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14-3-3ζ negatively regulates mitochondrial biogenesis in GBM residual cells
Glioblastoma (GBM) is the most lethal primary brain tumour with a median survival of only 15 months. We have previously demonstrated the generation of an in vitro therapy resistance model that captures the residual resistant (RR) disease cells of GBM post-radiation. We also reported the proteomic la...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8605068/ https://www.ncbi.nlm.nih.gov/pubmed/34825085 http://dx.doi.org/10.1016/j.heliyon.2021.e08371 |
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author | Rajendra, Jacinth Ghorai, Atanu Dutt, Shilpee |
author_facet | Rajendra, Jacinth Ghorai, Atanu Dutt, Shilpee |
author_sort | Rajendra, Jacinth |
collection | PubMed |
description | Glioblastoma (GBM) is the most lethal primary brain tumour with a median survival of only 15 months. We have previously demonstrated the generation of an in vitro therapy resistance model that captures the residual resistant (RR) disease cells of GBM post-radiation. We also reported the proteomic landscape of parent, residual, and relapse cells using iTRAQ based quantitative proteomics of glioma cells. The proteomics data revealed significant up-regulation (fold change >1.5) of 14-3-3ζ, specifically in GBM RR cells. This was further confirmed by western blots in residual cells generated from GBM cell lines and patient sample-derived short-term primary culture. ShRNA-mediated knockdown of 14-3-3ζ radio-sensitized GBM cells and further stimulated therapy-induced senescence (TIS) and multinucleated giant cells (MNGCs) phenotype in RR cells. Intriguingly, 14-3-3ζ knockdown residual cells also showed a significantly higher number of mitochondria and increased mtDNA content. Indeed, in vitro GST pull-down mass spectrometry analysis of GST tagged 14-3-3ζ from RR cells identified novel interacting partners of 14-3-3ζ involved in cellular metabolism. Taken together, here we identified novel interacting partners of 14-3-3ζ and proposed an unconventional function of 14-3-3ζ as a negative regulator of TIS and mitochondrial biogenesis in residual resistant cells and loss of which also radio-sensitize GBM cells. |
format | Online Article Text |
id | pubmed-8605068 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-86050682021-11-24 14-3-3ζ negatively regulates mitochondrial biogenesis in GBM residual cells Rajendra, Jacinth Ghorai, Atanu Dutt, Shilpee Heliyon Research Article Glioblastoma (GBM) is the most lethal primary brain tumour with a median survival of only 15 months. We have previously demonstrated the generation of an in vitro therapy resistance model that captures the residual resistant (RR) disease cells of GBM post-radiation. We also reported the proteomic landscape of parent, residual, and relapse cells using iTRAQ based quantitative proteomics of glioma cells. The proteomics data revealed significant up-regulation (fold change >1.5) of 14-3-3ζ, specifically in GBM RR cells. This was further confirmed by western blots in residual cells generated from GBM cell lines and patient sample-derived short-term primary culture. ShRNA-mediated knockdown of 14-3-3ζ radio-sensitized GBM cells and further stimulated therapy-induced senescence (TIS) and multinucleated giant cells (MNGCs) phenotype in RR cells. Intriguingly, 14-3-3ζ knockdown residual cells also showed a significantly higher number of mitochondria and increased mtDNA content. Indeed, in vitro GST pull-down mass spectrometry analysis of GST tagged 14-3-3ζ from RR cells identified novel interacting partners of 14-3-3ζ involved in cellular metabolism. Taken together, here we identified novel interacting partners of 14-3-3ζ and proposed an unconventional function of 14-3-3ζ as a negative regulator of TIS and mitochondrial biogenesis in residual resistant cells and loss of which also radio-sensitize GBM cells. Elsevier 2021-11-12 /pmc/articles/PMC8605068/ /pubmed/34825085 http://dx.doi.org/10.1016/j.heliyon.2021.e08371 Text en © 2021 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Research Article Rajendra, Jacinth Ghorai, Atanu Dutt, Shilpee 14-3-3ζ negatively regulates mitochondrial biogenesis in GBM residual cells |
title | 14-3-3ζ negatively regulates mitochondrial biogenesis in GBM residual cells |
title_full | 14-3-3ζ negatively regulates mitochondrial biogenesis in GBM residual cells |
title_fullStr | 14-3-3ζ negatively regulates mitochondrial biogenesis in GBM residual cells |
title_full_unstemmed | 14-3-3ζ negatively regulates mitochondrial biogenesis in GBM residual cells |
title_short | 14-3-3ζ negatively regulates mitochondrial biogenesis in GBM residual cells |
title_sort | 14-3-3ζ negatively regulates mitochondrial biogenesis in gbm residual cells |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8605068/ https://www.ncbi.nlm.nih.gov/pubmed/34825085 http://dx.doi.org/10.1016/j.heliyon.2021.e08371 |
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