Université Clermont Auvergne, CNRS, Inserm, GReD, F-63000 Clermont-Ferrand, France.
ProDiCeT UR 24144, Université de Poitiers, F-86000 Poitiers, France.
Int J Mol Sci. 2022 Apr 25;23(9):4743. doi: 10.3390/ijms23094743.
Glioblastomas represent approximatively half of all gliomas and are the most deadly and aggressive form. Their therapeutic resistance and tumor relapse rely on a subpopulation of cells that are called Glioma Stem Cells (GSCs). Here, we investigated the role of the long non-coding RNA in GSC biology using descriptive and functional analyses of glioma samples classified according to their isocitrate dehydrogenase () gene mutation status, and of GSC lines. We found that is overexpressed only in aggressive () glioma and GSC lines. ShRNA-based depletion of in GSCs decreased cell proliferation and altered the expression of several hundreds of genes. Integrative analysis revealed that these expression changes were not associated with changes in DNA methylation or chromatin signatures at the promoter of the majority of genes deregulated following silencing in GSCs, suggesting a post-transcriptional regulation. In addition, transcription factor binding motif enrichment and correlation analyses indicated that affects, directly or indirectly, the expression of key transcription factors implicated in GCS biology, including E2F8, E2F1, STAT1, and ATF3, thus contributing to GCS aggressiveness by promoting their proliferation and modulating the inflammation pathway.
胶质母细胞瘤约占所有神经胶质瘤的一半，是最致命和侵袭性的形式。它们的治疗耐药性和肿瘤复发依赖于被称为神经胶质瘤干细胞（GSCs）的细胞亚群。在这里，我们使用根据异柠檬酸脱氢酶（）基因突变状态分类的神经胶质瘤样本和 GSC 系进行描述性和功能分析，研究了长非编码 RNA 在 GSC 生物学中的作用。我们发现，仅在侵袭性（）神经胶质瘤和 GSC 系中过表达。在 GSCs 中基于 shRNA 的 耗竭降低了细胞增殖并改变了数百个基因的表达。综合分析表明，这些表达变化与大多数基因启动子处的 DNA 甲基化或染色质特征的变化无关，这些基因在 GSCs 中沉默后被下调，这表明存在转录后调控。此外，转录因子结合基序富集和相关分析表明，直接或间接影响 GCS 生物学中关键转录因子的表达，包括 E2F8、E2F1、STAT1 和 ATF3，从而通过促进其增殖和调节炎症途径来促进 GCS 的侵袭性。
