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

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...

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Main Authors: Alejandro Urdiciain, Elena Erausquin, María V. Zelaya, Idoya Zazpe, José L. Lanciego, Bárbara Meléndez, Juan A. Rey, Miguel A. Idoate, Natalia A. Riobo-Del Galdo, Javier S. Castresana
Format: Article
Language:English
Published: MDPI AG 2021-05-01
Series:Biology
Subjects:
HDAC6
siRNA
glioblastoma
epithelial-to-mesenchymal transition
primary cilium
autophagy
Online Access:https://www.mdpi.com/2079-7737/10/6/467
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spelling doaj-bdc0fba0691247a994f9dd392c66f8c42021-06-01T01:08:26ZengMDPI AGBiology2079-77372021-05-011046746710.3390/biology10060467Silencing of Histone Deacetylase 6 Decreases Cellular Malignancy and Contributes to Primary Cilium Restoration, Epithelial-to-Mesenchymal Transition Reversion, and Autophagy Inhibition in Glioblastoma Cell LinesAlejandro Urdiciain0Elena Erausquin1María V. Zelaya2Idoya Zazpe3José L. Lanciego4Bárbara Meléndez5Juan A. Rey6Miguel A. Idoate7Natalia A. Riobo-Del Galdo8Javier S. Castresana9Department of Biochemistry and Genetics, University of Navarra School of Sciences, 31008 Pamplona, SpainDepartment of Biochemistry and Genetics, University of Navarra School of Sciences, 31008 Pamplona, SpainDepartment of Pathology, Hospital Complex of Navarra, 31008 Pamplona, SpainDepartment of Neurosurgery, Hospital Complex of Navarra, 31008 Pamplona, SpainNeurosciences Division, Center for Applied Medical Research (CIMA), University of Navarra, 31008 Pamplona, SpainMolecular Pathology Research Unit, Virgen de la Salud Hospital, 45005 Toledo, SpainIdiPaz Research Unit, La Paz University Hospital, 28046 Madrid, SpainDepartment of Pathology, University of Navarra Clinic, 31008 Pamplona, SpainSchool of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, UKDepartment of Biochemistry and Genetics, University of Navarra School of Sciences, 31008 Pamplona, SpainGlioblastoma 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.https://www.mdpi.com/2079-7737/10/6/467HDAC6siRNAglioblastomaepithelial-to-mesenchymal transitionprimary ciliumautophagy
collection DOAJ
language English
format Article
sources DOAJ
author Alejandro Urdiciain
Elena Erausquin
María V. Zelaya
Idoya Zazpe
José L. Lanciego
Bárbara Meléndez
Juan A. Rey
Miguel A. Idoate
Natalia A. Riobo-Del Galdo
Javier S. Castresana
spellingShingle Alejandro Urdiciain
Elena Erausquin
María V. Zelaya
Idoya Zazpe
José L. Lanciego
Bárbara Meléndez
Juan A. Rey
Miguel A. Idoate
Natalia A. Riobo-Del Galdo
Javier S. Castresana
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
HDAC6
siRNA
glioblastoma
epithelial-to-mesenchymal transition
primary cilium
autophagy
author_facet Alejandro Urdiciain
Elena Erausquin
María V. Zelaya
Idoya Zazpe
José L. Lanciego
Bárbara Meléndez
Juan A. Rey
Miguel A. Idoate
Natalia A. Riobo-Del Galdo
Javier S. Castresana
author_sort Alejandro Urdiciain
title 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
title_short 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_sort 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
publisher MDPI AG
series Biology
issn 2079-7737
publishDate 2021-05-01
description 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.
topic HDAC6
siRNA
glioblastoma
epithelial-to-mesenchymal transition
primary cilium
autophagy
url https://www.mdpi.com/2079-7737/10/6/467
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