Research Center for Functional Genomics, Biomedicine and Translational Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, 400337 Cluj-Napoca, Romania.
Department of Microbiology, Oslo University Hospital, 0424 Oslo, Norway.
Int J Mol Sci. 2023 Nov 14;24(22):16320. doi: 10.3390/ijms242216320.
Glioblastoma (GBM) is a primary brain tumor arising from glial cells. The tumor is highly aggressive, the reason for which it has become the deadliest brain tumor type with the poorest prognosis. Like other cancers, it compromises molecular alteration on genetic and epigenetic levels. Epigenetics refers to changes in gene expression or cellular phenotype without the occurrence of any genetic mutations or DNA sequence alterations in the driver tumor-related genes. These epigenetic changes are reversible, making them convenient targets in cancer therapy. Therefore, we aim to review critical epigenetic dysregulation processes in glioblastoma. We will highlight the significant affected tumor-related pathways and their outcomes, such as regulation of cell cycle progression, cell growth, apoptosis, angiogenesis, cell invasiveness, immune evasion, or acquirement of drug resistance. Examples of molecular changes induced by epigenetic modifications, such as DNA epigenetic alterations, histone post-translational modifications (PTMs), and non-coding RNA (ncRNA) regulation, are highlighted. As understanding the role of epigenetic regulators and underlying molecular mechanisms in the overall pro-tumorigenic landscape of glioblastoma is essential, this literature study will provide valuable insights for establishing the prognostic or diagnostic value of various non-coding transcripts, including miRNAs.
胶质母细胞瘤(GBM)是一种起源于神经胶质细胞的原发性脑肿瘤。这种肿瘤具有高度侵袭性,是导致其成为最致命的脑肿瘤类型和预后最差的原因。与其他癌症一样,它在遗传和表观遗传层面上存在分子改变。表观遗传学是指在不发生驱动肿瘤相关基因的任何基因突变或 DNA 序列改变的情况下,基因表达或细胞表型的变化。这些表观遗传变化是可逆的,使其成为癌症治疗的便利靶点。因此,我们旨在综述胶质母细胞瘤中关键的表观遗传失调过程。我们将重点介绍受影响的重要肿瘤相关途径及其结果,如细胞周期进程、细胞生长、细胞凋亡、血管生成、细胞侵袭、免疫逃逸或获得耐药性的调节。还强调了由表观遗传修饰诱导的分子变化的例子,如 DNA 表观遗传改变、组蛋白翻译后修饰(PTMs)和非编码 RNA(ncRNA)的调节。由于了解表观遗传调节剂在胶质母细胞瘤整体促肿瘤发生景观中的作用及其潜在的分子机制至关重要,因此这项文献研究将为确定各种非编码转录物(包括 miRNA)的预后或诊断价值提供有价值的见解。
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