Human papillomavirus-positivity is associated with EREG down-regulation and promoter hypermethylation in head and neck squamous cell carcinoma.
Exp Mol Pathol
; 117: 104549, 2020 12.
Article
em En
| MEDLINE
| ID: mdl-33007298
ABSTRACT
BACKGROUND:
Human papillomavirus (HPV) etiology has become evident in head and neck cancers (HNCs) and HPV positivity showed a strong association with its malignant progression. Since aberrant DNA methylation is known to drive carcinogenesis and progression in HNCs, we investigated to determine target gene(s) associated with this modification.METHODS:
We characterized epigenetic changes in tumor-related genes (TRGs) that are known to be associated with HNC development and its progression.RESULTS:
The expression levels of 42 candidate HNC-associated genes were analyzed. Of these, 7 TGRs (CHFR, RARß, GRB7, EREG, RUNX2, RUNX3, and SMG-1) showed decreased expressions in HPV-positive (+) HNC cells compared with HPV-negative (-) HNC cells. When gene expression levels were compared corresponding to the DNA methylation conditions, GRB7 and EREG showed significant differential expression between HPV+ and HPV- cells, which suggested these genes as primary targets of epigenetic regulation in HPV-induced carcinogenesis. Furthermore, treatment with a demethylation agent, 5-aza-2'-deoxycytidine (5-aza-dc), caused restoration of EREG expression and was associated with hypomethylation of its promoter in HPV+ cells, while no changes was noted in HPV- cells. EREG promoter hypermethylation in HPV+ cells was confirmed using methylation-specific PCR (MS-PCR).CONCLUSION:
We conclude that EREG is the target of epigenetic regulation in HPV+ HNCs and its suppressed expression through promoter hypermethylation is associated with the development of HPV-associated HNCs.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Epigênese Genética
/
Alphapapillomavirus
/
Epirregulina
/
Carcinoma de Células Escamosas de Cabeça e Pescoço
Tipo de estudo:
Risk_factors_studies
Limite:
Humans
Idioma:
En
Revista:
Exp Mol Pathol
Ano de publicação:
2020
Tipo de documento:
Article