DICER governs characteristics of glioma stem cells and the resulting tumors in xenograft mouse models of glioblastoma

// Sheila Mansouri 1, * , Sanjay Singh 1, * , Amir Alamsahebpour 1 , Kelly Burrell 1 , Mira Li 1 , Merve Karabork 2 , Can Ekinci 2 , Elizabeth Koch 5, 7 , Ihsan Solaroglu 2, 3 , Jeffery T. Chang 4 , Bradly Wouters 5, 6, 7 , Kenneth Aldape 1 , Gelareh Zadeh 1, 8 1 Princess Margaret Cancer Centre and MacFeeters-Hamilton Centre for Neuro-Oncology Research, Toronto, ON, Canada 2 School of Medicine, Koc University, Rumelifeneri Yolu, Sariyer, Istanbul, Turkey 3 Loma Linda University, School of Medicine, Loma Linda, CA, USA 4 Department of Integrative Biology and Pharmacology, McGovern Medical School, University of Texas, Houston, TX, USA 5 Ontario Cancer Institute and Campbell Family Institute for Cancer Research, Princess Margaret Cancer Centre, Toronto, ON, Canada 6 Radiation Medicine Program, Princess Margaret Cancer Centre, Toronto, ON, Canada 7 Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada 8 Department of Neurosurgery, Toronto Western Hospital, University Health Network, 4W-436, Toronto, ON, Canada * These authors have contributed equally to this work Correspondence to: Gelareh Zadeh, email: gelareh.zadeh@uhn.ca Keywords: GSC, glioblastoma (GB), DICER, miRNA, radiation resistance Received: March 17, 2016      Accepted: May 19, 2016      Published: July 13, 2016 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.