EZH2-regulated DAB2IP is a medulloblastoma tumor suppressor and a positive marker for survival
Menée sur des bases de données d'expression de gènes et sur des lignées cellulaires, cette étude suggère que la protéine DAB2IP exerce une fonction de suppresseur de tumeurs dans les médulloblastomes
Purpose: Medulloblastoma is the most common malignant brain tumor in children. Despite recent improvements, the molecular mechanisms driving medulloblastoma are not fully understood and further elucidation could provide cues to improve outcome prediction and therapeutic approaches. Experimental Design: Here, we performed a meta-analysis of mouse and human medulloblastoma gene expression datasets, in order to identify potential medulloblastoma tumor suppressor genes. Results: We identified DAB2IP, a member of the RAS-GTPase activating protein family (RAS GAP), and demonstrated that DAB2IP expression is repressed in medulloblastoma by EZH2-induced trimethylation. Moreover, we observed that reduced DAB2IP expression correlates significantly with a poor overall survival of medulloblastoma patients, independent of metastatic stage. Finally, we demonstrated that ectopic DAB2IP expression enhances stress-induced apoptotis in medulloblastoma cells and that reduced expression of DAB2IP in medulloblastoma cells conveys resistance to irradiation-induced cell death. Conclusion: These results suggest that repression of DAB2IP may at least partly protect medulloblastoma cells from apoptotic cell death. Moreover, DAB2IP may represent a molecular marker to distinguish medulloblastoma patients at high risk from those with a longer survival prognosis.