Volume 3,Issue 9
METTL3调控致癌发生的机制及其抑制剂研发进展
N6-甲基腺嘌呤（m6A）是真核生物信使RNA（mRNA）中最普遍的一种内部化学修饰。该修饰过程由三类功能蛋白共同调控：甲基转移酶（writer）、去甲基化酶（eraser）和甲基化阅读蛋白（reader）。其中，甲基转移酶样蛋白3（METTL3）是催化m6A形成的关键酶，也是m6A甲基转移酶复合体的核心催化亚基。METTL3在多种恶性肿瘤中异常高表达，通过调控致癌信号通路成为潜在的抗癌新靶点。本综述主要阐述了METTL3通过m6A依赖性机制和非m6A依赖性机制（如PI3K/AKT/mTOR、JAK/STAT等信号通路关键基因的翻译与稳定性）来促进癌细胞的存活、增殖和侵袭，从而发挥致癌作用，以及总结了目前关于靶向METTL3的小分子抑制剂和蛋白降解剂的最新研发进展与抗肿瘤效果。最后，本文分析了靶向METTL3在临床转化中所面临的关键挑战，并展望了其未来发展方向，旨在为基于表观转录组调控的新型药物研发提供理论参考。
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