EXT1 methylation promotes proliferation and migration and predicts the clinical outcome of non-small cell lung carcinoma via WNT signalling pathway

doi:10.1111/jcmm.16277

	EXT1 methylation promotes proliferation and migration and predicts the clinical outcome of non-small cell lung carcinoma via WNT signalling pathway
	Kong, Wencui 2; Chen, Ying 2; Zhao, Zhongquan 2; Zhang, Lei 2; Lin, Xiandong 3,4; Luo, Xingguang 5; Wang, Shuiliang 1,6; Song, Zhengbo 7,8,9; Lin, Xiangwu 10; Lai, Guoxiang 2
刊名	JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
	2021-03-01
卷号	25
关键词	DNA methylation EXT1 migration prognosis proliferation WNT
ISSN号	1582-1838
DOI	10.1111/jcmm.16277
通讯作者	Lai, Guoxiang(laiguoxiang2007@163.com) ; Yu, Zongyang(yuzfuzhou@163.com)
英文摘要	DNA methylation is important for lung cancer prognosis. In this work, it is aimed to seek novel biomarkers with DNA methylation-expression-pathway pattern and explore its underlying mechanism. Prognostic DNA methylation sites and mRNAs were screened in NSCLC data set from TCGA, and further validated using the samples retrospectively collected, and EXT1 was identified as a potential target. Gene body methylation of three CpG sites (cg03276982, cg11592677, cg16286281) on EXT1 was significantly associated with clinical outcome, and the EXT1 gene expression also predicted prognosis. The expression level of EXT1 was also correlated with its DNA methylation level. This observation was further validated in a new data set consist of 170 samples. Knocking down of EXT1 resulted in decreased proliferation and migration. EXT1 targets were analysed using GSEA. It is found that the WNT signalling is the potential downstream target of EXT1. Further analyses revealed that the EXT1 targets the beta-catenin and effect migration rate of NSCLC cell lines. The WNT signalling inhibitor, XAV-939, effectively disrupted the migration promotion effect induced by EXT1. In summary, EXT1 methylation regulates the gene expression, effects the proliferation and migration via WNT pathway and predicted a poor prognosis for NSCLC.
资助项目	Science and Technology Major Project of Fujian Province[2017YZ0001-2] ; Fujian Province[2017Y9127]
WOS研究方向	Cell Biology ; Research & Experimental Medicine
语种	英语
出版者	WILEY
WOS记录号	WOS:000616419400001
资助机构	Science and Technology Major Project of Fujian Province ; Fujian Province
内容类型	期刊论文
源URL	[http://ir.hfcas.ac.cn:8080/handle/334002/120658]
专题	中国科学院合肥物质科学研究院
通讯作者	Lai, Guoxiang; Yu, Zongyang
作者单位	1.Fujian Med Univ, Dept Urol, 900th Hosp Joint Logist Team Support Force, Fuzhou, Peoples R China 2.PLA, Dept Resp Med & Crit Care Med, 900th Hosp Joint Logist Support Force, 156 Xierhuan North Rd, Fuzhou 350025, Peoples R China 3.Fujian Canc Hosp, Lab Radiat Oncol & Radiobiol, Fuzhou, Peoples R China 4.Fujian Med Univ, Canc Hosp, Fuzhou, Peoples R China 5.Yale Univ, Sch Med, Div Human Genet, Dept Psychiat, West Haven, CT 06516 USA 6.Xiamen Univ, Affiliated Dongfang Hosp, Fujian Key Lab Transplant Biol, Sch Med, Fuzhou, Peoples R China 7.Chinese Acad Sci, Inst Canc & Basic Med, Hangzhou, Peoples R China 8.Univ Chinese Acad Sci, Dept Med Oncol, Canc Hosp, Hangzhou, Peoples R China 9.Zhejiang Canc Hosp, Dept Med Oncol, Hangzhou, Peoples R China 10.PLA, Med Oncol, 900th Hosp Joint Logist Support Force, Fuzhou, Peoples R China
推荐引用方式 GB/T 7714	Kong, Wencui,Chen, Ying,Zhao, Zhongquan,et al. EXT1 methylation promotes proliferation and migration and predicts the clinical outcome of non-small cell lung carcinoma via WNT signalling pathway[J]. JOURNAL OF CELLULAR AND MOLECULAR MEDICINE,2021,25.
APA	Kong, Wencui.,Chen, Ying.,Zhao, Zhongquan.,Zhang, Lei.,Lin, Xiandong.,...&Yu, Zongyang.(2021).EXT1 methylation promotes proliferation and migration and predicts the clinical outcome of non-small cell lung carcinoma via WNT signalling pathway.JOURNAL OF CELLULAR AND MOLECULAR MEDICINE,25.
MLA	Kong, Wencui,et al."EXT1 methylation promotes proliferation and migration and predicts the clinical outcome of non-small cell lung carcinoma via WNT signalling pathway".JOURNAL OF CELLULAR AND MOLECULAR MEDICINE 25(2021).