CBX3 Regulated By YBX1 Promotes Smoking-induced Pancreatic Cancer Progression via Inhibiting SMURF2 Expression.
Int J Biol Sci
; 18(8): 3484-3497, 2022.
Article
em En
| MEDLINE
| ID: mdl-35637952
ABSTRACT
As a key reversible and heritable mechanism of transcriptional regulation, the epigenetic modification plays a crucial role in tumorigenesis. Of note, tobacco smoking induces epigenetic modifications to promote pancreatic cancer development. Chromobox protein homolog 3 (CBX3) acts as an epigenetic regulator, modulating gene expression of downstream targets via chromatin modifications. To date, the relationship between CBX3 and smoking in pancreatic cancer remains unknown. This study aimed to uncover the specific role and underlying mechanism of CBX3 in smoking-related pancreatic cancer. The bioinformatics analyses were conducted to identify CBX3 as a key player in tobacco-induced pancreatic cancer. The abnormal upregulation of CBX3 was associated with poor prognosis in pancreatic cancer patients. Moreover, cigarette smoke extract (CSE) exposure promoted the overexpression of Y-box-binding protein 1 (YBX1), which consequently led to upregulated CBX3 in pancreatic cancer cells. We also revealed that CBX3 enhanced pancreatic cancer progression, likely by inhibiting the expression of SMAD specific E3 ubiquitin protein ligase 2 (SMURF2) and promoting the activation of TGF-ß signaling. In summary, the YBX1/CBX3/SMURF2 signaling axis may be a promising therapeutic target in patients with smoking-related pancreatic cancer.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Pancreáticas
/
Proteínas Cromossômicas não Histona
/
Ubiquitina-Proteína Ligases
/
Proteína 1 de Ligação a Y-Box
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Int J Biol Sci
Assunto da revista:
BIOLOGIA
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
China