Department of Laboratory Medicine, The Affiliated People's Hospital, Jiangsu University, Zhenjiang, China; Department of Immunology, Jiangsu Key Laboratory of Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, China.
Department of General Surgery, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu, China.
Biochim Biophys Acta Rev Cancer. 2021 Dec;1876(2):188609. doi: 10.1016/j.bbcan.2021.188609. Epub 2021 Aug 8.
N-methyladenosine (mA) is the most abundant and diverse epigenetic modification of mRNAs in eukaryotes, and it regulates biological metabolism, cell differentiation and cycles, and responses to heat shock stress, cancers and other diseases. RNA methyltransferase-like 3 (METTL3), methyltransferase-like 14 (METTL14) and other proteins possessing methyltransferase (MTase) capability including Wilms tumor 1-associated protein (WTAP), RNA-binding motif protein 15(RBM15), KIAA1429 and zinc finger CCCH-type containing 13 (ZC3H13) constitute the mA writer complex. Although METTL3 is the catalytic subunit, its activity is strongly dependent on METTL14, which is crucial in maintaining complex integrity and recognizing special RNA substrates. Currently, the roles of mA modification in cancers are being extensively reviewed. The critical functions of METTL14 in the occurrence and development of a variety of cancers as well as the potential targeting of METTL14 as a cancer treatment have not yet been highlighted. Therefore, in this review, we summarize the mA modification and focus on the structure and functions of METTL14 as well as its roles in oncogenesis, metastasis progression, treatment and prognosis in cancer.
N6-甲基腺苷（m6A）是真核生物中 mRNA 上最丰富、最多样化的表观遗传修饰之一，它调节生物代谢、细胞分化和周期以及对热休克应激、癌症和其他疾病的反应。RNA 甲基转移酶样 3（METTL3）、甲基转移酶样 14（METTL14）和其他具有甲基转移酶（MTase）能力的蛋白质，包括 Wilms 肿瘤 1 相关蛋白（WTAP）、RNA 结合基序蛋白 15（RBM15）、KIAA1429 和锌指 CCCH 型包含 13（ZC3H13），构成了 m6A 书写复合物。虽然 METTL3 是催化亚基，但它的活性强烈依赖于 METTL14，后者对于维持复合物的完整性和识别特殊的 RNA 底物至关重要。目前，m6A 修饰在癌症中的作用正在被广泛研究。METTL14 在多种癌症的发生和发展中的关键作用以及将 METTL14 作为癌症治疗的潜在靶点尚未得到强调。因此，在这篇综述中，我们总结了 m6A 修饰，并重点介绍了 METTL14 的结构和功能及其在肿瘤发生、转移进展、治疗和预后中的作用。
