文章：

RNA N6 -甲基腺苷修饰在实体瘤中的应用：新的治疗前沿

RNA N6-methyladenosine modification in solid tumors: new therapeutic frontiers

原文发布日期：2020-01-20

英文摘要：

Epigenetic mRNA modification is an evolving field. N6-methyladenosine (m6A) is the most frequent internal transcriptional modification in eukaryotic messenger RNAs (mRNAs). This review will discuss the functions of the m6A mRNA machinery, including its “writers” that are components of the methyltransferase complex, its “readers” and its “erasers” (specifically FTO and ALKBH5) in cancer. The writers deposit the m6A and include METTL3, METTL14, WTAP, VIRMA, and RBM15. M6A methylation is removed by the m6A demethylases (FTO and ALKBH5). Lastly, the most diverse members are the readers that can contribute to mRNA splicing, stability, translation, and nuclear export. Many of these functions continue to be elucidated. The dysregulation of this machinery in various malignancies and the associated impact on tumorigenesis and drug response will be discussed herein with a focus on solid tumors. It is clear that, by contributing to either mRNA stability or translation, there are downstream targets that are impacted, contributing to cancer progression and the self-renewal ability of cancer stem cells. 

摘要翻译： 

表观遗传学mRNA修饰是一个不断发展的研究领域。N6-甲基腺苷（m6A）是真核信使RNA（mRNA）中最常见的内部转录修饰。本综述将探讨m6A mRNA调控机制在癌症中的作用，包括甲基转移酶复合物组成的"书写蛋白"（如METTL3、METTL14、WTAP、VIRMA和RBM15）、"阅读蛋白"以及"擦除蛋白"（特指FTO和ALKBH5）。书写蛋白负责沉积m6A修饰，而m6A去甲基化酶（FTO和ALKBH5）则负责去除该修饰。最后，功能最多样的阅读蛋白可参与mRNA剪接、稳定性调控、翻译过程及核输出等功能——这些功能的多样性仍在不断被揭示。本文重点讨论实体肿瘤中该调控机制在多种恶性肿瘤中的失调现象，及其对肿瘤发生和药物反应的影响。通过调节mRNA稳定性或翻译过程，m6A修饰显然会影响下游靶标，从而促进癌症进展和癌症干细胞自我更新能力的维持。

原文链接：

RNA N6-methyladenosine modification in solid tumors: new therapeutic frontiers