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

Xiaoyi Liu; Yun Mao; Yanhua Kang; Long He; Bo Zhu; Wei Zhang; Yin Lu; Qinan Wu; Dakang Xu; Liyun Shi

doi:10.1016/j.isci.2019.100763

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

iScience. 2020 Jan 24;23(1):100763. doi: 10.1016/j.isci.2019.100763. Epub 2019 Dec 10.

Authors

Xiaoyi Liu¹, Yun Mao², Yanhua Kang³, Long He¹, Bo Zhu¹, Wei Zhang¹, Yin Lu⁴, Qinan Wu⁵, Dakang Xu⁶, Liyun Shi⁷

Affiliations

¹ Department of Immunology and Medical Microbiology, Nanjing University of Chinese Medicine, Nanjing, China.
² Key Laboratory of Inflammation and Immunoregulation, Hangzhou Normal University School of Medicine, Hangzhou, China.
³ Department of Immunology and Medical Microbiology, Nanjing University of Chinese Medicine, Nanjing, China; Key Laboratory of Inflammation and Immunoregulation, Hangzhou Normal University School of Medicine, Hangzhou, China.
⁴ Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, China.
⁵ Collaborative Innovation Centers of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, Nanjing, China.
⁶ Faculty of Medical Laboratory Science, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China; Hudson Institute of Medical Research, Department of Molecular and Translational Science, Monash University, Clayton, VIC 3800, Australia.
⁷ Department of Immunology and Medical Microbiology, Nanjing University of Chinese Medicine, Nanjing, China; Key Laboratory of Inflammation and Immunoregulation, Hangzhou Normal University School of Medicine, Hangzhou, China. Electronic address: shi_liyun@msn.com.

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.

Keywords: Bacteriology; Immunology; Microbiology; Molecular Mechanism of Behavior.