KDM6B promotes ESCC cell proliferation and metastasis by facilitating C/EBPß transcription.
BMC Cancer
; 21(1): 559, 2021 May 17.
Article
em En
| MEDLINE
| ID: mdl-34001062
ABSTRACT
BACKGROUND:
As an H3K27me3 demethylase and counteracts polycomb-mediated transcription repression, KDM6B has been implicated in the development and malignant progression in various types of cancers. However, its potential roles in esophageal squamous cell carcinoma (ESCC) have not been explored.METHODS:
The expression of KDM6B in human ESCC tissues and cell lines was examined using RT-qPCR, immunohistochemical staining and immunoblotting. The effects of KDM6B on the proliferation and metastasis of ESCC were examined using in vitro and in vivo functional tests. RNA-seq and ChIP-seq assay were used to demonstrate the molecular biological mechanism of KDM6B in ESCC.RESULTS:
We show that the expression level of KDM6B increased significantly in patients with lymph node metastasis. Furthermore, we confirmed that KDM6B knockdown reduces proliferation and metastasis of ESCC cells, while KDM6B overexpression has the opposite effects. Mechanistically, KDM6B regulates TNFA_SIGNALING_VIA_NFκB signalling pathways, and H3K27me3 binds to the promoter region of C/EBPß, leading to the promotion of C/EBPß transcription. Besides, we show that GSK-J4, a chemical inhibitor of KDM6B, markedly inhibits proliferation and metastasis of ESCC cells.CONCLUSIONS:
The present study demonstrated that KDM6B promotes ESCC progression by increasing the transcriptional activity of C/EBPß depending on its H3K27 demethylase activity.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Esofágicas
/
Regulação Neoplásica da Expressão Gênica
/
Proteína beta Intensificadora de Ligação a CCAAT
/
Histona Desmetilases com o Domínio Jumonji
/
Carcinoma de Células Escamosas do Esôfago
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
/
Male
Idioma:
En
Revista:
BMC Cancer
Assunto da revista:
NEOPLASIAS
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
China
País de publicação:
ENGLAND
/
ESCOCIA
/
GB
/
GREAT BRITAIN
/
INGLATERRA
/
REINO UNIDO
/
SCOTLAND
/
UK
/
UNITED KINGDOM