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

Biology

JavierS. Castresana¹  Alejandro Urdiciain¹  Elena Erausquin¹  Idoya Zazpe²  MaríaV. Zelaya³  MiguelA. Idoate⁴  JuanA. Rey⁵  Bárbara Meléndez⁶  JoséL. Lanciego⁷  NataliaA. Riobo-Del Galdo⁸ 

[1] Department of Biochemistry and Genetics, University of Navarra School of Sciences, 31008 Pamplona, Spain;Department of Neurosurgery, Hospital Complex of Navarra, 31008 Pamplona, Spain;Department of Pathology, Hospital Complex of Navarra, 31008 Pamplona, Spain;Department of Pathology, University of Navarra Clinic, 31008 Pamplona, Spain;IdiPaz Research Unit, La Paz University Hospital, 28046 Madrid, Spain;Molecular Pathology Research Unit, Virgen de la Salud Hospital, 45005 Toledo, Spain;Neurosciences Division, Center for Applied Medical Research (CIMA), University of Navarra, 31008 Pamplona, Spain;School of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, UK;

关键词: HDAC6;    siRNA;    glioblastoma;    epithelial-to-mesenchymal transition;    primary cilium;    autophagy;   

DOI  :  10.3390/biology10060467

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown