P53-induced microRNA-107 inhibits HIF-1 and tumor angiogenesis.
Proc Natl Acad Sci U S A
; 107(14): 6334-9, 2010 Apr 06.
Article
em En
| MEDLINE
| ID: mdl-20308559
ABSTRACT
The pathway involving the tumor suppressor gene TP53 can regulate tumor angiogenesis by unclear mechanisms. Here we show that p53 regulates hypoxic signaling through the transcriptional regulation of microRNA-107 (miR-107). We found that miR-107 is a microRNA expressed by human colon cancer specimens and regulated by p53. miR-107 decreases hypoxia signaling by suppressing expression of hypoxia inducible factor-1beta (HIF-1beta). Knockdown of endogenous miR-107 enhances HIF-1beta expression and hypoxic signaling in human colon cancer cells. Conversely, overexpression of miR-107 inhibits HIF-1beta expression and hypoxic signaling. Furthermore, overexpression of miR-107 in tumor cells suppresses tumor angiogenesis, tumor growth, and tumor VEGF expression in mice. Finally, in human colon cancer specimens, expression of miR-107 is inversely associated with expression of HIF-1beta. Taken together these data suggest that miR-107 can mediate p53 regulation of hypoxic signaling and tumor angiogenesis.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Regulação Neoplásica da Expressão Gênica
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Proteína Supressora de Tumor p53
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MicroRNAs
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Translocador Nuclear Receptor Aril Hidrocarboneto
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Neoplasias
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Neovascularização Patológica
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2010
Tipo de documento:
Article