MicroRNA-149* suppresses hepatic inflammatory response through antagonizing STAT3 signaling pathway
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Qiqi Zhang1,*, Jia Su1,*, Ziwei Wang1, Hui Qi2, Zeyong Ge2, Zhijun Li3, Wei-Dong Chen2,3 and Yan-Dong Wang1
1State Key Laboratory of Chemical Resource Engineering, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing, P. R. China
2Key Laboratory of Receptors-Mediated Gene Regulation and Drug Discovery, School of Medicine, Henan University, Kaifeng, P. R. China
3Key Laboratory of Molecular Pathology, School of Basic Medical Science, Inner Mongolia Medical University, Hohhot, P. R. China
*These authors contributed equally to this work
Yan-Dong Wang, email: [email protected]
Wei-Dong Chen, email: [email protected]
Keywords: miR-149*, liver inflammation, STAT3, miRNA, CRISPR/CAS9
Received: December 01, 2016 Accepted: June 05, 2017 Published: June 16, 2017
Chronic inflammation is increasingly recognized as an important component of tumorigenesis and metabolic diseases. The roles of microRNA149* (miRNA149*) in inflammation remain poorly understood. Here, we demonstrate that miR-149* is a suppressor of STAT3-mediated inflammation. MiR-149*−/− mice were generated with CRISPR/CAS9 technique. In a lipopolysaccharide (LPS)-induced inflammation model, miR-149*−/− mice show more severe liver injury and inflammation, compared with wild-type (WT) mice. MiR-149*−/− mice also displayed elevated messenger RNA (mRNA) levels of interleukin (IL)-6, inducible nitric oxide synthase (iNOS), complement C3 (C3) and IL-4 in response to LPS. Then miR-149* agomir administration is largely able to alleviate the LPS-induced some inflammatory gene expression in WT mouse liver. In vitro, miR-149* mimics inhibited expression of STAT3-meidated inflammatory mediators induced by LPS and suppresses the phosphorylation of STAT3 and its transcription activity in HepG2 cells. These findings identify miR-149* as a negative mediator of inflammation that may serve as an attractive therapeutic tool for immune and inflammatory liver diseases.
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