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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Published inBiology (Basel, Switzerland) Vol. 10; no. 6; p. 467
Main Authors Urdiciain, Alejandro, Erausquin, Elena, Zelaya, María V., Zazpe, Idoya, Lanciego, José L., Meléndez, Bárbara, Rey, Juan A., Idoate, Miguel A., Riobo-Del Galdo, Natalia A., Castresana, Javier S.
Format Journal Article
LanguageEnglish
Published Basel MDPI AG 26.05.2021
MDPI
Subjects
Amino acids
Autophagy
Brain cancer
Brain research
Brain tumors
Cadherins
Cell culture
Cilia
Deacetylation
epithelial-to-mesenchymal transition
Glioblastoma
HDAC6
Hedgehog protein
Histone deacetylase
Isoforms
Malignancy
Mesenchyme
N-Cadherin
Phagocytosis
Phenotypes
Plasmids
primary cilium
Proteins
Reagents
Reversion
siRNA
Therapeutic targets
Tubulin
Tumor cell lines
Tumors
Wound healing
United States > US
Switzerland
Germany
Spain
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Summary: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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ISSN:2079-7737
2079-7737
DOI:10.3390/biology10060467