MicroRNA-188-5p suppresses tumor cell proliferation and metastasis by directly targeting FGF5 in hepatocellular carcinoma.
J Hepatol
; 63(4): 874-85, 2015 Oct.
Article
en En
| MEDLINE
| ID: mdl-25998163
ABSTRACT
BACKGROUND & AIMS:
Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. However, the detailed molecular mechanisms underlying HCC progression are still not completely clear. Given the crucial role of microRNAs (miRNAs) in cancer metastasis, we aimed to analyze the expression and function of a metastasis-associated miRNA named miR-188-5p in HCC.METHODS:
miRNA array analysis was performed to search for metastasis-associated miRNAs in HCC. miR-188-5p expressions in tumor tissues and adjacent non-tumorous liver tissues of HCC patients and cell lines were evaluated by real-time PCR. The protein expression levels were analyzed by Western blot and immunohistochemistry. Luciferase reporter assays was used to validate the target of miR-188-5p. The effect of miR-188-5p on HCC progression was studied in vitro and in vivo.RESULTS:
miR-188-5p was significantly decreased in HCC and its expression levels were highly correlated with multiple nodules, microvascular invasion, overall and disease-free survival of HCC. Ectopic expression of miR-188-5p suppressed HCC cell proliferation and metastasis in vitro and in vivo. Fibroblast growth factor 5 (FGF5) was identified as a major target of miR-188-5p. Enforced expression of miR-188-5p inhibited the expression of FGF5 significantly and the restoration of FGF5 expression reversed the inhibitory effects of miR-188-5p on HCC cell proliferation and metastasis.CONCLUSIONS:
These findings collectively demonstrate a tumor suppressor role of miR-188-5p in HCC progression via targeting FGF5, suggesting that miR-188-5p could serve as a potential prognostic biomarker and therapeutic target for HCC.Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
ARN Neoplásico
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Regulación Neoplásica de la Expresión Génica
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Carcinoma Hepatocelular
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MicroARNs
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Factor 5 de Crecimiento de Fibroblastos
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Neoplasias Hepáticas
Tipo de estudio:
Observational_studies
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Prognostic_studies
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Risk_factors_studies
Límite:
Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
J Hepatol
Asunto de la revista:
GASTROENTEROLOGIA
Año:
2015
Tipo del documento:
Article
País de afiliación:
China