Journal of Neuro-Oncology

, Volume 112, Issue 2, pp 153–163

Oncogenic effects of miR-10b in glioblastoma stem cells

Authors

  • Fadila Guessous
    • Departments of Microbiology, Immunology and Cancer BiologyUniversity of Virginia
  • Melissa Alvarado-Velez
    • Departments of Microbiology, Immunology and Cancer BiologyUniversity of Virginia
  • Lukasz Marcinkiewicz
    • Departments of Microbiology, Immunology and Cancer BiologyUniversity of Virginia
  • Ying Zhang
    • Departments of Microbiology, Immunology and Cancer BiologyUniversity of Virginia
  • Jungeun Kim
    • Departments of Microbiology, Immunology and Cancer BiologyUniversity of Virginia
  • Simon Heister
    • Departments of Microbiology, Immunology and Cancer BiologyUniversity of Virginia
  • Benjamin Kefas
    • Department of NeurologyUniversity of Virginia
  • Jakub Godlewski
    • Laboratory for Neuro-oncology and NeurosciencesThe Ohio State University
  • David Schiff
    • Department of NeurologyUniversity of Virginia
  • Benjamin Purow
    • Department of NeurologyUniversity of Virginia
    • Departments of Microbiology, Immunology and Cancer BiologyUniversity of Virginia
    • Department of NeurologyUniversity of Virginia
Laboratory Investigation

DOI: 10.1007/s11060-013-1047-0

Cite this article as:
Guessous, F., Alvarado-Velez, M., Marcinkiewicz, L. et al. J Neurooncol (2013) 112: 153. doi:10.1007/s11060-013-1047-0

Abstract

MicroRNAs and cancer stem cells have emerged as critical players in glioblastoma, one of the deadliest human cancers. In this study, we investigated the expression and function of microRNA-10b in glioblastoma cells and stem cells. An analysis of The Cancer Genome Atlas data revealed a correlation between high miR-10b levels and poor prognosis in glioblastoma patients. We measured the levels of miR-10b and found that it is upregulated in human glioblastoma tissues, glioblastoma cell and stem cell lines as compared to normal human tissues or astrocytes. Inhibition of miR-10b with a specific antagomir inhibited the proliferation of glioblastoma established and stem cell lines. Inhibition of miR-10b strongly reduced cell invasion and migration in glioblastoma cell and stem cell lines while overexpression of miR-10b induced cell migration and invasion. We also investigated several predicted targets of miR-10b but could not verify any of them experimentally. Additionally, miR-10b inhibition significantly decreased the in vivo growth of stem cell-derived orthotopic GBM xenografts. Altogether, our findings confirm the oncogenic effects of miR-10b in GBM cells and show for the first time a role of this microRNA in GBM stem cells. Targeting miR-10b might therefore inhibit glioblastoma stem cells, which are thought to be at the origin of glioblastoma and to contribute its recurrence and resistance to therapy.

Keywords

MicroRNA-10bGlioblastomaGlioblastoma stem cellsMigrationInvasion

Copyright information

© Springer Science+Business Media New York 2013