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- Title
Pro-neural miR-128 is a glioma tumor suppressor that targets mitogenic kinases.
- Authors
Papagiannakopoulos, T; Friedmann-Morvinski, D; Neveu, P; Dugas, J C; Gill, R M; Huillard, E; Liu, C; Zong, H; Rowitch, D H; Barres, B A; Verma, I M; Kosik, K S
- 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.
- Publication
Oncogene, 2012, Vol 31, Issue 15, p1884
- ISSN
1476-5594
- Publication type
Journal Article
- DOI
10.1038/onc.2011.380