Inhibition of GPR158 by microRNA-449a suppresses neural lineage of glioma stem/progenitor cells and correlates with higher glioma grades.
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Date
2018-08-02ICR Author
Author
Li, N
Zhang, Y
Sidlauskas, K
Ellis, M
Evans, I
Frankel, P
Lau, J
El-Hassan, T
Guglielmi, L
Broni, J
Richard-Loendt, A
Brandner, S
Type
Journal Article
Metadata
Show full item recordAbstract
To identify biomarkers for glioma growth, invasion and progression, we used a candidate gene approach in mouse models with two complementary brain tumour phenotypes, developing either slow-growing, diffusely infiltrating gliomas or highly proliferative, non-invasive primitive neural tumours. In a microRNA screen we first identified microRNA-449a as most significantly differentially expressed between these two tumour types. miR-449a has a target dependent effect, inhibiting cell growth and migration by downregulation of CCND1 and suppressing neural phenotypes by inhibition of G protein coupled-receptor (GPR) 158. GPR158 promotes glioma stem cell differentiation and induces apoptosis and is highest expressed in the cerebral cortex and in oligodendrogliomas, lower in IDH mutant astrocytomas and lowest in the most malignant form of glioma, IDH wild-type glioblastoma. The correlation of GPR158 expression with molecular subtypes, patient survival and therapy response suggests a possible role of GPR158 as prognostic biomarker in human gliomas.
Collections
Subject
Cell Line, Tumor
Stem Cells
Animals
Humans
Mice
Glioma
Astrocytoma
Glioblastoma
Oligodendroglioma
Brain Neoplasms
Receptors, G-Protein-Coupled
Transcription Factors
MicroRNAs
Apoptosis
Cell Differentiation
Cell Proliferation
Cell Movement
Down-Regulation
Biomarkers, Tumor
Research team
Cancer Stem Cell
Language
eng
Date accepted
2018-03-28
License start date
2018-08
Citation
Oncogene, 2018, 37 (31), pp. 4313 - 4333
Publisher
NATURE PUBLISHING GROUP