Upregulation of miR-130b enhances stem cell-like phenotype in glioblastoma by inactivating the Hippo signaling pathway.
Biochem Biophys Res Commun
; 465(2): 194-9, 2015 Sep 18.
Article
em En
| MEDLINE
| ID: mdl-26241672
ABSTRACT
The Hippo signaling pathway plays a crucial role in suppressing tumorigenesis. Physiologically, The Hippo signaling largely restricts its two downstream effectors, homologous oncoproteins Yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ), to a low level of activity by the MST1-SAV1 complex-induced kinase cascade. However, how the negative regulation induced by MST1-SAV1 complex is disrupted to exhibit constitutive YAP/TAZ activation in cancer remains unclear. Herein, we reported that miR-130b directly repressed MST1 and SAV1 expression in human glioblastoma cells. Overexpression of miR-130b induced hyperactivation of the YAP/TAZ and enhanced expression of the Hippo signaling downstream genes CTGF and the pluripotency associated markers, including CD133, SOX2, Nanog, MYC and BMI1, leading to promotion of glioblastoma stem cell phenotype. Conversely, inhibition of miR-130b attenuated these effects. These findings provide a novel mechanism for Hippo signaling inactivation in cancer, indicating not only a potentially pivotal role for miR-130b in the progression of glioblastoma, but also may represent a new therapeutic target.
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MEDLINE
Assunto principal:
Células-Tronco Neoplásicas
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Neoplasias Encefálicas
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Regulação Neoplásica da Expressão Gênica
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Proteínas Serina-Treonina Quinases
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Glioblastoma
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MicroRNAs
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article