title: DICER governs characteristics of glioma stem cells and the resulting tumors in xenograft mouse models of glioblastoma.
abstract: The RNAse III endonuclease DICER is a key regulator of microRNA (miRNA) biogenesis and is frequently decreased in a variety of malignancies. We characterized the role of DICER in glioblastoma (GB), specifically demonstrating its effects on the ability of glioma stem-like cells (GSCs) to form tumors in a mouse model of GB. DICER silencing in GSCs reduced their stem cell characteristics, while tumors arising from these cells were more aggressive, larger in volume, and displayed a higher proliferation index and lineage differentiation. The resulting tumors, however, were more sensitive to radiation treatment. Our results demonstrate that DICER silencing enhances the tumorigenic potential of GSCs, providing a platform for analysis of specific relevant miRNAs and development of potentially novel therapies against GB.
authors.affiliation: Princess Margaret Cancer Centre and MacFeeters-Hamilton Centre for Neuro-Oncology Research, Toronto, ON, Canada.
authors.forename: Sheila
authors.initials: S
authors.lastname: Mansouri
authors.affiliation: Princess Margaret Cancer Centre and MacFeeters-Hamilton Centre for Neuro-Oncology Research, Toronto, ON, Canada.
authors.forename: Sanjay
authors.initials: S
authors.lastname: Singh
authors.affiliation: Princess Margaret Cancer Centre and MacFeeters-Hamilton Centre for Neuro-Oncology Research, Toronto, ON, Canada.
authors.forename: Amir
authors.initials: A
authors.lastname: Alamsahebpour
authors.affiliation: Princess Margaret Cancer Centre and MacFeeters-Hamilton Centre for Neuro-Oncology Research, Toronto, ON, Canada.
authors.forename: Kelly
authors.initials: K
authors.lastname: Burrell
authors.affiliation: Princess Margaret Cancer Centre and MacFeeters-Hamilton Centre for Neuro-Oncology Research, Toronto, ON, Canada.
authors.forename: Mira
authors.initials: M
authors.lastname: Li
authors.affiliation: School of Medicine, Koç University, Rumelifeneri Yolu, Sariyer, Istanbul, Turkey.
authors.forename: Merve
authors.initials: M
authors.lastname: Karabork
authors.affiliation: School of Medicine, Koç University, Rumelifeneri Yolu, Sariyer, Istanbul, Turkey.
authors.forename: Can
authors.initials: C
authors.lastname: Ekinci
authors.affiliation: Ontario Cancer Institute and Campbell Family Institute for Cancer Research, Princess Margaret Cancer Centre, Toronto, ON, Canada.|Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Koch
authors.affiliation: School of Medicine, Koç University, Rumelifeneri Yolu, Sariyer, Istanbul, Turkey.|Loma Linda University, School of Medicine, Loma Linda, CA, USA.
authors.forename: Ihsan
authors.initials: I
authors.lastname: Solaroglu
authors.affiliation: Department of Integrative Biology and Pharmacology, McGovern Medical School, University of Texas, Houston, TX, USA.
authors.forename: Jeffery T
authors.initials: JT
authors.lastname: Chang
authors.affiliation: Ontario Cancer Institute and Campbell Family Institute for Cancer Research, Princess Margaret Cancer Centre, Toronto, ON, Canada.|Radiation Medicine Program, Princess Margaret Cancer Centre, Toronto, ON, Canada.|Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada.
authors.forename: Bradly
authors.initials: B
authors.lastname: Wouters
authors.affiliation: Princess Margaret Cancer Centre and MacFeeters-Hamilton Centre for Neuro-Oncology Research, Toronto, ON, Canada.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Aldape
authors.affiliation: Princess Margaret Cancer Centre and MacFeeters-Hamilton Centre for Neuro-Oncology Research, Toronto, ON, Canada.|Department of Neurosurgery, Toronto Western Hospital, University Health Network, 4W-436, Toronto, ON, Canada.
authors.forename: Gelareh
authors.initials: G
authors.lastname: Zadeh
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology / Q000532:radiotherapy; D063646:Carcinogenesis / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D053487:DEAD-box RNA Helicases / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D005909:Glioblastoma / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology / Q000532:radiotherapy; D006801:Humans; D008279:Magnetic Resonance Imaging; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D035683:MicroRNAs / Q000235:genetics*; D014411:Neoplastic Stem Cells / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering; D043244:Ribonuclease III / Q000235:genetics / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays
chemical_list: D035683:MicroRNAs; D034741:RNA, Small Interfering; C408087:DICER1 protein, human; D043244:Ribonuclease III; D053487:DEAD-box RNA Helicases
keywords: DICER; GSC; glioblastoma (GB); miRNA; radiation resistance