Ianniello Zaira, Paiardini Alessandro, Fatica Alessandro
Department of Biology and Biotechnology "Charles Darwin," Sapienza University of Rome, Rome, Italy.
Department of Biochemical Sciences "A. Rossi Fanelli," Sapienza University of Rome, Rome, Italy.
Front Oncol. 2019 Apr 9;9:251. doi: 10.3389/fonc.2019.00251. eCollection 2019.
Recent studies have uncovered an important role for RNA modifications in gene expression regulation, which led to the birth of the epitranscriptomics field. It is now acknowledged that RNA modifiers play a crucial role in the control of differentiation of stem and progenitor cells and that changes in their levels are a relevant feature of different types of cancer. To date, among more than 160 different RNA chemical modifications, the more relevant in cancer biology is the reversible and dynamic N-methylation of adenosine, yielding N-methyladenosine (mA). mA is the more abundant internal modification in mRNA, regulating the expression of the latter at different levels, from maturation to translation. Here, we will describe the emerging role of mA modification in acute myeloid leukemia (AML), which, among first, has demonstrated how mis-regulation of the m6A modifying system can contribute to the development and progression of cancer. Moreover, we will discuss how AML is paving the way to the development of new therapeutic options based on the inhibition of mA deposition.
最近的研究揭示了RNA修饰在基因表达调控中的重要作用，这催生了表观转录组学领域。现在人们认识到，RNA修饰因子在干细胞和祖细胞的分化控制中起着关键作用，并且它们水平的变化是不同类型癌症的一个相关特征。迄今为止，在160多种不同的RNA化学修饰中，在癌症生物学中更相关的是腺苷的可逆性动态N-甲基化，产生N-甲基腺苷（m⁶A）。m⁶A是mRNA中含量更丰富的内部修饰，在从成熟到翻译的不同水平上调节mRNA的表达。在这里，我们将描述m⁶A修饰在急性髓系白血病（AML）中的新作用，首先，AML已经证明了m⁶A修饰系统的失调如何促进癌症的发生和发展。此外，我们将讨论AML如何为基于抑制m⁶A沉积的新治疗选择的开发铺平道路。
