Cullin-7 (CUL7) is overexpressed in glioma cells and promotes tumorigenesis via NF-kappa B activation

doi:10.1186/s13046-020-01553-7

科研成果详情

题名	Cullin-7 (CUL7) is overexpressed in glioma cells and promotes tumorigenesis via NF-kappa B activation
作者	Xu, Jianye 1,2,3; Zhang, Zongpu 1,2,3; Qian, Mingyu 1,2,3; Wang, Shaobo 1,2,3; Qiu, Wei 1,2,3; Chen, Zihang 1,2,3; Sun, Zhongzheng 1,2,3,4; Xiong, Ye1,2,3,5; Wang, Chaochao 1,2,3,6; Sun, Xiaopeng 1,2,3,7; Zhao, Rongrong 1,2,3; Xue, Hao 1,2,3; Li, Gang 1,2,3
发表日期	2020-04-06
发表期刊	JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH 影响因子和分区
语种	英语
原始文献类型	Article
关键词	CUL7 Glioma NF-kappa B MST1 miR-3940-5p
其他关键词	MESENCHYMAL TRANSITION ; POOR-PROGNOSIS ; CANCER CELLS ; LUNG-CANCER ; GLIOBLASTOMA ; PROLIFERATION ; INVASION ; SUBTYPE ; MST1 ; MIR-3940-5P
摘要	Background Cullin-7 (CUL7) is a member of the DOC domain-containing cullin family and is involved in the regulation of cell transformation. However, the clinical significance, potential mechanism and upstream regulators of CUL7 in malignant gliomas remain to be determined. Methods Expression level data and clinical information were obtained via the Cancer Genome Atlas (TCGA) database, the Chinese Glioma Genome Atlas (CGGA) database, immunohistochemistry (IHC) and western blot analysis. Gene set enrichment analysis (GSEA) was used to explore the potential molecular mechanisms of CUL7. RNA silencing was performed using siRNA or lentiviral constructs in U87MG and U251 glioma cell lines and GSC267 glioma stem cells. CUL7 overexpression was performed using the GV141-CUL7 plasmid construct. In addition, overexpression of miR-3940-5p was performed and validated by quantitative real-time PCR (qRT-PCR). Cells were characterized in vitro or in vivo to evaluate their molecular status, cell proliferation, invasion, and migration by Cell Counting Kit (CCK)-8, EdU, flow cytometry, colony formation, Transwell and 3D tumour spheroid invasion assays. Coimmunoprecipitation (co-IP) and western blotting were performed to test the mechanisms of activation of the NF-kappa B signalling pathway. Results High CUL7 expression was associated with a high tumour grade, a mesenchymal molecular glioma subtype and a poor prognosis in patients. Gene silencing of CUL7 in U87MG and U251 cells significantly inhibited tumour growth, invasion and migration in vitro and in vivo. Western blot analysis revealed that cyclin-dependent kinase inhibitors and epithelial-mesenchymal transition (EMT) molecular markers changed under CUL7 silencing conditions. In contrast, CUL7 overexpression promoted tumour growth, invasion and migration. Gene set enrichment analysis (GSEA) and western blot analysis revealed that CUL7 was positively associated with the NF-kappa B pathway. Moreover, with coimmunoprecipitation assays, we discovered that CUL7 physically associated with MST1, which further led to ubiquitin-mediated MST1 protein degradation, which promoted activation of the NF-kappa B signalling pathway. Finally, CUL7 was found to be downregulated by miR-3940-5p, which suppressed the development of gliomas. Conclusions Our findings indicate that CUL7 plays a significant role in promoting tumorigenesis via NF-kappa B activation and that it can be negatively regulated by miR-3940-5p in human gliomas. Furthermore, CUL7 might be a candidate molecular target for the treatment of glioma.
资助项目	National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81571284, 81874083, 81702468, 81802966, 81902540]; National Natural Science Foundation of Shandong Province of China [2017CXGC1203, 2017G006012, ZR2019BH057]; Taishan Scholars of Shandong Province of China [ts201511093]
出版者	BMC
出版地	LONDON
ISSN	1756-9966
EISSN	1756-9966
卷号	39 期号:1 页码:59
DOI	10.1186/s13046-020-01553-7
页数	21
WOS类目	Oncology
WOS研究方向	Oncology
WOS记录号	WOS:000525296300001
收录类别	SCIE ; PUBMED ; SCOPUS
URL	查看原文
Pubmed记录号	32252802
PMC记录号	PMC7132976
Scopus记录号	2-s2.0-85083071228
通讯作者地址	[Xue, Hao]Department of Neurosurgery,Qilu Hospital,Shandong University,107 Wenhua Xi Road,Jinan Shandong Province,250012,China
scopus学科分类	Oncology;Cancer Research
引用统计	被引频次：28[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/8650
专题	附属第一医院_神经外科
通讯作者	Xue, Hao
作者单位	1.Department of Neurosurgery,Qilu Hospital,Shandong University,107 Wenhua Xi Road,Jinan Shandong Province,250012,China; 2.Institute of Brain and Brain-Inspired Science,Shandong University,107 Wenhua Xi Road,Jinan Shandong Province,250012,China; 3.Shandong Key Laboratory of Brain Function Remodeling,Shandong University,107 Wenhua Xi Road,Jinan Shandong Province,250012,China; 4.Department of Neurosurgery,Second Hospital,Shandong University,#247 Beiyuan Street,Jinan,250033,China; 5.Department of Neurosurgery,First Affiliated Hospital,Wenzhou Medical University,Fanhai Xi Road,Wenzhou,325000,China; 6.Department of Neurosurgery,Qilu Hospital,Shandong University (Qingdao),#758 Hefei Road,Qingdao,266035,China; 7.Department of Neurosurgery,Dezhou People's Hospital,#1751 XinhuStreet,Dezhou,253014,China
推荐引用方式 GB/T 7714	Xu, Jianye,Zhang, Zongpu,Qian, Mingyu,et al. Cullin-7 (CUL7) is overexpressed in glioma cells and promotes tumorigenesis via NF-kappa B activation[J]. JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH,2020,39(1):59.
APA	Xu, Jianye., Zhang, Zongpu., Qian, Mingyu., Wang, Shaobo., Qiu, Wei., ... & Li, Gang. (2020). Cullin-7 (CUL7) is overexpressed in glioma cells and promotes tumorigenesis via NF-kappa B activation. JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH, 39(1), 59.
MLA	Xu, Jianye,et al."Cullin-7 (CUL7) is overexpressed in glioma cells and promotes tumorigenesis via NF-kappa B activation".JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH 39.1(2020):59.