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Cancer Stem Cells
Article first published online: 5 JUL 2013
Copyright © 2013 AlphaMed Press
Volume 31, Issue 7, pages 1252–1265, July 2013
How to Cite
Turchi, L., Debruyne, D. N., Almairac, F., Virolle, V., Fareh, M., Neirijnck, Y., Burel-Vandenbos, F., Paquis, P., Junier, M.-P., Van Obberghen-Schilling, E., Chneiweiss, H. and Virolle, T. (2013), Tumorigenic Potential of miR-18A* in Glioma Initiating Cells Requires NOTCH-1 Signaling. STEM CELLS, 31: 1252–1265. doi: 10.1002/stem.1373
Author contributions: L.T. : conception and design, manuscript writing, data analysis and interpretation, and collection and or assembly of data; D.N.D.: conception and design, data analysis and interpretation, and collection and or assembly of data; F.A., V.V., M. F., and Y.N.: conception and design and data analysis and interpretation; F.B. and M.J.: provision of study material of patients and data analysis and interpretation; P.P.: provision of study material of patients; E.V.O.: manuscript writing; H.C.: provision of study material of patients and manuscript writing; T. V.: conception and design, manuscript writing, data analysis and interpretation, collection and or assembly of data, and final approval of manuscript.
Disclosure of potential conflicts of interest is found at the end of this article.
first published online in STEM CELLS EXPRESS March 26, 2013.
- Issue published online: 5 JUL 2013
- Article first published online: 5 JUL 2013
- Accepted manuscript online: 26 MAR 2013 08:22AM EST
- Manuscript Accepted: 28 FEB 2013
- Manuscript Received: 24 SEP 2012
- Association pour la Recherche sur le Cancer. Grant Number: subvention 3161
- Association Sauvons Laura
- Agence Nationale pour la Recherche
- ANR Jeunes Chercheurs
- Fondation de France, ARC projet, INSERM, UNSA
- Delta like 3 protein;
- Sonic hedgehog;
- Extracellular signal-regulated kinase
Stem cell-like properties of glioma initiating cells (GiCs) fuel glioblastoma (GBM) development by providing the different cell types that comprise the tumor. It is therefore likely that the molecular circuitries that regulate their decision to self-renew or commit to a more differentiated state may offer targets for future innovative therapies. In previous micro-RNA profiling studies to search for regulators of stem cell plasticity, we identified miR-18a* as a potential candidate and its expression correlated with the stemness state. Here, using human GiCs we found that miR-18a* expression promotes clonal proliferation in vitro and tumorigenicity in vivo. Mechanistically, ERK-dependent induction of miR-18a* directly represses expression of DLL3, an autocrine inhibitor of NOTCH, thus enhancing the level of activated NOTCH-1. Activated NOTCH-1 in turn is required for sustained ERK activation. This feed-forward loop, driven by miR-18a*, is required to turn on the SHH-GLI-NANOG network, essential for GiC self-renewal. Hence, by tightly regulating expression of DLL3, miR-18a* constitutes an important signaling mediator for fine tuning the level of GiC self-renewal. STEM Cells2013;31:1252–1265