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  • Pro-neural miR-128 is a glioma tumor suppressor that targets mitogenic kinases.

Pro-neural miR-128 is a glioma tumor suppressor that targets mitogenic kinases.

Oncogene (2011-08-30)
T Papagiannakopoulos, D Friedmann-Morvinski, P Neveu, J C Dugas, R M Gill, E Huillard, C Liu, H Zong, D H Rowitch, B A Barres, I M Verma, K S Kosik
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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Anti-Glial Fibrillary Acidic Protein (GFAP)−Cy3 antibody, Mouse monoclonal, clone G-A-5, purified from hybridoma cell culture
Sigma-Aldrich
4G10® Platinum, Anti-Phosphotyrosine Antibody (mouse monoclonal cocktail IgG2b), clone 4G10®, Upstate®, from mouse