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Knockdown of Tousled-like kinase 1 inhibits survival of glioblastoma multiforme cells
Glioblastoma multiforme (GBM) is an aggressive type of brain tumour that commonly exhibits resistance to treatment. The tumour is highly heterogenous and complex kinomic alterations have been reported leading to dysregulation of signalling pathways. The present study aimed to investigate the novel k...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
D.A. Spandidos
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7307829/ https://www.ncbi.nlm.nih.gov/pubmed/32468002 http://dx.doi.org/10.3892/ijmm.2020.4619 |
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author | Ibrahim, Kamariah Murad, Nor Azian Abdul Harun, Roslan Jamal, Rahman |
author_facet | Ibrahim, Kamariah Murad, Nor Azian Abdul Harun, Roslan Jamal, Rahman |
author_sort | Ibrahim, Kamariah |
collection | PubMed |
description | Glioblastoma multiforme (GBM) is an aggressive type of brain tumour that commonly exhibits resistance to treatment. The tumour is highly heterogenous and complex kinomic alterations have been reported leading to dysregulation of signalling pathways. The present study aimed to investigate the novel kinome pathways and to identify potential therapeutic targets in GBM. Meta-analysis using Oncomine identified 113 upregulated kinases in GBM. RNAi screening was performed on identified kinases using ON-TARGETplus siRNA library on LN18 and U87MG. Tousled-like kinase 1 (TLK1), which is a serine/threonine kinase was identified as a potential hit. In vitro functional validation was performed as the role of TLK1 in GBM is unknown. TLK1 knockdown in GBM cells significantly decreased cell viability, clonogenicity, proliferation and induced apoptosis. TLK1 knockdown also chemosensitised the GBM cells to the sublethal dose of temozolomide. The downstream pathways of TLK1 were examined using microarray analysis, which identified the involvement of DNA replication, cell cycle and focal adhesion signalling pathways. In vivo validation of the subcutaneous xenografts of stably transfected sh-TLK1 U87MG cells demonstrated significantly decreased tumour growth in female BALB/c nude mice. Together, these results suggested that TLK1 may serve a role in GBM survival and may serve as a potential target for glioma. |
format | Online Article Text |
id | pubmed-7307829 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | D.A. Spandidos |
record_format | MEDLINE/PubMed |
spelling | pubmed-73078292020-06-23 Knockdown of Tousled-like kinase 1 inhibits survival of glioblastoma multiforme cells Ibrahim, Kamariah Murad, Nor Azian Abdul Harun, Roslan Jamal, Rahman Int J Mol Med Articles Glioblastoma multiforme (GBM) is an aggressive type of brain tumour that commonly exhibits resistance to treatment. The tumour is highly heterogenous and complex kinomic alterations have been reported leading to dysregulation of signalling pathways. The present study aimed to investigate the novel kinome pathways and to identify potential therapeutic targets in GBM. Meta-analysis using Oncomine identified 113 upregulated kinases in GBM. RNAi screening was performed on identified kinases using ON-TARGETplus siRNA library on LN18 and U87MG. Tousled-like kinase 1 (TLK1), which is a serine/threonine kinase was identified as a potential hit. In vitro functional validation was performed as the role of TLK1 in GBM is unknown. TLK1 knockdown in GBM cells significantly decreased cell viability, clonogenicity, proliferation and induced apoptosis. TLK1 knockdown also chemosensitised the GBM cells to the sublethal dose of temozolomide. The downstream pathways of TLK1 were examined using microarray analysis, which identified the involvement of DNA replication, cell cycle and focal adhesion signalling pathways. In vivo validation of the subcutaneous xenografts of stably transfected sh-TLK1 U87MG cells demonstrated significantly decreased tumour growth in female BALB/c nude mice. Together, these results suggested that TLK1 may serve a role in GBM survival and may serve as a potential target for glioma. D.A. Spandidos 2020-08 2020-05-28 /pmc/articles/PMC7307829/ /pubmed/32468002 http://dx.doi.org/10.3892/ijmm.2020.4619 Text en Copyright: © Ibrahim et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. |
spellingShingle | Articles Ibrahim, Kamariah Murad, Nor Azian Abdul Harun, Roslan Jamal, Rahman Knockdown of Tousled-like kinase 1 inhibits survival of glioblastoma multiforme cells |
title | Knockdown of Tousled-like kinase 1 inhibits survival of glioblastoma multiforme cells |
title_full | Knockdown of Tousled-like kinase 1 inhibits survival of glioblastoma multiforme cells |
title_fullStr | Knockdown of Tousled-like kinase 1 inhibits survival of glioblastoma multiforme cells |
title_full_unstemmed | Knockdown of Tousled-like kinase 1 inhibits survival of glioblastoma multiforme cells |
title_short | Knockdown of Tousled-like kinase 1 inhibits survival of glioblastoma multiforme cells |
title_sort | knockdown of tousled-like kinase 1 inhibits survival of glioblastoma multiforme cells |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7307829/ https://www.ncbi.nlm.nih.gov/pubmed/32468002 http://dx.doi.org/10.3892/ijmm.2020.4619 |
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