miR-34 is associated with poor prognosis of patients with gallbladder cancer through regulating telomere length in tumor stem cells.
Tumour Biol
; 35(2): 1503-10, 2014 Feb.
Article
em En
| MEDLINE
| ID: mdl-24078448
ABSTRACT
miR-34a has been identified as a tumor suppressor in several tumors, but its involvement in gallbladder cancer (GBC) has not been reported. In this study, the miR-34a level and telomere length were measured in 77 gallbladder adenocarcinomas and 36 peritumoral tissues by real-time PCR. Forced miR-34a expression was established by an adenovirus carrying a miR-34a expression cassette. The colony-forming ability of isolated CD44+CD133+ GBC tumor stem-like cells was measured by matrigel colony assay. The xenograft tumor models were established by inoculating nude mice with CD44+CD133+cells. Results showed that significantly lower miR-34a expression and longer telomere length were observed in gallbladder adenocarcinoma tissues, which correlated with poor prognosis of GBC patients. Forced overexpression of miR-34a inhibited the colony-forming ability of CD44+CD133+ GBC tumor stem-like cells in vitro and xenograft tumor growth in vivo. Injection of Ad-miR-34a downregulated PNUTS expression and reduced telomere length in xenograft GBC tumor cells. In conclusion, miR-34a is a tumor suppressor in gallbladder cancer. Both low miR-34a expression and long telomere length are markers for poor prognosis of patients with gallbladder adenocarcinoma. Our study also suggests that the miR-34a gene could be a target for targeting therapy of GBC.
Buscar no Google
Base de dados:
MEDLINE
Assunto principal:
Adenocarcinoma
/
MicroRNAs
/
Homeostase do Telômero
/
Neoplasias da Vesícula Biliar
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Limite:
Adult
/
Aged
/
Animals
/
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article