Journal of Neuro-Oncology

, Volume 112, Issue 2, pp 153–163 | Cite as

Oncogenic effects of miR-10b in glioblastoma stem cells

  • Fadila Guessous
  • Melissa Alvarado-Velez
  • Lukasz Marcinkiewicz
  • Ying Zhang
  • Jungeun Kim
  • Simon Heister
  • Benjamin Kefas
  • Jakub Godlewski
  • David Schiff
  • Benjamin Purow
  • Roger Abounader
Laboratory Investigation

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-10b Glioblastoma Glioblastoma stem cells Migration Invasion 

Notes

Acknowledgments

Supported by NIH RO1 NS045209 (R. Abounader) and NIH R01 CA134843 (R. Abounader).

Conflict of interest

None of the authors has any conflict of interest associated with the present work.

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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Fadila Guessous
    • 1
  • Melissa Alvarado-Velez
    • 1
  • Lukasz Marcinkiewicz
    • 1
  • Ying Zhang
    • 1
  • Jungeun Kim
    • 1
  • Simon Heister
    • 1
  • Benjamin Kefas
    • 2
  • Jakub Godlewski
    • 3
  • David Schiff
    • 2
  • Benjamin Purow
    • 2
  • Roger Abounader
    • 1
    • 2
  1. 1.Departments of Microbiology, Immunology and Cancer BiologyUniversity of VirginiaCharlottesvilleUSA
  2. 2.Department of NeurologyUniversity of VirginiaCharlottesvilleUSA
  3. 3.Laboratory for Neuro-oncology and NeurosciencesThe Ohio State UniversityColumbusUSA

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