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SETMAR isoforms in glioblastoma: A matter of protein stability

2016; Impact Journals LLC; Volume: 8; Issue: 6 Linguagem: Inglês

10.18632/oncotarget.14218

1949-2553

Audrey Dussaussois-Montagne, Jérôme Jaillet, Laetitia Babin, Pierre Verrelle, Lucie Karayan‐Tapon, Sylvaine Renault, Cécilia Rousselot-Denis, Ilyess Zemmoura, Corinne Augé‐Gouillou,

RNA Interference and Gene Delivery

// Audrey Dussaussois-Montagne 1 , Jérôme Jaillet 1 , Laetitia Babin 1, 2 , Pierre Verrelle 3, 4, 5 , Lucie Karayan-Tapon 6, 7, 8 , Sylvaine Renault 1 , Cécilia Rousselot-Denis 9 , Ilyess Zemmoura 10, 11 , Corinne Augé-Gouillou 1 1 EA 6306 IGC, University François Rabelais, 37200 Tours, France 2 UMR CNRS 7292 GICC, University François Rabelais, 37000 Tours, France 3 EA 7283 CREaT, Université d′Auvergne, BP 10448, 63000 Clermont-Ferrand, France 4 Institut Curie, Dpt d'Oncologie Radiothérapique, 75005 Paris, France 5 Centre Jean Perrin, Service Radiothérapie, Laboratoire de Radio-Oncologie Expérimentale, 63000 Clermont-Ferrand, France 6 INSERM U1084, Laboratoire de Neurosciences Expérimentales et Cliniques, F-86021 Poitiers, France 7 University of Poitiers, F-86022 Poitiers, France 8 CHU of Poitiers, Laboratoire de Cancérologie Biologique, F-86021 Poitiers, France 9 CHRU of Tours, Unité d'Anatomie et Cytologie Pathologiques, 37000 Tours, France 10 INSERM U930 Imagerie & Cerveau, University François Rabelais, 37000 Tours, France 11 CHRU of Tours, Service de Neurochirurgie, 37000 Tours, France Correspondence to: Corinne Augé-Gouillou, email: auge@univ-tours.fr Keywords: glioblastoma, SETMAR, alternative ATG, protein half-live, NHEJ repair Received: April 15, 2016 Accepted: December 05, 2016 Published: December 25, 2016 ABSTRACT Glioblastomas (GBMs) are the most frequent and the most aggressive brain tumors, known for their chemo- and radio-resistance, making them often incurable. We also know that SETMAR is a protein involved in chromatin dynamics and genome plasticity, of which overexpression confers chemo- and radio-resistance to some tumors. The relationships between SETMAR and GBM have never been explored. To fill this gap, we define the SETMAR status of 44 resected tumors and of GBM derived cells, at both the mRNA and the protein levels. We identify a new, small SETMAR protein (so called SETMAR-1200), enriched in GBMs and GBM stem cells as compared to the regular enzyme (SETMAR-2100). We show that SETMAR-1200 is able to increase DNA repair by non-homologous end-joining, albeit with a lower efficiency than the regular SETMAR protein. Interestingly, the regular/small ratio of SETMAR in GBM cells changes depending on cell type, providing evidence that SETMAR expression is regulated by alternative splicing. We also demonstrate that SETMAR expression can be regulated by the use of an alternative ATG. In conclusion, various SETMAR proteins can be synthesized in human GBM that may each have specific biophysical and/or biochemical properties and characteristics. Among them, the small SETMAR may play a role in GBMs biogenesis. On this basis, we would like to consider SETMAR-1200 as a new potential therapeutic target to investigate, in addition to the regular SETMAR protein already considered by others.