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

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

School of Medicine

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Pages (from-to)	56431-56446
Number of pages	16
Journal	Oncotarget
Volume	7
Issue number	35
DOIs	https://doi.org/10.18632/oncotarget.10570
State	Published - Aug 30 2016

ASJC Scopus Subject Areas

Oncology

Keywords

DICER
GSC
Glioblastoma (GB)
Radiation resistance
miRNA
MicroRNAs/genetics
Brain Neoplasms/diagnostic imaging
Ribonuclease III/genetics
Humans
Gene Expression Regulation, Neoplastic
DEAD-box RNA Helicases/genetics
Gene Knockdown Techniques
RNA Interference
Cell Proliferation/genetics
Neoplastic Stem Cells/metabolism
Mice, SCID
Glioblastoma/diagnostic imaging
Xenograft Model Antitumor Assays
Magnetic Resonance Imaging
Animals
Cell Line, Tumor
Cell Differentiation/genetics
Mice, Inbred NOD
Mice
RNA, Small Interfering
Carcinogenesis/genetics

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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.",

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

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AU - Mansouri, Sheila

AU - Singh, Sanjay

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AU - Burrell, Kelly

AU - Li, Mira

AU - Karabork, Merve

AU - Ekinci, Can

AU - Koch, Elizabeth

AU - Solaroglu, Ihsan

AU - Chang, Jeffery T.

AU - Wouters, Bradly

AU - Aldape, Kenneth

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AB - 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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KW - Magnetic Resonance Imaging

KW - Animals

KW - Cell Line, Tumor

KW - Cell Differentiation/genetics

KW - Mice, Inbred NOD

KW - Mice

KW - RNA, Small Interfering

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

Abstract

ASJC Scopus Subject Areas

Keywords

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