Freire-Benéitez Verónica, Pomella Nicola, Millner Thomas O, Dumas Anaëlle A, Niklison-Chirou Maria Victoria, Maniati Eleni, Wang Jun, Rajeeve Vinothini, Cutillas Pedro, Marino Silvia
Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, E1 2AT, London, UK.
Barts Cancer Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London EC1M 6AS UK.
NAR Cancer. 2021 Mar 22;3(1):zcab009. doi: 10.1093/narcan/zcab009. eCollection 2021 Mar.
Glioblastoma (GBM) is the most common and aggressive intrinsic brain tumour in adults. Epigenetic mechanisms controlling normal brain development are often dysregulated in GBM. Among these, BMI1, a structural component of the Polycomb Repressive Complex 1 (PRC1), which promotes the H2AK119ub catalytic activity of Ring1B, is upregulated in GBM and its tumorigenic role has been shown and . Here, we have used protein and chromatin immunoprecipitation followed by mass spectrometry (MS) analysis to elucidate the protein composition of PRC1 in GBM and transcriptional silencing of defining interactors in primary patient-derived GIC lines to assess their functional impact on GBM biology. We identify novel regulatory functions in mRNA splicing and cholesterol transport which could represent novel targetable mechanisms in GBM.
胶质母细胞瘤（GBM）是成人中最常见且侵袭性最强的原发性脑肿瘤。控制正常脑发育的表观遗传机制在GBM中常常失调。其中，BMI1是多梳抑制复合体1（PRC1）的结构成分，可促进Ring1B的H2AK119ub催化活性，在GBM中上调，并且其致瘤作用已得到证实。在此，我们采用蛋白质和染色质免疫沉淀结合质谱（MS）分析来阐明GBM中PRC1的蛋白质组成，并对原发性患者来源的胶质母细胞瘤起始细胞（GIC）系中确定的相互作用分子进行转录沉默，以评估它们对GBM生物学的功能影响。我们确定了mRNA剪接和胆固醇转运中的新调控功能，这可能代表了GBM中新型的可靶向作用机制。
