NEK2 promotes proliferation, migration and tumor growth of gastric cancer cells via regulating KDM5B/H3K4me3

	NEK2 promotes proliferation, migration and tumor growth of gastric cancer cells via regulating KDM5B/H3K4me3
	Li, Yiwei 2; Chen, Lijuan 2; Feng, Lixing 2; Zhu, Mengli 2; Shen, Qiang 3; Fang, Yanfen 1,2; Liu, Xuan 3; Zhang, Xiongwen 2
刊名	AMERICAN JOURNAL OF CANCER RESEARCH
	2019
卷号	9 期号:11 页码:2364-2378
关键词	Gastric cancer NEK2 KDM5B beta-catenin c-Myc
ISSN号	2156-6976
通讯作者	Fang, Yanfen(yffang@simm.ac.cn) ; Liu, Xuan(xuanliu@shutcm.edu.cn) ; Zhang, Xiongwen(xwzhang@sat.ecnu.edu.cn)
英文摘要	The mechanisms of how Never in Mitosis (NIMA) Related Kinase 2 (NEK2) coordinates altered signaling to malignant gastric cancer (GC) transformation remain unclear. Overexpression of NEK2 and KDM5B were observed in GC cell lines with high sensitivity to NEK2 inhibitors. Here we investigated the biological behaviors of NEK2 and the possible mechanisms of regulative effects of NEK2 on KDM5B in GC cell lines both in vitro and in vivo. The results showed that NEK2 and KDM5B were highly expressed in most of the 10 GC cell lines. NEK2 knockdown in MGC-803 cells led to suppression of cell proliferation and migration in vitro and tumor growth in vivo, while NEK2 overexpression in BGC-823 cells exhibited the reverse biological effect. When NEK2 was inhibited by NEK2 inhibitors or shNEK2, cellular KDM5B level decreased and H3K4me3 level increased, while overexpression of NEK2 resulted in enhanced KDM5B expression and decreased H3K4me3 level. Though direct interaction between NEK2 and KDM5B was excluded, NEK2 could regulate KDM5B/H3K4me3 expression through beta-catenin/Myc both in vitro and in vivo, which was double confirmed by c-myc and KDM5B inhibitor experiments. Taken together, our study showed that NEK2 was highly expressed in GC cell lines and related to promoting cell proliferation, migration and tumor growth. A NEK2/beta-catenin/Myc/KDM5B/H3K4me3 signaling pathway may contribute to the important carcinogenic role of NEK2-mediated malignant behaviors in GC.
资助项目	National Nature Science Foundation of China[81873056] ; National Nature Science Foundation of China[81872496] ; National Nature Science Foundation of China[21572263] ; National Nature Science Foundation of China[21572067] ; pilot project of the Chinese academy of sciences[XDA12020356] ; Open Project of the State Key Laboratory of Innovative Natural Medicine and Traditional Chinese Medicine Injections[QFSKL2018006] ; Shanghai Planned Projects for Postdoctoral Research Funds[14R214-10700]
WOS关键词	BETA-CATENIN ; DRUG-RESISTANCE ; PROTEIN-KINASE ; NIMA FAMILY ; INHIBITORS ; MYC ; DEMETHYLASES ; PROGRESSION ; EXPRESSION ; MEMBER
WOS研究方向	Oncology
语种	英语
出版者	E-CENTURY PUBLISHING CORP
WOS记录号	WOS:000500293000006
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/282069]
专题	中国科学院上海药物研究所
通讯作者	Fang, Yanfen; Liu, Xuan; Zhang, Xiongwen
作者单位	1.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Div Antitumor Pharmacol, Shanghai 201203, Peoples R China 2.East China Normal Univ, Sch Chem & Mol Engn, Shanghai Engn Res Ctr Mol Therapeut & New Drug De, Shanghai 200062, Peoples R China 3.Shanghai Univ Tradit Chinese Med, Inst Interdisciplinary Integrat Biomed Res, Shanghai 201203, Peoples R China
推荐引用方式 GB/T 7714	Li, Yiwei,Chen, Lijuan,Feng, Lixing,et al. NEK2 promotes proliferation, migration and tumor growth of gastric cancer cells via regulating KDM5B/H3K4me3[J]. AMERICAN JOURNAL OF CANCER RESEARCH,2019,9(11):2364-2378.
APA	Li, Yiwei.,Chen, Lijuan.,Feng, Lixing.,Zhu, Mengli.,Shen, Qiang.,...&Zhang, Xiongwen.(2019).NEK2 promotes proliferation, migration and tumor growth of gastric cancer cells via regulating KDM5B/H3K4me3.AMERICAN JOURNAL OF CANCER RESEARCH,9(11),2364-2378.
MLA	Li, Yiwei,et al."NEK2 promotes proliferation, migration and tumor growth of gastric cancer cells via regulating KDM5B/H3K4me3".AMERICAN JOURNAL OF CANCER RESEARCH 9.11(2019):2364-2378.