Silencing of PROS1 induces apoptosis and inhibits migration and invasion of glioblastoma multiforme cells

  • Authors:
    • Mohd Firdaus Che Mat
    • Nor Azian Abdul Murad
    • Kamariah Ibrahim
    • Norfilza Mohd Mokhtar
    • Wan Zurinah Wan Ngah
    • Roslan Harun
    • Rahman Jamal
  • View Affiliations

  • Published online on: November 3, 2016     https://doi.org/10.3892/ijo.2016.3755
  • Pages: 2359-2366
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Abstract

Glioblastoma multiforme (GBM) is an aggressive brain tumor and most patients have poor prognosis. Despite many advances in research, there has been no significant improvement in the patient survival rate. New molecular therapies are being studied and RNA interference (RNAi) therapy is one of the promising approaches to improve prognosis and increase survival in patients with GBM. We performed a meta‑analysis of five different microarray datasets and identified 460 significantly upregulated genes in GBM. Loss‑of‑function screening of these upregulated genes using LN18 cells was performed to identify the significant target genes for glioma. Further investigations were performed using siRNA in LN18 cells and various functional assays were carried out on the selected candidate gene to understand further its role in GBM. We identified PROS1 as a candidate gene for GBM from the meta‑analysis and RNAi screening. Knockdown of PROS1 in LN18 cells significantly induced apoptosis compared to siPROS1‑untreated cells (p<0.05). Migration in cells treated with siPROS1 was reduced significantly (p<0.05) and this was confirmed with wound-healing assay. PROS1 knockdown showed substantial reduction in cell invasion up to 82% (p<0.01). In addition, inhibition of PROS1 leads to decrease in cellular proliferation by 18%. Knockdown of PROS1 in LN18 cells caused activation of both of the extrinsic and intrinsic apoptotic pathways. It caused major upregulation of FasL which is important for death receptor signaling activation and also downregulation of GAS6 and other members of TAM family of receptors. PROS1 may play an important role in the development of GBM through cellular proliferation, migration and invasion as well as apoptosis. Targeting PROS1 in GBM could be a novel therapeutic strategy in GBM treatment.
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December-2016
Volume 49 Issue 6

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Che Mat MF, Abdul Murad NA, Ibrahim K, Mohd Mokhtar N, Wan Ngah WZ, Harun R and Jamal R: Silencing of PROS1 induces apoptosis and inhibits migration and invasion of glioblastoma multiforme cells. Int J Oncol 49: 2359-2366, 2016
APA
Che Mat, M.F., Abdul Murad, N.A., Ibrahim, K., Mohd Mokhtar, N., Wan Ngah, W.Z., Harun, R., & Jamal, R. (2016). Silencing of PROS1 induces apoptosis and inhibits migration and invasion of glioblastoma multiforme cells. International Journal of Oncology, 49, 2359-2366. https://doi.org/10.3892/ijo.2016.3755
MLA
Che Mat, M. F., Abdul Murad, N. A., Ibrahim, K., Mohd Mokhtar, N., Wan Ngah, W. Z., Harun, R., Jamal, R."Silencing of PROS1 induces apoptosis and inhibits migration and invasion of glioblastoma multiforme cells". International Journal of Oncology 49.6 (2016): 2359-2366.
Chicago
Che Mat, M. F., Abdul Murad, N. A., Ibrahim, K., Mohd Mokhtar, N., Wan Ngah, W. Z., Harun, R., Jamal, R."Silencing of PROS1 induces apoptosis and inhibits migration and invasion of glioblastoma multiforme cells". International Journal of Oncology 49, no. 6 (2016): 2359-2366. https://doi.org/10.3892/ijo.2016.3755