Tumorigenic Potential of miR‐18A* in Glioma Initiating Cells Requires NOTCH‐1 Signaling123. (5th July 2013)

• Record Type: Journal Article
• Authors: Turchi, Laurent; Debruyne, David N.; Almairac, Fabien; Virolle, Virginie; Fareh, Mohamed; Neirijnck, Yasmine; Burel‐Vandenbos, Fanny; Paquis, Philippe; Junier, Marie‐Pierre; Van Obberghen‐Schilling, Ellen; Chneiweiss, Hervé; Virolle, Thierry
• Is Part Of: Stem cells. Volume 31:Number 7(2013:Jul.)
• Page Start: 1252
• Page End: 1265
• Publication Date: 2013-07-05
• Subjects: Cloning -- Periodicals; Clone cells -- Periodicals; Stem cells -- Periodicals; Cell Differentiation -- Periodicals; Cell Division -- Periodicals; Clone Cells -- Periodicals; Hematopoietic Stem Cells -- Periodicals; Stem Cells -- Periodicals; 571.84
• DOI: 10.1002/stem.1373
• Languages: English
• ISSNs: 1066-5099

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <p>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. S<sc>TEM</sc> C<sc>ells</sc><italic>2013;31:1252–1265</italic></p> </abstract>