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HGG-27. HNRNPA1 SPLICED VARIANT SENSITIZATION EFFECT DISCLOSED IN GLIOMA CELLS

Glioblastoma is aggressive brain tumor. Glioma heterogeneity builds in hypoxic condition due to its intrinsic high apoptosis rate cause to develop a high selection clonal pressure. HnRNPA1 plays a key role in developing glycolytic tumor, shows its high expression exclusively in hypoxic glioma cells....

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Autor principal: Yadav, Ajay
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8168080/
http://dx.doi.org/10.1093/neuonc/noab090.091
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author Yadav, Ajay
author_facet Yadav, Ajay
author_sort Yadav, Ajay
collection PubMed
description Glioblastoma is aggressive brain tumor. Glioma heterogeneity builds in hypoxic condition due to its intrinsic high apoptosis rate cause to develop a high selection clonal pressure. HnRNPA1 plays a key role in developing glycolytic tumor, shows its high expression exclusively in hypoxic glioma cells. Recently we observed one more spliced variant of hnRNPA1, encoding higher isoform, exclusively abundant in resistant glioma cell lines. Widely around the scientific community HnRNPA1 splice factor family protein was found distinctly regulating resistant glioma phenotype. To support our hypothesis, methodology we perform includes various apoptosis assays to critically understand hnRNPA1 spliced variant dependent pathway in Temozolomide resistant U87 glioma cells. Proteomic based apoptotic array and angiogenic array enable us to visualize selective knock down of hnRNPA1 has dominant role in promoting apoptotic cascade. Additionally, flow cytometry base annexin V-PI staining technique to understand early and late apoptosis was measured in selective hnRNPA1 spliced variant knockdown cells in presence or absence of PI3 kinase inhibitor wortmannin (5 micro molar). Results showed hnRNPA1 higher isoform knock down promotes more apoptosis compare to lower isoform. Interestingly, overexpression of HnRNPA1 higher isoform or lower isoform alone doesn’t promote apoptosis, however is prominently higher apoptosis in Bortezomib treated U87 glioma cells. These both isoforms are presently majorly in gliomas, but somehow for long was not recognized. Conclusion is to explore more related novel finding or therapeutic strategy to target higher isoform of hnRNPA1, using invivo mouse xenograft model.
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spelling pubmed-81680802021-06-02 HGG-27. HNRNPA1 SPLICED VARIANT SENSITIZATION EFFECT DISCLOSED IN GLIOMA CELLS Yadav, Ajay Neuro Oncol High Grade Gliomas Glioblastoma is aggressive brain tumor. Glioma heterogeneity builds in hypoxic condition due to its intrinsic high apoptosis rate cause to develop a high selection clonal pressure. HnRNPA1 plays a key role in developing glycolytic tumor, shows its high expression exclusively in hypoxic glioma cells. Recently we observed one more spliced variant of hnRNPA1, encoding higher isoform, exclusively abundant in resistant glioma cell lines. Widely around the scientific community HnRNPA1 splice factor family protein was found distinctly regulating resistant glioma phenotype. To support our hypothesis, methodology we perform includes various apoptosis assays to critically understand hnRNPA1 spliced variant dependent pathway in Temozolomide resistant U87 glioma cells. Proteomic based apoptotic array and angiogenic array enable us to visualize selective knock down of hnRNPA1 has dominant role in promoting apoptotic cascade. Additionally, flow cytometry base annexin V-PI staining technique to understand early and late apoptosis was measured in selective hnRNPA1 spliced variant knockdown cells in presence or absence of PI3 kinase inhibitor wortmannin (5 micro molar). Results showed hnRNPA1 higher isoform knock down promotes more apoptosis compare to lower isoform. Interestingly, overexpression of HnRNPA1 higher isoform or lower isoform alone doesn’t promote apoptosis, however is prominently higher apoptosis in Bortezomib treated U87 glioma cells. These both isoforms are presently majorly in gliomas, but somehow for long was not recognized. Conclusion is to explore more related novel finding or therapeutic strategy to target higher isoform of hnRNPA1, using invivo mouse xenograft model. Oxford University Press 2021-06-01 /pmc/articles/PMC8168080/ http://dx.doi.org/10.1093/neuonc/noab090.091 Text en © The Author(s) 2021. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com. https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) ), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle High Grade Gliomas
Yadav, Ajay
HGG-27. HNRNPA1 SPLICED VARIANT SENSITIZATION EFFECT DISCLOSED IN GLIOMA CELLS
title HGG-27. HNRNPA1 SPLICED VARIANT SENSITIZATION EFFECT DISCLOSED IN GLIOMA CELLS
title_full HGG-27. HNRNPA1 SPLICED VARIANT SENSITIZATION EFFECT DISCLOSED IN GLIOMA CELLS
title_fullStr HGG-27. HNRNPA1 SPLICED VARIANT SENSITIZATION EFFECT DISCLOSED IN GLIOMA CELLS
title_full_unstemmed HGG-27. HNRNPA1 SPLICED VARIANT SENSITIZATION EFFECT DISCLOSED IN GLIOMA CELLS
title_short HGG-27. HNRNPA1 SPLICED VARIANT SENSITIZATION EFFECT DISCLOSED IN GLIOMA CELLS
title_sort hgg-27. hnrnpa1 spliced variant sensitization effect disclosed in glioma cells
topic High Grade Gliomas
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8168080/
http://dx.doi.org/10.1093/neuonc/noab090.091
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