Open AccessEXT1 methylation promotes proliferation and migration and predicts the clinical outcome of non‐small cell lung carcinoma via WNT signalling pathway
Author(s) -
Kong Wencui,
Chen Ying,
Zhao Zhongquan,
Zhang Lei,
Lin Xiandong,
Luo Xingguang,
Wang Shuiliang,
Song Zhengbo,
Lin Xiangwu,
Lai Guoxiang,
Yu Zongyang
Publication year - 2021
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.16277
Subject(s) - wnt signaling pathway , dna methylation , methylation , cancer research , biology , lrp6 , cell growth , cell migration , gene expression , regulation of gene expression , gene , cell , genetics
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.