Multiple mechanisms disrupt the let-7 microRNA family in neuroblastoma.
Nature
; 535(7611): 246-51, 2016 07 14.
Article
en En
| MEDLINE
| ID: mdl-27383785
ABSTRACT
Poor prognosis in neuroblastoma is associated with genetic amplification of MYCN. MYCN is itself a target of let-7, a tumour suppressor family of microRNAs implicated in numerous cancers. LIN28B, an inhibitor of let-7 biogenesis, is overexpressed in neuroblastoma and has been reported to regulate MYCN. Here we show, however, that LIN28B is dispensable in MYCN-amplified neuroblastoma cell lines, despite de-repression of let-7. We further demonstrate that MYCN messenger RNA levels in amplified disease are exceptionally high and sufficient to sponge let-7, which reconciles the dispensability of LIN28B. We found that genetic loss of let-7 is common in neuroblastoma, inversely associated with MYCN amplification, and independently associated with poor outcomes, providing a rationale for chromosomal loss patterns in neuroblastoma. We propose that let-7 disruption by LIN28B, MYCN sponging, or genetic loss is a unifying mechanism of neuroblastoma development with broad implications for cancer pathogenesis.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Proteínas Nucleares
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Amplificación de Genes
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Proteínas de Unión al ARN
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Proteínas Oncogénicas
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MicroARNs
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Neuroblastoma
Límite:
Animals
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Female
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Humans
Idioma:
En
Año:
2016
Tipo del documento:
Article