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Pro-neural miR-128 is a glioma tumor suppressor that targets mitogenic kinases.
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| Author |
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 |
| Citation Information |
Oncogene, 31: (2012) |
| Keywords |
Animals,Brain Neoplasms,Cell Differentiation,Cell Line, Tumor,Cell Proliferation,Cell Transformation, Neoplastic,Down-Regulation,Gene Expression Regulation, Neoplastic,Genes, Tumor Suppressor,Glioma,Humans,Mice,Mice, Nude,Mice, SCID,MicroRNAs,Neural Stem Cells,Receptor, Epidermal Growth Factor,Receptor, Platelet-Derived Growth Factor alpha |
| Related Products |
05-1050 |
| Pub Med ID |
21874051 |
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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.
