title: Oncogenic effects of miR-10b in glioblastoma stem cells.
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.
authors: Departments of Microbiology, Immunology and Cancer Biology, University of Virginia, Charlottesville, VA 22908, USA.
authors: Fadila
authors: F
authors: Guessous
authors: Melissa
authors: M
authors: Alvarado-Velez
authors: Lukasz
authors: L
authors: Marcinkiewicz
authors: Ying
authors: Y
authors: Zhang
authors: Jungeun
authors: J
authors: Kim
authors: Simon
authors: S
authors: Heister
authors: Benjamin
authors: B
authors: Kefas
authors: Jakub
authors: J
authors: Godlewski
authors: David
authors: D
authors: Schiff
authors: Benjamin
authors: B
authors: Purow
authors: Roger
authors: R
authors: Abounader
mesh_terms: D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism*; D001932:Brain Neoplasms / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D002448:Cell Adhesion; D002465:Cell Movement; D049109:Cell Proliferation; D015972:Gene Expression Regulation, Neoplastic; D005909:Glioblastoma / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D014411:Neoplastic Stem Cells / Q000378:metabolism*; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D023041:Xenograft Model Antitumor Assays
chemical_list: C547183:MIRN10 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger