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
Department of Biochemistry and Genetics, University of Navarra School of Sciences, 31008 Pamplona, Spain.
Department of Pathology, Hospital Complex of Navarra, 31008 Pamplona, Spain.
Biology (Basel). 2021 May 26;10(6):467. doi: 10.3390/biology10060467.
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.
多形性胶质母细胞瘤是最常见且最具侵袭性的恶性脑肿瘤类型，目前缺乏有效的治疗方法。胶质母细胞瘤表现为间充质标志物Snail、Slug和N-钙黏蛋白以及自噬标志物p62的过表达。胶质母细胞瘤细胞系还表现出自噬增加、间充质标志物过表达、Shh通路激活以及缺乏初级纤毛。在本研究中，我们旨在评估HDAC6在胶质母细胞瘤发病机制中的作用，因为HDAC6是该肿瘤中所有HDAC异构体中过表达最为明显的。我们用siHDAC6处理胶质母细胞瘤细胞系。HDAC6沉默抑制了胶质母细胞瘤细胞系的增殖、迁移和克隆形成能力。它们还逆转了间充质表型，减少了自噬，抑制了Shh通路，并恢复了胶质母细胞瘤细胞系中初级纤毛的表达。这些结果表明，HDAC6可能是胶质母细胞瘤治疗的一个良好靶点。
