Oncogenic effects of miR-10b in glioblastoma stem cells
- PDF / 2,141,951 Bytes
- 11 Pages / 595.276 x 790.866 pts Page_size
- 101 Downloads / 185 Views
LABORATORY INVESTIGATION
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
Received: 13 September 2012 / Accepted: 1 January 2013 / Published online: 10 January 2013 Ó Springer Science+Business Media New York 2013
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 miR10b 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 F. Guessous M. Alvarado-Velez L. Marcinkiewicz Y. Zhang J. Kim S. Heister R. Abounader (&) Departments of Microbiology, Immunology and Cancer Biology, University of Virginia, PO Box 800168, Charlottesville, VA 22908, USA e-mail: [email protected] B. Kefas D. Schiff B. Purow R. Abounader Department of Neurology, University of Virginia, PO Box 800168, Charlottesville, VA 22908, USA J. Godlewski Laboratory for Neuro-oncology and Neurosciences, The Ohio State University, Columbus, OH, USA
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
Introduction Gliomas are extremely aggressive brain tumors that account for the majority of deaths due to primary brain neoplasms. Grade IV glioma, glioblastoma (GBM) is the most frequently diagnosed glioma and one of the least successfully treated human tumors [1]. Despite recent therapeutic advances, GBM treatment combining surgical resection, chemotherapy and radiotherapy remains ineffective and is associated with an average life expectancy of 12–15 months [2]. The origin of GBM is largely unknown but there is an increasing speculation that they arise from a subset of cells, called GBM stem cells, that putatively consist
Data Loading...
