Journal
ONCOGENE
Volume 31, Issue 15, Pages 1884-1895Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/onc.2011.380
Keywords
microRNA; glioma stem cells; miR-128; EGFR; PDGFR alpha
Funding
- WM Keck Foundation
- Miriam and Sheldon Adelson Medical Foundation
- National Science Foundation [PHY05-51164]
- Myelin Repair Foundation
- National Multiple Sclerosis Society
- NIH [R55-CA136495, R01-CA136495]
- The Pew Charitable Trusts
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MicroRNAs (miRNAs) carry out post-transcriptional control of a multitude of cellular processes. Aberrant expression of miRNA can lead to diseases, including cancer. Gliomas are aggressive brain tumors that are thought to arise from transformed glioma-initiating neural stem cells (giNSCs). With the use of giNSCs and human glioblastoma cells, we investigated the function of miRNAs in gliomas. We identified pro-neuronal miR-128 as a candidate glioma tumor suppressor miRNA. Decreased expression of miR-128 correlates with aggressive human glioma subtypes. With a combination of molecular, cellular and in vivo approaches, we characterize miR-128's tumor suppressive role. miR-128 represses giNSC growth by enhancing neuronal differentiation. miR-128 represses growth and mediates differentiation by targeting oncogenic receptor tyrosine kinases (RTKs) epithelial growth factor receptor and platelet-derived growth factor receptor-alpha. Using an autochthonous glioma mouse model, we demonstrated that miR-128 repressed gliomagenesis. We identified miR-128 as a glioma tumor suppressor that targets RTK signaling to repress giNSC self-renewal and enhance differentiation. Oncogene (2012) 31, 1884-1895; doi:10.1038/onc.2011.380; published online 29 August 2011
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