miR-98 suppresses melanoma metastasis through a negative feedback loop with its target gene IL-6
Experimental & Molecular Medicine
; : e116-2014.
Article
em En
| WPRIM
| ID: wpr-222036
Biblioteca responsável:
WPRO
ABSTRACT
Dysregulated microRNA (miRNA) expression has a critical role in tumor development and metastasis. However, the mechanism by which miRNAs control melanoma metastasis is unknown. Here, we report reduced miR-98 expression in melanoma tissues with increasing tumor stage as well as metastasis; its expression is also negatively associated with melanoma patient survival. Furthermore, we demonstrate that miR-98 inhibits melanoma cell migration in vitro as well as metastatic tumor size in vivo. We also found that IL-6 is a target gene of miR-98, and IL-6 represses miR-98 levels via the Stat3-NF-kappaB-lin28B pathway. In an in vivo melanoma model, we demonstrate that miR-98 reduces melanoma metastasis and increases survival in part by reducing IL-6 levels; it also decreases Stat3 and p65 phosphorylation as well as lin28B mRNA levels. These results suggest that miR-98 inhibits melanoma metastasis in part through a novel miR-98-IL-6-negative feedback loop.
Texto completo:
1
Índice:
WPRIM
Assunto principal:
Transdução de Sinais
/
Regulação para Baixo
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Regulação Neoplásica da Expressão Gênica
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Análise de Sobrevida
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Interleucina-6
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MicroRNAs
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Linhagem Celular Tumoral
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Melanoma
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Camundongos Endogâmicos C57BL
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Metástase Neoplásica
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Humans
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Male
Idioma:
En
Revista:
Experimental & Molecular Medicine
Ano de publicação:
2014
Tipo de documento:
Article