Silencing of histone deacetylase 6 decreases cellular malignancy and contributes to primary cilium restoration, epithelial-to-mesenchymal transition reversion, and autophagy inhibition in glioblastoma cell lines
Glioblastoma multiforme, the most common type of malignant brain tumor as well as the most aggressive one, lacks an effective therapy. Glioblastoma presents overexpression of mesenchymal markers Snail, Slug, and N-Cadherin and of the autophagic marker p62. Glioblastoma cell lines also present increa...
| Autores: | , , , , , , , , , |
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| Formato: | artículo |
| Fecha de publicación: | 2021 |
| País: | España |
| Recursos: | Universidad de Navarra |
| Repositorio: | Dadun. Depósito Académico Digital de la Universidad de Navarra |
| Idioma: | inglés |
| OAI Identifier: | oai:dadun.unav.edu:10171/68359 |
| Acesso em linha: | https://hdl.handle.net/10171/68359 |
| Access Level: | acceso abierto |
| Palavra-chave: | HDAC6 siRNA Glioblastoma Epithelial-to-mesenchymal transition Primary cilium Autophagy Sonic hedgehog |
| Resumo: | Glioblastoma multiforme, the most common type of malignant brain tumor as well as the most aggressive one, lacks an effective therapy. Glioblastoma presents overexpression of mesenchymal markers Snail, Slug, and N-Cadherin and of the autophagic marker p62. Glioblastoma cell lines also present increased autophagy, overexpression of mesenchymal markers, Shh pathway activation, and lack of primary cilia. In this study, we aimed to evaluate the role of HDAC6 in the pathogenesis of glioblastoma, as HDAC6 is the most overexpressed of all HDACs isoforms in this tumor. We treated glioblastoma cell lines with siHDAC6. HDAC6 silencing inhibited proliferation, migration, and clonogenicity of glioblastoma cell lines. They also reversed the mesenchymal phenotype, decreased autophagy, inhibited Shh pathway, and recovered the expression of primary cilia in glioblastoma cell lines. These results demonstrate that HDAC6 might be a good target for glioblastoma treatment. |
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