南方科技大学知识苑(SUSTech KC): Notch activation suppresses endothelial cell migration and sprouting via miR-223-3p targeting Fbxw7

题名	Notch activation suppresses endothelial cell migration and sprouting via miR-223-3p targeting Fbxw7
作者	Wang, Ruonan 1,2; Yang, Ziyan 2; Liang, Liang 2; Feng, Xingxing 1,2; Che, Bo 1,2; Zhang, Xiaoyan 2; Zheng, Qijun 3,4; Yan, Xianchun 2; Han, Hua 2
通讯作者	Zheng, Qijun; Yan, Xianchun; Han, Hua
发表日期	2022-02-01
DOI	10.1007/s11626-022-00649-y
发表期刊	IN VITRO CELLULAR & DEVELOPMENTAL BIOLOGY-ANIMAL 影响因子和分区
ISSN	1071-2690
EISSN	1543-706X
摘要	Angiogenesis involves temporo-spatially coordinated endothelial cell (EC) proliferation, differentiation, migration, and sprouting. Notch signaling is essential in regulating EC behaviors during angiogenesis, but its downstream mechanisms remain incompletely defined. In the current study, we show that miR-223-3p is a downstream molecule of Notch signaling and mediates the role of Notch signaling in regulating EC migration and sprouting. In human umbilical vein endothelial cells (HUVECs), Notch activation by immobilized Dll4, a Notch ligand, upregulated miR-223-3p, and Notch activation-mediated miR-223-3p upregulation could be blocked by a gamma-secretase inhibitor (DAPT). miR-223-3p overexpression apparently repressed HUVEC migration, leading to attenuated lumen formation and sprouting capacities. Transcriptome comparison and subsequent qRT-PCR validation further indicated that miR-223-3p downregulated the expression of multiple genes involved in EC migration, axon guidance, extracellular matrix remodeling, and angiogenesis. In addition, miR-223-3p antagonist transfection abolished Notch-mediated repression of EC migration and sprouting. By quantitative reverse transcription-polymerase chain reaction (qRT-PCR), western blotting, and reporter assay analysis, we confirmed that miR-223-3p directly targeted F-box and WD repeat domain-containing 7 (Fbxw7). Meanwhile, Fbxw7 overexpression could efficiently rescue the impaired migration capacity of ECs under miR-223-3p overexpression. In summary, these results identify that Notch activation-induced miR-223-3p suppresses EC migration and sprouting via Fbxw7.
关键词	Notch miR-223-3p Endothelial cells Migration Angiogenesis
相关链接	[来源记录]
收录类别	SCI
语种	英语
学校署名	通讯
资助项目	National Natural Science Foundation of China[31671523,31730041,82003110] ; Natural Science Foundation of Shaanxi Province[2020JQ-441]
WOS研究方向	Cell Biology ; Developmental Biology
WOS类目	Cell Biology ; Developmental Biology
WOS记录号	WOS:000759370500001
出版者	SPRINGER
ESI学科分类	MOLECULAR BIOLOGY & GENETICS
来源库	Web of Science
引用统计	被引频次[WOS]：7
成果类型	期刊论文
条目标识符	http://sustech.caswiz.com/handle/2SGJ60CL/291080
专题	南方科技大学第一附属医院
作者单位	1.Northwest Univ, Fac Life Sci, Xian 710069, Peoples R China 2.Fourth Mil Med Univ, State Key Lab Canc Biol, Dept Biochem & Mol Biol, Chang Le Xi St 169, Xian 710032, Peoples R China 3.Jinan Univ, Sch Clin Med 2, Shenzhen Peoples Hosp, Dept Cardiovasc Surg, Jinan, Peoples R China 4.Southern Univ Sci & Technol, Affiliated Hosp 1, Shenzhen 518020, Peoples R China
通讯作者单位	南方科技大学第一附属医院
推荐引用方式 GB/T 7714	Wang, Ruonan,Yang, Ziyan,Liang, Liang,et al. Notch activation suppresses endothelial cell migration and sprouting via miR-223-3p targeting Fbxw7[J]. IN VITRO CELLULAR & DEVELOPMENTAL BIOLOGY-ANIMAL,2022.
APA	Wang, Ruonan.,Yang, Ziyan.,Liang, Liang.,Feng, Xingxing.,Che, Bo.,...&Han, Hua.(2022).Notch activation suppresses endothelial cell migration and sprouting via miR-223-3p targeting Fbxw7.IN VITRO CELLULAR & DEVELOPMENTAL BIOLOGY-ANIMAL.
MLA	Wang, Ruonan,et al."Notch activation suppresses endothelial cell migration and sprouting via miR-223-3p targeting Fbxw7".IN VITRO CELLULAR & DEVELOPMENTAL BIOLOGY-ANIMAL (2022).