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.
Article
in English
| 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.
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Phosphorylation
/
Prognosis
/
Biliary Tract
/
Biliary Tract Neoplasms
/
In Vitro Techniques
/
DNA Damage
/
Transfection
/
Cell Line
/
Cisplatin
/
RNA, Small Interfering
Type of study:
Prognostic study
Limits:
Animals
/
Humans
Language:
English
Journal:
Cancer Research and Treatment
Year:
2019
Type:
Article
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