Epigenetic regulation of the extrinsic oncosuppressor PTX3 gene in inflammation and cancer.
Oncoimmunology
; 6(7): e1333215, 2017.
Article
en En
| MEDLINE
| ID: mdl-28811977
ABSTRACT
PTX3 is a component of the humoral arm of innate immunity and an extrinsic oncosuppressor gene taming tumor-promoting inflammation. Here, we show that two enhancers differently regulate PTX3 expression enhancer 1, located 230 kb upstream of PTX3 promoter, mediated the action of inflammatory transcription factors; and enhancer 2, encompassing PTX3 second exon, was implicated in pre-initiation complex assembly. Polycomb repressive complex 2 silenced these regulatory elements and the promoter in basal condition. Enhancer 1 was epigenetically inactivated in early colorectal cancer (CRC) stages, while the promoter and enhancer 2 showed increasingly DNA methylation during CRC progression from adenomas to stage II and III CRC. Inhibition of DNA methylation rescued PTX3 expression in CRC. Finally, enhancer 1 acquired the binding of STAT3 in stage I CRC, and inhibition of STAT3 phosphorylation restored PTX3 activity and decreased enhancer 1 methylation. Thus, the expression of PTX3 is under the control of two enhancers, which emerge as important fine regulators of PTX3 expression in inflammation and cancer.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Idioma:
En
Revista:
Oncoimmunology
Año:
2017
Tipo del documento:
Article
País de afiliación:
Italia