Alshawli, AS, Wurdak, H, Wood, IC orcid.org/0000-0003-1886-2533 et al. (1 more author) (2020) Histone deacetylase inhibitors induce medulloblastoma cell death independent of HDACs recruited in REST repression complexes. Molecular Genetics & Genomic Medicine, 8 (10). e1429. ISSN 2324-9269
Abstract
Background
Repressor element 1‐silencing transcription factor (REST) acts as a transcriptional repressor by recruiting several chromatin modifiers, including histone deacetylase (HDAC). Elevated REST expression in medulloblastoma has been associated with tumor progression nevertheless, the tumor shows high sensitivity to HDAC inhibitors (HDACi). However, the functional implications of REST and its requirement for HDACi‐induced anti‐cancer effects are not well understood.
Methods
In this study, the expression of REST was evaluated across the medulloblastoma subgroups and subtypes using published gene expression data. Further, the expression of REST was modulated using the CRISPR/Cas9 knockout and shRNA knockdown in the Daoy medulloblastoma cell line.
Results
The results of this study showed that the expression of REST is elevated in most medulloblastoma subgroups compared to the non‐cancerous cerebellum. Blocking of REST expression resulted in increasing the expression of REST‐regulated genes, a moderate decrease in the fraction of the cells in the S‐phase, and reducing the cells' migration ability. However, REST deficiency did not lead to a marked decrease in the Daoy cell viability and sensitivity to HDACi.
Conclusion
The findings of this study indicate that REST is not essential for sustaining the proliferation/viability of the Daoy cells. It also revealed that the anti‐proliferative effect of HDACi is independent of REST expression.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2020 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
Keywords: | CRISPR/Cas9 ; HDAC ; HDACi ; medulloblastoma ; REST ; shRNA |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Biological Sciences (Leeds) > School of Biomedical Sciences (Leeds) The University of Leeds > Faculty of Biological Sciences (Leeds) > School of Molecular and Cellular Biology (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 10 Aug 2020 14:51 |
Last Modified: | 25 Jun 2023 22:22 |
Status: | Published |
Publisher: | Wiley Open Access |
Identification Number: | 10.1002/mgg3.1429 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:164028 |