急性髓系白血病中RNA修饰的异常调控及其靶向干预  

Aberrant Regulation and Targeting of RNA Modifications in Acute Myeloid Leukemia

作　　者：张速博 李垣佩 黄慧琳 ZHANG Subo;LI Yuanpei;HUANG Huilin(State Key Laboratory of Oncology in South China,Guangdong Provincial Clinical Research Center for Cancer,Sun Yat-sen University Cancer Center,Guangzhou 510060,China)

机构地区：[1]华南恶性肿瘤防治全国重点实验室,广东省恶性肿瘤临床医学研究中心,中山大学肿瘤防治中心,广州510060

出　　处：《中国细胞生物学学报》2025年第3期581-597,共17页Chinese Journal of Cell Biology

基　　金：国家自然科学基金(批准号:82470161、82201377、32400475);中国博士后创新人才支持计划(批准号:BX2021393);中国博士后科学基金(批准号:2022M723652、2024M753725);广州市科技计划(批准号:2024A04J6321);中山大学肿瘤防治中心青年人才提升计划(批准号:YTP-SYSUCC-0044)资助的课题。

摘　　要：急性髓系白血病(AML)是一种具有高度异质性的血液系统恶性肿瘤,其发病机制复杂,涉及多种表观遗传机制的异常调控。近年来,研究发现RNA修饰在AML的发生和发展中扮演着重要角色,尤其是RNA甲基化N^(6)-甲基腺嘌呤(m^(6)A)的异常调控得到了大量深入的研究。m^(6)A甲基化通过调节RNA代谢的多个方面,如RNA稳定性、翻译效率和剪接,参与调控白血病干细胞干性维持及自我更新。此外,RNA乙酰化修饰N^(4)-乙酰胞嘧啶(ac4C)也在AML代谢重编程及干性维持中发挥着关键作用。该综述以m^(6)A、5-甲基胞嘧啶(m^(5)C)、ac4C、假尿嘧啶(Ψ)和A-to-I RNA编辑为代表,详细总结了多种RNA修饰对基因表达调控的影响并深入探讨了其在AML疾病过程中的重要作用。此外,该文还讨论了目前靶向RNA修饰的小分子抑制剂的开发进展,提出了靶向RNA修饰作为AML新型治疗策略的良好前景。AML(acute myeloid leukemia)is a highly heterogeneous hematologic malignancy with a complex pathogenesis involving various epigenetic regulatory mechanisms.In recent years,emerging evidence shows that RNA modifications play a crucial role in the occurrence and development of AML.Particularly,the aberrance of m^(6)A(N^(6)-methyladenosine)in AML has been well and extensively studied.It has been revealed that m^(6)A methylation participates in regulating the maintenance of leukemic stem cell stemness and self-renewal by modulating RNA metabolism in many aspects,including stability,translation efficiency,and splicing.Besides,other RNA modifications,such as ac4C(N^(4)-acetylcytidine),also play key roles in metabolic reprogramming and stemness maintenance of AML cells.This review summarizes the effects of various RNA modifications on gene expression regulation and explores their significant roles in AML.Furthermore,this review compiles the current development and application of small molecule inhibitors targeting RNA modifications and discusses the promising prospects of targeting RNA modifications as a novel therapeutic strategy for AML.

关 键 词：急性髓系白血病 表观调控 RNA修饰 表观抑制剂 

分 类 号：R73[医药卫生—肿瘤]