Identification of new hypoxia-regulated epithelial-mesenchymal transition marker genes labeled by H3K4 acetylation

Jian Qiu Wang, Feng Qin Yan, Li Hui Wang, Wen Juan Yin, Ting Yu Chang, Jun Ping Liu, Kou Juey Wu*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

21 Scopus citations

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.

Original languageEnglish
Pages (from-to)73-83
Number of pages11
JournalGenes Chromosomes and Cancer
Volume59
Issue number2
DOIs
StatePublished - 01 02 2020

Bibliographical note

Publisher Copyright:
© 2019 Wiley Periodicals, Inc.

Keywords

  • H3K4Ac
  • HDAC3
  • epithelial-mesenchymal transition
  • hypoxia
  • metastasis

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