MicroRNA-21 suppression impedes medulloblastoma cell migration.
Eur J Cancer
; 47(16): 2479-90, 2011 Nov.
Article
en En
| MEDLINE
| ID: mdl-21775132
ABSTRACT
Medulloblastoma (MB), the most common malignant brain tumour in children, is characterised by a high risk of leptomeningeal dissemination. But little is known about the molecular mechanisms that promote cancer cell migration in MB. Aberrant expression of miR-21 is recognised to be causatively linked to metastasis in a variety of human neoplasms including brain tumours; however its function in MB is still unknown. In this study we investigated the expression level and the role of miR-21 in MB cell migration. miR-21 was found to be up-regulated, compared to normal cerebellum, in 29/29 MB primary samples and 6/6 MB-derived cell lines. Inverse correlation was observed between miR-21 expression and the metastasis suppressor PDCD4, while miR-21 repression increased the release of PDCD4 protein, suggesting negative regulation of PDCD4 by miR-21 in MB cells. Anti-miR-21 decreased protein expression of the tumour cell invasion mediators MAP4K1 and JNK, which are also known to be negatively regulated by PDCD4, and down-regulated integrin protein that is essential for MB leptomeningeal dissemination. Moreover miR-21 knockdown in MB cells increased the expression of two eminent negative modulators of cancer cell migration, E-Cadherin and TIMP2 proteins that are known to be positively regulated by PDCD4. Finally and importantly, suppression of miR-21 decreased the motility of MB cells and reduced their migration across basement membranes in vitro. Together, these compelling data propose miR-21 pathway as a novel mechanism impacting MB cell dissemination and raises the possibility that curability of selected MB may be improved by pharmaceutical strategies directed towards microRNA-21.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Contexto en salud:
2_ODS3
/
6_ODS3_enfermedades_notrasmisibles
/
7_ODS3_muertes_prevenibles_nacidos_ninos
Problema de salud:
2_muertes_prevenibles
/
6_brain_nervous_system_cancer
/
7_neonatal_care_health
/
7_non_communicable_diseases
Asunto principal:
ARN Neoplásico
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Inhibición de Migración Celular
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Neoplasias Cerebelosas
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MicroARNs
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Meduloblastoma
Límite:
Adolescent
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Adult
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Child
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Child, preschool
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Female
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Humans
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Infant
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Male
Idioma:
En
Revista:
Eur J Cancer
Año:
2011
Tipo del documento:
Article
País de afiliación:
Suiza