title: Pro-neural miR-128 is a glioma tumor suppressor that targets mitogenic kinases.
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.
authors.affiliation: Neuroscience Research Institute, University of California at Santa Barbara, Santa Barbara, CA, USA.
authors.forename: T
authors.initials: T
authors.lastname: Papagiannakopoulos
authors.forename: D
authors.initials: D
authors.lastname: Friedmann-Morvinski
authors.forename: P
authors.initials: P
authors.lastname: Neveu
authors.forename: J C
authors.initials: JC
authors.lastname: Dugas
authors.forename: R M
authors.initials: RM
authors.lastname: Gill
authors.forename: E
authors.initials: E
authors.lastname: Huillard
authors.forename: C
authors.initials: C
authors.lastname: Liu
authors.forename: H
authors.initials: H
authors.lastname: Zong
authors.forename: D H
authors.initials: DH
authors.lastname: Rowitch
authors.forename: B A
authors.initials: BA
authors.lastname: Barres
authors.forename: I M
authors.initials: IM
authors.lastname: Verma
authors.forename: K S
authors.initials: KS
authors.lastname: Kosik
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000235:genetics*; D002454:Cell Differentiation / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic; D015536:Down-Regulation; D066246:ErbB Receptors / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D005910:Glioma / Q000235:genetics*; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D016513:Mice, SCID; D035683:MicroRNAs / Q000502:physiology*; D058953:Neural Stem Cells / Q000502:physiology; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000235:genetics*
chemical_list: C545189:MIRN128 microRNA, human; D035683:MicroRNAs; C512478:EGFR protein, human; D066246:ErbB Receptors; D020796:Receptor, Platelet-Derived Growth Factor alpha