Deacon Simon, Walker Lauryn, Radhi Masar, Smith Stuart
Children's Brain Tumour Research Centre, University of Nottingham, Nottingham NG7 2RD, UK.
Nottingham University Hospitals NHS Trust, Nottingham NG7 2UH, UK.
Cancers (Basel). 2023 Jun 23;15(13):3307. doi: 10.3390/cancers15133307.
Glioblastoma is the most prevalent primary brain tumour and invariably confers a poor prognosis. The immense intra-tumoral heterogeneity of glioblastoma and its ability to rapidly develop treatment resistance are key barriers to successful therapy. As such, there is an urgent need for the greater understanding of the tumour biology in order to guide the development of novel therapeutics in this field. N6-methyladenosine (m6A) is the most abundant of the RNA modifications in eukaryotes. Studies have demonstrated that the regulation of this RNA modification is altered in glioblastoma and may serve to regulate diverse mechanisms including glioma stem-cell self-renewal, tumorigenesis, invasion and treatment evasion. However, the precise mechanisms by which m6A modifications exert their functional effects are poorly understood. This review summarises the evidence for the disordered regulation of m6A in glioblastoma and discusses the downstream functional effects of m6A modification on RNA fate. The wide-ranging biological consequences of m6A modification raises the hope that novel cancer therapies can be targeted against this mechanism.
胶质母细胞瘤是最常见的原发性脑肿瘤,预后通常很差。胶质母细胞瘤巨大的肿瘤内异质性及其快速产生治疗抗性的能力是成功治疗的关键障碍。因此,迫切需要更深入地了解肿瘤生物学,以指导该领域新型治疗方法的开发。N6-甲基腺苷(m6A)是真核生物中最丰富的RNA修饰。研究表明,这种RNA修饰的调控在胶质母细胞瘤中发生改变,可能用于调节多种机制,包括胶质瘤干细胞自我更新、肿瘤发生、侵袭和逃避治疗。然而,m6A修饰发挥其功能作用的确切机制尚不清楚。本综述总结了胶质母细胞瘤中m6A调控紊乱的证据,并讨论了m6A修饰对RNA命运的下游功能影响。m6A修饰广泛的生物学后果带来了希望,即可以针对这一机制开发新型癌症治疗方法。