hsa-mir183/EGR1-mediated regulation of E2F1 is required for CML stem/progenitor cell survival.
Blood
; 131(14): 1532-1544, 2018 04 05.
Article
em En
| MEDLINE
| ID: mdl-29437554
ABSTRACT
Chronic myeloid leukemia (CML) stem/progenitor cells (SPCs) express a transcriptional program characteristic of proliferation, yet can achieve and maintain quiescence. Understanding the mechanisms by which leukemic SPCs maintain quiescence will help to clarify how they persist during long-term targeted treatment. We have identified a novel BCR-ABL1 protein kinase-dependent pathway mediated by the upregulation of hsa-mir183, the downregulation of its direct target early growth response 1 (EGR1), and, as a consequence, upregulation of E2F1. We show here that inhibition of hsa-mir183 reduced proliferation and impaired colony formation of CML SPCs. Downstream of this, inhibition of E2F1 also reduced proliferation of CML SPCs, leading to p53-mediated apoptosis. In addition, we demonstrate that E2F1 plays a pivotal role in regulating CML SPC proliferation status. Thus, for the first time, we highlight the mechanism of hsa-mir183/EGR1-mediated E2F1 regulation and demonstrate this axis as a novel, critical factor for CML SPC survival, offering new insights into leukemic stem cell eradication.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Células-Tronco Neoplásicas
/
RNA Neoplásico
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Leucemia Mielogênica Crônica BCR-ABL Positiva
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Regulação Leucêmica da Expressão Gênica
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Regulação para Cima
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MicroRNAs
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Proteína 1 de Resposta de Crescimento Precoce
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Fator de Transcrição E2F1
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Proteínas de Neoplasias
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Female
/
Humans
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Male
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article