Inhibition of GPR158 by microRNA-449a suppresses neural lineage of glioma stem/progenitor cells and correlates with higher glioma grades.
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Embargo End Date
ICR Authors
Authors
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
Zhang, Y
Sidlauskas, K
Ellis, M
Evans, I
Frankel, P
Lau, J
El-Hassan, T
Guglielmi, L
Broni, J
Richard-Loendt, A
Brandner, S
Document Type
Journal Article
Date
2018-08-02
Date Accepted
2018-03-28
Abstract
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.
Citation
Oncogene, 2018, 37 (31), pp. 4313 - 4333
Source Title
Publisher
NATURE PUBLISHING GROUP
ISSN
0950-9232
eISSN
1476-5594
Collections
Research Team
Cancer Stem Cell