Involvement of miR17 pathway in glucocorticoid-induced cell death in pediatric acute lymphoblastic leukemia.
Leuk Lymphoma
; 53(10): 2041-50, 2012 Oct.
Article
en En
| MEDLINE
| ID: mdl-22475310
ABSTRACT
Analysis of the microRNA transcriptome following dexa- methasone treatment of the acute lymphocytic leukemia (ALL) cell line RS4;11 showed a global down-regulation of microRNA levels. MIR17HG was rapidly down-regulated following treatment, with chromatin immunoprecipitation (ChIP) analysis demonstrating the promoter to be a direct target of glucocorticoid (GC)-transcriptional repression and revealing the miR17-92 cluster as a prime target for dexamethasone-induced repression. The loss of miR17 family expression and concomitant increases in the miR17 target Bim occurred in an additional ALL cell line SUP-B15 but not in the dexamethasone-resistant REH. Alteration of miR17 levels through up-regulation or inhibition resulted in an decrease and increase, respectively, in Bim protein levels and dexamethasone-induced cell death. Primary ex vivo ALL cells that underwent apoptosis induced by dexamethasone also down-regulated miR17 levels. Thus, down-regulation of miR17 plays an important role in glucocorticoid-induced cell death suggesting that targeting miR17 may improve the current ALL combination therapy.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Contexto en salud:
6_ODS3_enfermedades_notrasmisibles
Problema de salud:
6_leukemia
Asunto principal:
Transducción de Señal
/
Apoptosis
/
MicroARNs
/
Leucemia-Linfoma Linfoblástico de Células Precursoras
/
Glucocorticoides
Límite:
Child
/
Humans
Idioma:
En
Revista:
Leuk Lymphoma
Asunto de la revista:
HEMATOLOGIA
/
NEOPLASIAS
Año:
2012
Tipo del documento:
Article
País de afiliación:
Suecia