Jab1 Silencing Inhibits Proliferation and Sensitizes to Cisplatin in Biliary Tract Cancer / Journal of the Korean Cancer Association, 대한암학회지
Cancer Research and Treatment
;
: 886-900, 2019.
Artigo
em Inglês
| WPRIM
| ID: wpr-763190
ABSTRACT
PURPOSE:
Jab1 is a coactivator of c-Jun that enhances the transcriptional function of c-Jun. Jab1 is frequently overexpressed in various cancers and is associatedwith poor prognosis of cancer patients. Thus, Jab1 could be a potential therapeutic target in cancer. However, the role of Jab1 in biliary tract cancer (BTC) has not been studied. MATERIALS ANDMETHODS:
We performed in vitro and in vivo experiments to evaluate the therapeutic potential ofJab1 inhibition in BTC.RESULTS:
Among 8 BTC cell lines, many showed higher Jab1 expression levels. In addition, Jab1 silencing by siRNA increased p27 expression levels. SNU478 and HuCCT-1 cells exhibited profound Jab1 knockdown and increased p27 expression by Jab1-specific siRNA transfection. Jab1 silencing induced anti-proliferative and anti-migratory effects and resulted in G1 cell cycle arrest in SNU478 and HuCCT-1 cells. In addition, Jab1 silencing potentiated the anti-proliferative and anti-migratory effects of cisplatin by increasing DNA damage. Interestingly,Jab1 knockdown increased PTEN protein half-life, resulting in increased PTEN expression. In the HuCCT-1 mouse xenograft model, stable knockdown of Jab1 by shRNA also showed anti-proliferative effects in vivo, with decreased Ki-67 expression and AKT phosphorylation and increased Terminal deoxynucleotidyl transferase–mediated dUTP nick end labeling and p27 expression.CONCLUSION:
Jab1 knockdown demonstrated anti-proliferative and anti-migratory effects in BTC cells by increasing DNA damage and stabilizing PTEN, resulting in G1 cell cycle arrest. In addition, Jab1 silencing potentiated the anti-proliferative effects of cisplatin. Our data suggest that Jab1 may be a potential therapeutic target in BTC that is worthy of further investigations.
Texto completo:
DisponíveL
Índice:
WPRIM (Pacífico Ocidental)
Assunto principal:
Fosforilação
/
Prognóstico
/
Sistema Biliar
/
Neoplasias do Sistema Biliar
/
Técnicas In Vitro
/
Dano ao DNA
/
Transfecção
/
Linhagem Celular
/
Cisplatino
/
RNA Interferente Pequeno
Tipo de estudo:
Estudo prognóstico
Limite:
Animais
/
Humanos
Idioma:
Inglês
Revista:
Cancer Research and Treatment
Ano de publicação:
2019
Tipo de documento:
Artigo
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