Pro-neural miR-128 is a glioma tumor suppressor that targets mitogenic kinases
Open Access
- 29 August 2011
- journal article
- research article
- Published by Springer Science and Business Media LLC in Oncogene
- Vol. 31 (15), 1884-1895
- https://doi.org/10.1038/onc.2011.380
Abstract
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-α. 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.This publication has 39 references indexed in Scilit:
- Mosaic Analysis with Double Markers Reveals Tumor Cell of Origin in GliomaCell, 2011
- Modulation of K-Ras-Dependent Lung Tumorigenesis by MicroRNA-21Cancer Cell, 2010
- Integrated Genomic Analysis Identifies Clinically Relevant Subtypes of Glioblastoma Characterized by Abnormalities in PDGFRA, IDH1, EGFR, and NF1Cancer Cell, 2010
- Collagen VI protects neurons against Aβ toxicityNature Neuroscience, 2009
- Development of a novel mouse glioma model using lentiviral vectorsNature Medicine, 2009
- Comprehensive genomic characterization defines human glioblastoma genes and core pathwaysNature, 2008
- Glioma Stem Cells: A Midterm ExamNeuron, 2008
- Mechanisms of post-transcriptional regulation by microRNAs: are the answers in sight?Nature Reviews Genetics, 2008
- MicroRNA expression profiles classify human cancersNature, 2005
- Prediction of Mammalian MicroRNA TargetsCell, 2003