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Role of MacroH2A2 in the glioblastoma stem cell epigenome

机译:Macroh2a2在胶质母细胞瘤干细胞外观蛋白酶中的作用

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摘要

Glioblastoma is the most common primary malignant brain tumour in adults, and remains uniformly lethal. These tumours contain a subpopulation of glioblastoma stem cells (GSCs) that drive tumour recurrence and drug resistance. We find that MacroH2A2 is a histone variant that can stratify glioblastoma patients, with higher levels of this histone variant associated with better patient prognosis. Knockdown of macroH2A2 in GSCs is associated with increased self-renewal and an increased expression of stemness genes by RNA-seq. Our preliminary results suggest that macroH2A2 is a novel biomarker for glioblastoma and that macroH2A2 loss is a marker of GSC stemness and a poor prognostic marker in glioblastoma. This work identifies loss of macroH2A2 as a feature of GSCs and provides a framework for therapeutic modulation of this histone variant.
机译:胶质母细胞瘤是成人中最常见的原发性恶性脑肿瘤,并且仍然致死。 这些肿瘤含有胶质母细胞瘤干细胞(GSCs)的亚群,其驱动肿瘤复发和耐药性。 我们发现宏观2A2是一种组蛋白变体,可以分层胶质母细胞瘤患者,该组蛋白变异较高,与更好的患者预后相关。 GSC中的MacroH2A2敲低与RNA-SEQ的自我更新和茎秆基因的表达增加相关。 我们的初步结果表明,Macroh2a2是一种用于胶质母细胞瘤的新型生物标志物,并且Macroh2a2损失是GSC茎的标志物和胶质母细胞瘤中的差的预后标志物。 该工作识别宏观2A2的损失作为GSC的特征,并提供了该组蛋白变体的治疗调节的框架。

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