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

DICER 控制胶质瘤干细胞的特征以及胶质母细胞瘤异种移植小鼠模型中由此产生的肿瘤

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作者: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

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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