Analyse fonctionnelle des miRNA impliqués dans le contrôle de la plasticité des cellules souches neuronales cancéreuses – GLIOMIRSTEM

Glioblastomas are the most common form of primary brain tumors in adults. Therapeutic options are limited and survival do not exceed 15 months. The poor prognosis of this cancer is explained by the recurrence of tumors due to the presence of cancer stem cells (CSC). Differentiated tumor cells are sensitive to therapies and die but CSC are resistant and the tumor recurs due to their proliferation and selfrenewal properties. Therefore, to improve efficiencies of current treatments it is necessary to trigger CSC by inhbiting their selfrenewal and forcing them to differentiate. Consequently, it is of great importance to better comprehend the mechanisms that control the regulation of neuronal normal and cancer stem cell plasticity. We have a model of cancer neuronal stem cells derived from high grade glioblastomas. We have identified the culture conditions that enable not only CSC differentiation but also the reprogrammation in CSC of neo differentiated tumor cells. We have performed a microRNA profiling (600 miR) during CSC differentiation. Among the 20 micro-RNA stably up or downregulated upon 8 days of differentiation, we have begun the functional study by focussing on a cluster of miR (cluster X) not detected in CSC and only expressed in the differentiated cells. Expression of this cluster in CSC induced inhibition of not only stemness markers expression but also the bad tumor prognostic marker CXCR4. On the basis of these excisting first results, our aim is to identify and characterize the function and the putative therapeutic interest of miR involved in the control of CSC plasticity.