Tumorigenic Potential of miR-18A* in Glioma Initiating Cells Requires NOTCH-1 Signaling. - CNRS - Centre national de la recherche scientifique Accéder directement au contenu
Article Dans Une Revue Stem Cells / Stem Cells (Miamisburg) Année : 2013

Tumorigenic Potential of miR-18A* in Glioma Initiating Cells Requires NOTCH-1 Signaling.

Laurent Turchi
David N Debruyne
  • Fonction : Auteur
Fabien Almairac
  • Fonction : Auteur
Mohamed Fareh
  • Fonction : Auteur
Yasmine Neirijnck
Fanny Burel-Vandenbos
  • Fonction : Auteur
Philippe Paquis
  • Fonction : Auteur
Marie-Pierre Junier
Hervé Chneiweiss
  • Fonction : Auteur

Résumé

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 feedforward 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.

Dates et versions

hal-00811588 , version 1 (10-04-2013)

Identifiants

Citer

Laurent Turchi, David N Debruyne, Fabien Almairac, Virginie Virolle, Mohamed Fareh, et al.. Tumorigenic Potential of miR-18A* in Glioma Initiating Cells Requires NOTCH-1 Signaling.. Stem Cells / Stem Cells (Miamisburg), 2013, epub ahead of print. ⟨10.1002/stem.1373⟩. ⟨hal-00811588⟩
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