Imbalance of TGF-beta 1/BMP-7 pathways induced by M2-polarized macrophages promotes hepatocellular carcinoma aggressiveness

doi:10.1016/j.ymthe.2021.02.016

	Imbalance of TGF-beta 1/BMP-7 pathways induced by M2-polarized macrophages promotes hepatocellular carcinoma aggressiveness
	Ning, Junya 1,2; Ye, Yingnan 1; Bu, Dechao 3; Zhao, Gang 5; Song, Tianqiang 6; Liu, Pengpeng 1; Yu, Wenwen 2; Wang, Hailong 7; Li, Hui 5; Ren, Xiubao 2; Ying, Guoguang 7; Zhao, Yi 3,4; Yu, Jinpu 1,2
	2021-06-02
发表期刊	MOLECULAR THERAPY
ISSN	1525-0016
卷号	29 期号:6 页码:2067-2087
摘要	The transforming growth factor-beta (TGF-beta) signaling pathway is the predominant cytokine signaling pathway in the development and progression of hepatocellular carcinoma (HCC). Bone morphogenetic protein (BMP), another member of the TGF-beta superfamily, has been frequently found to participate in crosstalk with the TGF-beta pathway. However, the complex interaction between the TGF-beta and BMP pathways has not been fully elucidated in HCC. We found that the imbalance of TGF-beta 1/ BMP-7 pathways was associated with aggressive pathological features and poor clinical outcomes in HCC. The induction of the imbalance of TGF-beta 1/BMP-7 pathways in HCC cells could significantly promote HCC cell invasion and stemness by increasing inhibitor of differentiation 1 (ID1) expression. We also found that the microRNA (miR)-17-92 cluster, originating from the extracellular vesicles (EVs) of M2-polarized tumor-associated macrophages (M2-TAMs), stimulated the imbalance of TGF-beta 1/BMP-7 pathways in HCC cells by inducing TGF-beta type II receptor (TGFBR2) post-transcriptional silencing and inhibiting activin A receptor type 1 (ACVR1) post-translational ubiquitylation by targeting Smad ubiquitylation regulatory factor 1 (Smurf1). In vivo, short hairpin (sh)-MIR17HG and ACVR1 inhibitors profoundly attenuated HCC cell growth and metastasis by rectifying the imbalance of TGF-beta 1/BMP-7 pathways. Therefore, we proposed that the imbalance of TGF-beta 1/ BMP-7 pathways is a feasible prognostic biomarker and recovering the imbalance of TGF-beta 1/BMP-7 pathways might be a potential therapeutic strategy for HCC.
DOI	10.1016/j.ymthe.2021.02.016
收录类别	SCI
语种	英语
资助项目	National Natural Science Foundation of China[82002601] ; National Natural Science Foundation of China[82072588] ; National Natural Science Foundation of China[81872143] ; Projects of Science and Technology of Tianjin[18JCQNJC82700] ; Key Project of Tianjin Health and Family Planning Commission[16KG126]
WOS研究方向	Biotechnology & Applied Microbiology ; Genetics & Heredity ; Research & Experimental Medicine
WOS类目	Biotechnology & Applied Microbiology ; Genetics & Heredity ; Medicine, Research & Experimental
WOS记录号	WOS:000657395200017
出版者	CELL PRESS
引用统计	被引频次：61[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	http://119.78.100.204/handle/2XEOYT63/17588
专题	中国科学院计算技术研究所期刊论文_英文
通讯作者	Zhao, Yi; Yu, Jinpu
作者单位	1.Tianjin Med Univ Canc Inst & Hosp, Key Lab Canc Prevent & Therapy, Natl Clin Res Ctr Caner, Tianjins Clin Res Ctr Canc,Canc Mol Diagnost Core, Tianjin 300060, Peoples R China 2.Tianjin Med Univ Canc Inst & Hosp, Natl Clin Res Ctr Caner, Key Lab Canc Immunol & Biotherapy, Tianjins Clin Res Ctr Canc,Dept Immunol, Tianjin 300060, Peoples R China 3.Chinese Acad Sci, Inst Comp Technol, Adv Comp Res Ctr, Key Lab Intelligent Informat Proc, Beijing 100190, Peoples R China 4.Univ China Acad Sci, Ningbo Inst Life & Hlth Ind, Hangzhou 315000, Zhejiang, Peoples R China 5.Tianjin Med Univ Canc Inst & Hosp, Dept Gastrointestinal Canc Biol, Natl Clin Res Ctr Caner, Key Lab Canc Immunol & Biotherapy,Tianjins Clin R, Tianjin 300060, Peoples R China 6.Tianjin Med Univ Canc Inst & Hosp, Dept Liver Canc, Natl Clin Res Ctr Caner, Key Lab Canc Immunol & Biotherapy,Tianjins Clin R, Tianjin 300060, Peoples R China 7.Tianjin Med Univ Canc Inst & Hosp, Lab Canc Cell Biol, Natl Clin Res Ctr Caner, Key Lab Canc Immunol & Biotherapy,Tianjins Clin R, Tianjin 300060, Peoples R China
推荐引用方式 GB/T 7714	Ning, Junya,Ye, Yingnan,Bu, Dechao,et al. Imbalance of TGF-beta 1/BMP-7 pathways induced by M2-polarized macrophages promotes hepatocellular carcinoma aggressiveness[J]. MOLECULAR THERAPY,2021,29(6):2067-2087.
APA	Ning, Junya.,Ye, Yingnan.,Bu, Dechao.,Zhao, Gang.,Song, Tianqiang.,...&Yu, Jinpu.(2021).Imbalance of TGF-beta 1/BMP-7 pathways induced by M2-polarized macrophages promotes hepatocellular carcinoma aggressiveness.MOLECULAR THERAPY,29(6),2067-2087.
MLA	Ning, Junya,et al."Imbalance of TGF-beta 1/BMP-7 pathways induced by M2-polarized macrophages promotes hepatocellular carcinoma aggressiveness".MOLECULAR THERAPY 29.6(2021):2067-2087.