The zinc finger protein Miz1 suppresses liver tumorigenesis by restricting hepatocyte-driven macrophage activation and inflammation

doi:10.1016/j.immuni.2021.04.027

	The zinc finger protein Miz1 suppresses liver tumorigenesis by restricting hepatocyte-driven macrophage activation and inflammation
	Zhang, Wenjie 1,2; Zhangyuan, Guangyan 1,2; Wang, Fei 1,2; Jin, Kangpeng 1,2; Shen, Haiyuan 1,2; Zhang, Liansheng 3,4; Yuan, Xiang 3,4; Wang, Jincheng 1,2; Zhang, Haitian 1,2; Yu, Weiwei 1,2; Huang, Ruyi 1,2; Xu, Xiaoliang 1,2; Yin, Yin 1,2; Zhong, Guisheng5 ; Lin, Anning 4,6; Sun, Beicheng 1,2
	2021-06-08
发表期刊	IMMUNITY (IF:25.5[JCR-2023],33.2[5-Year])
ISSN	1074-7613
EISSN	1097-4180
卷号	54 期号:6 页码:1168
DOI	10.1016/j.immuni.2021.04.027
摘要	Chronic inflammation plays a central role in hepatocellular carcinoma (HCC), but the contribution of hepatocytes to tumor-associated inflammation is not clear. Here, we report that the zinc finger transcription factor Miz1 restricted hepatocyte-driven inflammation to suppress HCC, independently of its transcriptional activity. Miz1 was downregulated in HCC mouse models and a substantial fraction of HCC patients. Hepatocyte-specific Miz1 deletion in mice generated a distinct sub-group of hepatocytes that produced pro-inflammatory cytokines and chemokines, which skewed the polarization of the tumor-infiltrating macrophages toward pro-inflammatory phenotypes to promote HCC. Mechanistically, Miz1 sequestrated the oncoprotein metadherin (MTDH), preventing MTDH from promoting transcription factor nuclear factor kappa B (NF-kappa B) activation. A distinct sub-group of pro-inflammatory cytokine-producing hepatocytes was also seen in a subset of HCC patients. In addition, Miz1 expression inversely correated with disease recurrence and poor prognosis in HCC patients. Our findings identify Miz1 as a tumor suppressor that prevents hepatocytes from driving inflammation in HCC.
收录类别	SCIE
语种	英语
WOS研究方向	Immunology
WOS类目	Immunology
WOS记录号	WOS:000659882900010
出版者	CELL PRESS
原始文献类型	Article
引用统计	正在获取...
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/127611
专题	iHuman研究所_PI研究组_钟桂生组生命科学与技术学院
通讯作者	Lin, Anning; Sun, Beicheng
作者单位	1.Nanjing Univ Med Sch, Dept Hepatobiliary Surg, Affiliated Drum Tower Hosp, Nanjing 210008, Peoples R China; 2.Nanjing Med Univ, Liver Transplantat Ctr, Affiliated Hosp 1, Nanjing, Jiangsu, Peoples R China; 3.Chinese Acad Sci, Shanghai Inst Biochem & Cell Biol, State Key Lab Cell Biol, Shanghai 200031, Peoples R China; 4.Univ Chicago, Ben May Dept Canc Res, Chicago, IL 60637 USA; 5.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China; 6.Nanjing Univ, Inst Modern Biol, Nanjing 20018, Peoples R China
推荐引用方式 GB/T 7714	Zhang, Wenjie,Zhangyuan, Guangyan,Wang, Fei,et al. The zinc finger protein Miz1 suppresses liver tumorigenesis by restricting hepatocyte-driven macrophage activation and inflammation[J]. IMMUNITY,2021,54(6):1168.
APA	Zhang, Wenjie.,Zhangyuan, Guangyan.,Wang, Fei.,Jin, Kangpeng.,Shen, Haiyuan.,...&Sun, Beicheng.(2021).The zinc finger protein Miz1 suppresses liver tumorigenesis by restricting hepatocyte-driven macrophage activation and inflammation.IMMUNITY,54(6),1168.
MLA	Zhang, Wenjie,et al."The zinc finger protein Miz1 suppresses liver tumorigenesis by restricting hepatocyte-driven macrophage activation and inflammation".IMMUNITY 54.6(2021):1168.