Knockdown of Tousled‑like kinase 1 inhibits survival of glioblastoma multiforme cells
- Kamariah Ibrahim
- Nor Azian Abdul Murad
- Roslan Harun
- Rahman Jamal
Affiliations: UKM Medical Molecular Biology Institute, Universiti Kebangsaan Malaysia, Kuala Lumpur 56000, Malaysia, KPJ Ampang Puteri Specialist Hospital, Ampang, Selangor 68000, Malaysia
- Published online on: May 28, 2020 https://doi.org/10.3892/ijmm.2020.4619
Copyright : © Ibrahim
et al. This is an open access article distributed under the
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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.