E2F1-regulated microRNAs impair TGFbeta-dependent cell-cycle arrest and apoptosis in gastric cancer.
Cancer Cell
; 13(3): 272-86, 2008 Mar.
Article
em En
| MEDLINE
| ID: mdl-18328430
ABSTRACT
Deregulation of E2F1 activity and resistance to TGFbeta are hallmarks of gastric cancer. MicroRNAs (miRNAs) are small noncoding RNAs frequently misregulated in human malignancies. Here we provide evidence that the miR-106b-25 cluster, upregulated in a subset of human gastric tumors, is activated by E2F1 in parallel with its host gene, Mcm7. In turn, miR-106b and miR-93 regulate E2F1 expression, establishing a miRNA-directed negative feedback loop. Furthermore, upregulation of these miRNAs impairs the TGFbeta tumor suppressor pathway, interfering with the expression of CDKN1A (p21(Waf1/Cip1)) and BCL2L11 (Bim). Together, these results suggest that the miR-106b-25 cluster is involved in E2F1 posttranscriptional regulation and may play a key role in the development of TGFbeta resistance in gastric cancer.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Gástricas
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Adenocarcinoma
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Regulação Neoplásica da Expressão Gênica
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Ciclo Celular
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Processamento Pós-Transcricional do RNA
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Fator de Crescimento Transformador beta
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Apoptose
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MicroRNAs
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Fator de Transcrição E2F1
Limite:
Humans
Idioma:
En
Revista:
Cancer Cell
Assunto da revista:
NEOPLASIAS
Ano de publicação:
2008
Tipo de documento:
Article
País de afiliação:
Estados Unidos