microRNA-608 inhibits human hepatocellular carcinoma cell proliferation via targeting the BET family protein BRD4.
Biochem Biophys Res Commun
; 501(4): 1060-1067, 2018 07 02.
Article
en En
| MEDLINE
| ID: mdl-29777702
ABSTRACT
Over-expression of the bromodomain and extraterminal (BET) family protein BRD4 is associated with hepatocellular carcinoma (HCC) progression. In the present study, we indentified a novel putative anti-BRD4 microRNA microRNA-608 ("miR-608"). In HepG2 cells and primary human HCC cells, over-expression of miR-608, using a lentiviral construct, induced BRD4 downregulation and proliferation inhibition. Conversely, transfection of the miR-608 inhibitor increased BRD4 expression to promote HepG2 cell proliferation. Our results suggest that BRD4 is the primary target gene of miR-608 in HepG2 cells. shRNA-mediated knockdown or CRSIPR/Cas9-mediated knockout of BRD4 mimicked and overtook miR-608's actions in HepG2 cells. Furthermore, introduction of a 3'-untranslated region (3'-UTR) mutant BRD4 (UTR-A1718G) blocked miR-608-induced c-Myc downregulation and proliferation inhibition in HepG2 cells. In vivo, HepG2 xenograft tumor growth was significantly inhibited after expressing miR-608 or BRD4 CRSIPR/Cas9-KO construct. Importantly, BRD4 mRNA was upregulated in human HCC tissues, which was correlated with downregulation of miR-608. Together, we conclude that miR-608 inhibits HCC cell proliferation possibly via targeting BET family protein BRD4.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Factores de Transcripción
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Proteínas Nucleares
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Carcinoma Hepatocelular
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MicroARNs
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Neoplasias Hepáticas
Tipo de estudio:
Prognostic_studies
Límite:
Animals
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Humans
Idioma:
En
Revista:
Biochem Biophys Res Commun
Año:
2018
Tipo del documento:
Article
País de afiliación:
China