3 is regulated by miR-30a and miR-30a-5p [13][14][15].…”

Section: Introductionmentioning

confidence: 99%

“…Experiments have shown that miR-30a-5p can regulate the occurrence and development of allergic disease by targeting the inhibition of SOCS3 expression [13]. Overexpression of miR-30a can specifically inhibit SOCS3 expression and enhance myeloid-derived suppressor cell differentiation and immunosuppression in mice with B-cell lymphoma [14]. However, downregulation of miR-30a can inhibit the JAK/STAT3 pathway by targeting SOCS3 and reducing the tumorforming ability of glioma stem cells [15].…”

mentioning

confidence: 99%

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ADAR1 Alleviates Inflammation in a Murine Sepsis Model via the ADAR1-miR-30a-SOCS3 Axis

Zhou

Liu

Zhao

et al. 2020

Mediators of Inflammation

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Adenosine deaminase acting on double-stranded RNA 1 (ADAR1) mediates adenosine-to-inosine (A-to-I) RNA editing events. ADAR1 is highly expressed in “septic” macrophages and in small intestinal tissues of mice with sepsis. Overexpression of ADAR1 suppresses inflammation and intestinal damage. However, the specific underlying mechanism is unclear. This study was conducted to explore how microRNA (miRNA) regulates the anti-inflammatory mechanism of macrophages following ADAR1 upregulation. A murine sepsis model was established by cecal ligation and puncture (CLP). Mice were randomly assigned to sham, CLP, and CLP+ADAR1 groups. Hematoxylin and eosin (HE) staining and fluorescence isothiocyanate-dextran were used to evaluate intestinal injury and permeability. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR), western blotting, and Luminex assays were performed to detect changes in the expression of inflammatory cytokines. Adenoviruses were used to express ADAR1 in RAW 264.7 cells. Ribonucleoprotein immunoprecipitation analysis was conducted to detect the binding of ADAR1 and miRNAs. A dual-luciferase reporter assay was used to detect the binding of miRNAs and regulatory factors. We observed that ADAR1 significantly increased the expression of suppressor of cytokine signaling 3 (SOCS3) in macrophages and reduced the expression of interleukin-6 in macrophages and the serum, thereby reducing intestinal permeability and mucosal injury in mice with sepsis. The RNA-ribonucleoprotein immunoprecipitation binding assay and qRT-PCR demonstrated a direct interaction between ADAR1 and pri-miR-30a. The luciferase assay demonstrated that SOCS3 was significantly inhibited by miR-30a-5p, the mature product of miR-30a. Thus, ADAR1 exerts a protective effect against sepsis by reducing inflammation and organ damage via the ADAR1-miR-30a-SOCS3 axis.

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“…A recent study revealed that miR-30a as a member of the miR-30 family increases the differentiation of MDSCs and their immunosuppressive activity through regulating SOCS3 in B-cell lymphoma model mice. Xu et al ( 82 ) detected augmented expression of miR-30a in PMN-MDSCs and M-MDSCs in mice with B cell lymphoma. MicroRNA-30a targets SOCS3, which is a JAK2/STAT3 pathway regulator.…”

Section: Micro Rnasmentioning

confidence: 99%

MicroRNAs and lncRNAs—A New Layer of Myeloid-Derived Suppressor Cells Regulation

et al. 2020

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Myeloid-derived suppressor cells (MDSCs) constitute an important component in regulating immune responses in several abnormal physiological conditions such as cancer. Recently, novel regulatory tumor MDSC biology modulating mechanisms, including differentiation, expansion and function, were defined. There is growing evidence that miRNAs and long non-coding RNAs (lncRNA) are involved in modulating transcriptional factors to become complex regulatory networks that regulate the MDSCs in the tumor microenvironment. It is possible that aberrant expression of miRNAs and lncRNA contributes to MDSC biological characteristics under pathophysiological conditions. This review provides an overview on miRNAs and lncRNAs epiregulation of MDSCs development and immunosuppressive functions in cancer.

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MiR‐30a increases MDSC differentiation and immunosuppressive function by targeting SOCS3 in mice with B‐cell lymphoma

Cited by 46 publications

References 38 publications

The Coronavirus Transmissible Gastroenteritis Virus Evades the Type I Interferon Response through IRE1α-Mediated Manipulation of the MicroRNA miR-30a-5p/SOCS1/3 Axis

The Coronavirus Transmissible Gastroenteritis Virus Evades the Type I Interferon Response through IRE1α-Mediated Manipulation of the MicroRNA miR-30a-5p/SOCS1/3 Axis

ADAR1 Alleviates Inflammation in a Murine Sepsis Model via the ADAR1-miR-30a-SOCS3 Axis

MicroRNAs and lncRNAs—A New Layer of Myeloid-Derived Suppressor Cells Regulation

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