miR-125b functions as a key mediator for snail-induced stem cell propagation and chemoresistance.
J Biol Chem
; 288(6): 4334-45, 2013 Feb 08.
Article
em En
| MEDLINE
| ID: mdl-23255607
ABSTRACT
Chemoresistance is a major obstacle in cancer treatment. Our previous studies have shown that miR-125b plays an important role in chemoresistance. Here we report a novel mechanism that up-regulation of miR-125b through Wnt signaling by Snail enriches cancer stem cells. Overexpression of Snail dramatically increases the expression of miR-125b through the Snail-activated Wnt/ß-catenin/TCF4 axis. Snail confers chemoresistance by repressing Bak1 through up-regulation of miR-125b. Restoring the expression of Bak1 or depleting miR-125b re-sensitizes Snail-expressing cancer cells to Taxol, indicating that miR-125b is critical in Snail-induced chemoresistance. Moreover, overexpression of miR-125b significantly increases the cancer stem cell population (CD24-CD44+), while depletion of miR-125b or rescue of the expression of Bak1 increases the non-stem cell population (CD24+CD44+) in Snail-overexpressing cells. These findings strongly support that miR-125b functions as a key mediator in Snail-induced cancer stem cell enrichment and chemoresistance. This novel mechanism for Snail-induced stem cell propagation and chemoresistance may have important implications in the development of strategies for overcoming cancer cell resistance to chemotherapy.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Fatores de Transcrição
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Células-Tronco Neoplásicas
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RNA Neoplásico
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Resistencia a Medicamentos Antineoplásicos
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MicroRNAs
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Proteínas de Neoplasias
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Neoplasias
Limite:
Humans
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article