KAT5 silencing induces apoptosis of GBC-SD cells through p38MAPK-mediated upregulation of cleaved Casp9.
Int J Clin Exp Pathol
; 7(1): 80-91, 2014.
Article
in En
| MEDLINE
| ID: mdl-24427328
ABSTRACT
The poor overall prognosis of Gallbladder carcinoma (GBC) patients and the limited therapeutic regimens for these patients demonstrates the need for better therapeutic modalities, while the growing evidences have indicated that those genes contributed to epigenetic regulation may serve as therapeutic targets. The function of histone acetylation on growth and survival of GBC cells remains unknown. In present study, an RNAi screening of 16 genes involving histone acetyltransferases (HATs) was applied to GBC-SD cells and we found that KAT5 knockdown specifically inhibits the proliferation of GBC-SD cells by casp9-mediated apoptosis. Microarray data analysis showed that KAT5 RNAi may result in cleaved casp9 upregulation through p38MAPK activation in GBC-SD cells. The mRNA expression level of KAT5 was significantly upregulated in GBC tissues than in the adjacent normal tissues. In consistence with the mRNA level, the protein expression of KAT5 was markedly increased in tissues from patients with poor prognosis than those with good prognosis. These findings strongly indicated that KAT5 was implicated in GBC tumorigenesis and that its expression level was associated with the prognosis. Our work may also provide a potential therapeutic target for treatment of GBC patients.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Gene Expression Regulation, Neoplastic
/
P38 Mitogen-Activated Protein Kinases
/
Histone Acetyltransferases
/
Caspase 9
/
Gallbladder Neoplasms
Type of study:
Prognostic_studies
Limits:
Humans
Language:
En
Journal:
Int J Clin Exp Pathol
Journal subject:
PATOLOGIA
Year:
2014
Document type:
Article
Affiliation country:
China