文章基本信息

标题：MicroRNA-127 Promotes Anti-microbial Host Defense through Restricting A20-Mediated De-ubiquitination of STAT3
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作者：Xiaoyi Liu ; Yun Mao ; Yanhua Kang 等
期刊名称：iScience
印刷版ISSN：2589-0042
出版年度：2020
卷号：23
期号：1
页码：1-23
DOI：10.1016/j.isci.2019.100763
语种：English
出版社：Elsevier
摘要：SummaryThe increasing rising of multiple drug-resistantStaphylococcus aureushas become a major public health concern, underscoring a pressing need for developing therapies essentially based on the understanding of host defensive mechanism. In the present study, we showed that microRNA (miR)-127 played a key role in controlling bacterial infection and conferred a profound protection against staphylococcal pneumonia. The protective effect of miR-127 was largely dependent on its regulation of macrophage bactericidal activity and the generation of IL-22, IL-17, and anti-microbial peptides (AMPs), the pathway primarily driven by STAT3. Importantly, we revealed that the ubiquitin-editing enzyme A20, a genuine target of miR-127, specifically interacted with and repressed K63-ubiquitination of STAT3, thereby compromising its phosphorylation upon bacterial infection. Thus, our data not only identify miR-127 as a non-coding molecule with anti-bacterial activity but also delineate an unappreciated mechanism whereby A20 regulates STAT3-driven anti-microbial signaling via modulating its ubiquitination.Graphical AbstractDisplay OmittedHighlights•miR-127 confers the protection against staphylococcal pneumonia•miR-127 augments macrophage anti-microbial responses by regulating STAT3 activity•A20 directly interacts and represses STAT3 K63-ubiquitination•The A20/STAT3 axis mediates the anti-microbial role of miR-127Molecular Mechanism of Behavior; Immunology; Microbiology; Bacteriology