Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, 450052, P.R. China.
Zhejiang Cancer Institute, Zhejiang Cancer Hospital, No.1 Banshan East Rd., Gongshu District, Hangzhou, 310022, Zhejiang, P.R. China.
J Hematol Oncol. 2023 Aug 2;16(1):89. doi: 10.1186/s13045-023-01477-7.
RNA modification has recently become a significant process of gene regulation, and the methyltransferase-like (METTL) family of proteins plays a critical role in RNA modification, methylating various types of RNAs, including mRNA, tRNA, microRNA, rRNA, and mitochondrial RNAs. METTL proteins consist of a unique seven-beta-strand domain, which binds to the methyl donor SAM to catalyze methyl transfer. The most typical family member METTL3/METTL14 forms a methyltransferase complex involved in N6-methyladenosine (m6A) modification of RNA, regulating tumor proliferation, metastasis and invasion, immunotherapy resistance, and metabolic reprogramming of tumor cells. METTL1, METTL4, METTL5, and METTL16 have also been recently identified to have some regulatory ability in tumorigenesis, and the rest of the METTL family members rely on their methyltransferase activity for methylation of different nucleotides, proteins, and small molecules, which regulate translation and affect processes such as cell differentiation and development. Herein, we summarize the literature on METTLs in the last three years to elucidate their roles in human cancers and provide a theoretical basis for their future use as potential therapeutic targets.
RNA 修饰最近成为基因调控的重要过程，甲基转移酶样（METTL）家族蛋白在 RNA 修饰中发挥着关键作用，可甲基化各种类型的 RNA，包括 mRNA、tRNA、miRNA、rRNA 和线粒体 RNA。METTL 蛋白由独特的七-β链结构域组成，该结构域与甲基供体 SAM 结合，催化甲基转移。最典型的家族成员 METTL3/METTL14 形成参与 RNA N6-甲基腺苷（m6A）修饰的甲基转移酶复合物，调节肿瘤增殖、转移和侵袭、免疫治疗抵抗以及肿瘤细胞的代谢重编程。METTL1、METTL4、METTL5 和 METTL16 最近也被确定在肿瘤发生中有一定的调节能力，其余的 METTL 家族成员依赖其甲基转移酶活性对不同的核苷酸、蛋白质和小分子进行甲基化，调节翻译并影响细胞分化和发育等过程。在此，我们总结了过去三年中关于 METTL 的文献，以阐明它们在人类癌症中的作用，并为它们未来作为潜在治疗靶点的应用提供理论依据。
