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

Sheila Mansouri; Sanjay Singh; Amir Alamsahebpour; Kelly Burrell; Mira Li; Merve Karabork; Can Ekinci; Elizabeth Koch; Ihsan Solaroglu; Jeffery T. Chang; Bradly Wouters; Kenneth Aldape; Gelareh Zadeh

doi:10.18632/oncotarget.10570

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Research Papers:

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

Sheila Mansouri, Sanjay Singh, Amir Alamsahebpour, Kelly Burrell, Mira Li, Merve Karabork, Can Ekinci, Elizabeth Koch, Ihsan Solaroglu, Jeffery T. Chang, Bradly Wouters, Kenneth Aldape and Gelareh Zadeh _

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Oncotarget. 2016; 7:56431-56446. https://doi.org/10.18632/oncotarget.10570

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Abstract

Sheila Mansouri1,*, Sanjay Singh1,*, Amir Alamsahebpour1, Kelly Burrell1, Mira Li1, Merve Karabork2, Can Ekinci2, Elizabeth Koch5,7, Ihsan Solaroglu2,3, Jeffery T. Chang4, Bradly Wouters5,6,7, Kenneth Aldape1, Gelareh Zadeh1,8

1Princess Margaret Cancer Centre and MacFeeters-Hamilton Centre for Neuro-Oncology Research, Toronto, ON, Canada

2School of Medicine, Koç University, Rumelifeneri Yolu, Sariyer, Istanbul, Turkey

3Loma Linda University, School of Medicine, Loma Linda, CA, USA

4Department of Integrative Biology and Pharmacology, McGovern Medical School, University of Texas, Houston, TX, USA

5Ontario Cancer Institute and Campbell Family Institute for Cancer Research, Princess Margaret Cancer Centre, Toronto, ON, Canada

6Radiation Medicine Program, Princess Margaret Cancer Centre, Toronto, ON, Canada

7Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada

8Department 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: [email protected]

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.

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Research Papers:

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

Abstract