MiR-139 inhibits Mcl-1 expression and potentiates TMZ-induced apoptosis in glioma.
CNS Neurosci Ther
; 19(7): 477-83, 2013 Jul.
Article
em En
| MEDLINE
| ID: mdl-23551751
ABSTRACT
AIMS:
Mcl-1, an antiapoptotic member of the Bcl-2 family, is overexpressed in human glioblastoma, conferring a survival advantage to tumor cells. The mechanisms underlying its dysregulation have not been clarified. In this study, we explored the involvement of micro-RNAs that acted as endogenous sequence-specific suppressors of gene expression. METHODS ANDRESULTS:
Using computational and TCGA analysis, we identified miR-139 as being downregulated in glioblastoma in comparison with human brain tissue, as well as possessing a putative target site in Mcl-1 mRNA. Overexpression of miR-139 led to a clear decrease in Mcl-1 expression in gliomas. Reporter assays revealed direct post-transcriptional regulation involving miR-139 and the 3'-untranslated region of Mcl-1. Human glioma tissues with low expression of miR-139 displayed higher expression of Mcl-1 protein than those with high expression, suggesting that low miR-139 contributes to Mcl-1 overexpression. In addition, upregulation of miR-139 suppressed the proliferation and enhanced temozolomide (TMZ)-induced apoptosis. Finally, we observed that Mcl-1 knockdown resulted in similar effects compared with miR-139 transfection.CONCLUSION:
Our results suggested that miR-139 negatively regulated Mcl-1 and induced apoptosis in cooperation with an anticancer drug TMZ in glioma.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Encefálicas
/
Apoptose
/
Antineoplásicos Alquilantes
/
Dacarbazina
/
MicroRNAs
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Proteína de Sequência 1 de Leucemia de Células Mieloides
/
Glioma
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
CNS Neurosci Ther
Assunto da revista:
NEUROLOGIA
/
TERAPEUTICA
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
China