TGF-ß1 suppression of microRNA-450b-5p expression: a novel mechanism for blocking myogenic differentiation of rhabdomyosarcoma.
Oncogene
; 33(16): 2075-86, 2014 Apr 17.
Article
em En
| MEDLINE
| ID: mdl-23665678
ABSTRACT
Transforming growth factor beta 1 (TGF-ß1) is the most potent inhibitor of myogenic differentiation (MyoD) of rhabdomyosarcoma (RMS); however, the underlying mechanisms of this inhibition remain unclear. In this study, we identified novel TGF-ß1-related microRNAs (miRNAs); among these, miR-450b-5p is significantly regulated by TGF-ß1. We provide evidence that TGF-ß1 exerts it function by suppressing miR-450b-5p. Both in cultured cells and tumor implants, miR-450b-5p significantly arrested the growth of RMS and promoted its MyoD. Utilizing a bioinformatics approach, we identified miR-450b-5p target mRNAs. Among these candidates, only the expression of ecto-NOX disulfide-thiol exchanger 2 (ENOX2) and paired box 9 (PAX9) was augmented by miR-450b-5p knockdown examined by western blot; the engineered inhibition antagonized TGF-ß1-mediated differentiation inhibition. Furthermore, we found that the Smad3 and Smad4 pathways, but not Smad2, are the principal mediator of TGF-ß1 suppression of miR-450b-5p. Taken together, these results suggest that disrupting the TGF-ß1 suppression of miR-450b-5p, or knockdown of ENOX2 and PAX9, are effective approaches in inducing RMS MyoD.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Rabdomiossarcoma
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Regulação Neoplásica da Expressão Gênica
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Proteína MyoD
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MicroRNAs
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Fator de Crescimento Transformador beta1
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Humans
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Male
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article