M Fareh

Publications (2)16.48 Total impact

• Source

  Available from: Thierry Virolle

  Article: The miR 302-367 cluster drastically affects self-renewal and infiltration properties of glioma-initiating cells through CXCR4 repression and consequent disruption of the SHH-GLI-NANOG network.

  M Fareh, L Turchi, V Virolle, D Debruyne, F Almairac, S de-la-Forest Divonne, P Paquis, O Preynat-Seauve, K-H Krause, H Chneiweiss, T Virolle
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  ABSTRACT: Glioblastoma multiforme (GBM) is the most common form of primary brain tumor in adults, often characterized by poor survival. Glioma-initiating cells (GiCs) are defined by their extensive self-renewal, differentiation, and tumor initiation properties. GiCs are known to be involved in tumor growth and recurrence, and in resistance to conventional treatments. One strategy to efficiently target GiCs in GBM consists in suppressing their stemness and consequently their tumorigenic properties. In this study, we show that the miR-302-367 cluster is strongly induced during serum-mediated stemness suppression. Stable miR-302-367 cluster expression is sufficient to suppress the stemness signature, self-renewal, and cell infiltration within a host brain tissue, through inhibition of the CXCR4 pathway. Furthermore, inhibition of CXCR4 leads to the disruption of the sonic hedgehog (SHH)-GLI-NANOG network, which is involved in self-renewal and expression of the embryonic stem cell-like signature. In conclusion, we demonstrated that the miR-302-367 cluster is able to efficiently trigger a cascade of inhibitory events leading to the disruption of GiCs stem-like and tumorigenic properties.
  Cell death and differentiation 07/2011; 19(2):232-44. · 8.24 Impact Factor
• Article: ATF3 and p15PAF are novel gatekeepers of genomic integrity upon UV stress.

  L Turchi, M Fareh, E Aberdam, S Kitajima, F Simpson, C Wicking, D Aberdam, T Virolle
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  ABSTRACT: After genotoxic stress, normal cells trigger DNA repair or, if unable to repair, undergo apoptosis to eradicate the cells that bear the risk of becoming tumorigenic. Here we show that repression of the transcription factor, activating transcription factor 3 (ATF3), after ultraviolet (UV)-mediated genotoxic stress impairs the DNA repair process. We provide evidence that ATF3 directly regulates the proliferating cell nuclear antigen (PCNA)-associated factor KIAA0101/p15(PAF). We further show that the expressions of ATF3 and p15(PAF) is sufficient to trigger the DNA repair machinery, and that attenuation of their expression alters DNA repair mechanisms. We show that the expression of p15(PAF) compensates for a lack of ATF3 expression, thereby constituting a major effector of ATF3 in the DNA repair process. In addition, we provide evidence that p15(PAF) expression is required for the correct function of PCNA during DNA repair, as prevention of their interaction significantly alters DNA repair mechanisms. Finally, defective DNA repair, because of the downregulation of p15(PAF) expression, rendered the cells more sensitive to UV-induced cell death. Therefore, our results suggest ATF3 and p15(PAF) as novel gatekeepers of genomic integrity after UV exposure.
  Cell death and differentiation 03/2009; 16(5):728-37. · 8.24 Impact Factor