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Identification of new hypoxia‐regulated epithelial‐mesenchymal transition marker genes labeled by H3K4 acetylation
Author(s) -
Wang JianQiu,
Yan FengQin,
Wang LiHui,
Yin WenJuan,
Chang TingYu,
Liu JunPing,
Wu KouJuey
Publication year - 2020
Publication title -
genes, chromosomes and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.754
H-Index - 119
eISSN - 1098-2264
pISSN - 1045-2257
DOI - 10.1002/gcc.22802
Subject(s) - epithelial–mesenchymal transition , cancer research , chromatin immunoprecipitation , biology , microbiology and biotechnology , histone deacetylase , histone h3 , gene knockdown , cdh1 , chromatin , chromatin remodeling , histone , gene , promoter , gene expression , transition (genetics) , cell , genetics , cadherin
Abstract Hypoxia‐induced epithelial‐mesenchymal transition (EMT) involves the interplay between chromatin modifiers histone deacetylase 3 (HDAC3) and WDR5. The histone mark histone 3 lysine 4 acetylation (H3K4Ac) is observed in the promoter regions of various EMT marker genes (eg, CDH1 and VIM ). To further define the genome‐wide location of H3K4Ac, a chromatin immunoprecipitation followed by massively parallel DNA sequencing (ChIP‐seq) analysis was performed using a head and neck squamous cell carcinoma (HNSCC) FaDu cell line under normoxia and hypoxia. H3K4Ac was found to be located mainly around the transcription start site. Coupled with analysis of gene expression by RNA sequencing and using a HDAC3 knockdown cell line, 10 new genes ( BMI1 , GLI1 , SMO , FOXF1 , SIRT2 , etc) that were labeled by H3K4Ac and regulated by HDAC3 were identified. Overexpression or knockdown of GLI1/SMO increased or repressed the in vitro migration and invasion activity in OECM‐1/FaDu cells, respectively. In HNSCC patients, coexpression of GLI1 and SMO in primary tumors correlated with metastasis. Our results identify new EMT marker genes that may play a significant role in hypoxia‐induced EMT and metastasis and further provide diagnostic and prognostic implications.