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mA 表观转录组在胶质母细胞瘤中的调控作用研究进展。

Insights into the Regulatory Role of mA Epitranscriptome in Glioblastoma.

机构信息

Department of Biomedicine and Prevention, University of Rome Tor Vergata, Via Montpellier, 1 00133 Rome, Italy.

出版信息

Int J Mol Sci. 2020 Apr 17;21(8):2816. doi: 10.3390/ijms21082816.

Abstract

N-methyladenosine (mA) is one of the most widespread and abundant internal messenger RNA modifications found in eukaryotes. Emerging evidence suggests that this modification is strongly linked to the activation and inhibition of cancer pathways and is associated with prognostically significant tumour subtypes. The present review describes the dynamic nature of mA regulator enzymes, as methyltransferases, demethylases and mA binding proteins, and points out thevalue of the balance among these proteins in regulating gene expression, cell metabolism and cancer development. The main focus of this review is on the roles of mA modification in glioblastoma, the most aggressive and invariably lethal brain tumour. Although the study of mA in glioblastoma is a young one, and papers in this field can yield divergent conclusions, the results collected so far clearly demonstrate that modulation of mRNA mA levels impacts multiple aspects of this tumour, including growth, glioma stem cells self-renewal, and tumorigenesis, suggesting that mRNA mA modification may serve as a promising target for glioblastoma therapy. We also present recent data about another type of epitranscriptomic modification, the methylation of cytosine at a specific site of 28S rRNA, as it was recently shown to affect the biology of glioma cells, with high potential of clinical implications.

摘要

N6-甲基腺苷(m6A)是真核生物中发现的最广泛和丰富的内部信使 RNA 修饰之一。新出现的证据表明,这种修饰与癌症途径的激活和抑制密切相关,并与具有预后意义的肿瘤亚型相关。本综述描述了 m6A 调节酶(如甲基转移酶、去甲基酶和 m6A 结合蛋白)的动态性质,并指出了这些蛋白质之间平衡在调节基因表达、细胞代谢和癌症发展中的重要价值。本综述的主要重点是 m6A 修饰在胶质母细胞瘤中的作用,这是最具侵袭性和致命性的脑肿瘤。尽管 m6A 在胶质母细胞瘤中的研究还很年轻,该领域的论文可能会得出不同的结论,但迄今为止收集的结果清楚地表明,mRNA m6A 水平的调节会影响这种肿瘤的多个方面,包括生长、神经胶质瘤干细胞自我更新和肿瘤发生,这表明 mRNA m6A 修饰可能成为胶质母细胞瘤治疗的一个有前途的靶点。我们还介绍了最近关于另一种外转录组修饰(28S rRNA 特定位点胞嘧啶甲基化)的研究数据,因为最近的研究表明它会影响神经胶质瘤细胞的生物学特性,具有很高的临床应用潜力。

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