MicroRNA-127 Promotes Anti-microbial Host Defense Through Restricting A20-Mediated De-ubiquitination of STAT3

Overview

Journal iScience

Publisher Cell Press

Date 2020 Jan 21

PMID 31958753

Citations 9

Authors

Xiaoyi Liu

Yun Mao

Yanhua Kang

Long He

Bo Zhu

Wei Zhang

Yin Lu

Qinan Wu

Dakang Xu

Liyun Shi

Affiliations

Soon will be listed here.

Abstract

The increasing rising of multiple drug-resistant Staphylococcus aureus has 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.

Citing Articles

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