Open Access

Knockdown of Tousled‑like kinase 1 inhibits survival of glioblastoma multiforme cells

  • Authors:
    • Kamariah Ibrahim
    • Nor Azian Abdul Murad
    • Roslan Harun
    • Rahman Jamal
  • View Affiliations

  • Published online on: May 28, 2020     https://doi.org/10.3892/ijmm.2020.4619
  • Pages: 685-699
  • Copyright : © Ibrahim et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY 4.0].

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

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.
View Figures
View References

Related Articles

Journal Cover

August-2020
Volume 46 Issue 2

Print ISSN: 1107-3756
Online ISSN:1791-244X

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos
Ibrahim K, Abdul Murad NA, Harun R and Jamal R: Knockdown of Tousled‑like kinase 1 inhibits survival of glioblastoma multiforme cells. Int J Mol Med 46: 685-699, 2020
APA
Ibrahim, K., Abdul Murad, N.A., Harun, R., & Jamal, R. (2020). Knockdown of Tousled‑like kinase 1 inhibits survival of glioblastoma multiforme cells. International Journal of Molecular Medicine, 46, 685-699. https://doi.org/10.3892/ijmm.2020.4619
MLA
Ibrahim, K., Abdul Murad, N. A., Harun, R., Jamal, R."Knockdown of Tousled‑like kinase 1 inhibits survival of glioblastoma multiforme cells". International Journal of Molecular Medicine 46.2 (2020): 685-699.
Chicago
Ibrahim, K., Abdul Murad, N. A., Harun, R., Jamal, R."Knockdown of Tousled‑like kinase 1 inhibits survival of glioblastoma multiforme cells". International Journal of Molecular Medicine 46, no. 2 (2020): 685-699. https://doi.org/10.3892/ijmm.2020.4619