Hong Kwonho
Department of Stem Cell and Regenerative Biotechnology, Konkuk University, Gwangjin-gu, Seoul 05029, Republic of Korea.
Oncol Lett. 2018 Nov;16(5):5519-5524. doi: 10.3892/ol.2018.9395. Epub 2018 Sep 4.
N6-methyladenosine (m6A) modification in RNA has been implicated in diverse biological processes including the maintenance of embryonic stem cells, early development and diseases. Although the m6A modification was discovered several decades ago, its biological function remained unclear. The recent discovery of enzymes responsible for 'writing' or 'erasing' the modification and single-nucleotide resolution mapping by next-generation sequencing technology have revealed its function in biological processes. Its enrichment pattern is conserved in mammalian transcriptomes, and the level of m6A is tightly regulated by methyltransferases (writers), demethylases (erasers) and binding proteins (readers). Furthermore, accumulating evidence suggests that the aberrant regulation of m6A turnover is associated with multiple types of cancer including acute myeloid leukemia, breast cancer, glioblastoma, lung cancer and liver cancer. Studies have demonstrated that factors involved in m6A metabolism serve either oncogenic or tumor-suppressor roles in different contexts. The previous studies of the role of m6A in cancer biology are discussed in the present review.
RNA中的N6-甲基腺苷(m6A)修饰涉及多种生物学过程,包括胚胎干细胞的维持、早期发育和疾病。尽管m6A修饰在几十年前就已被发现,但其生物学功能仍不清楚。最近发现了负责“写入”或“擦除”该修饰的酶,以及通过下一代测序技术进行的单核苷酸分辨率图谱绘制,揭示了其在生物学过程中的功能。其富集模式在哺乳动物转录组中是保守的,m6A的水平受到甲基转移酶(写入器)、去甲基酶(擦除器)和结合蛋白(读取器)的严格调控。此外,越来越多的证据表明,m6A周转的异常调控与多种癌症有关,包括急性髓系白血病、乳腺癌、胶质母细胞瘤、肺癌和肝癌。研究表明,参与m6A代谢的因子在不同情况下发挥致癌或抑癌作用。本综述讨论了先前关于m6A在癌症生物学中作用的研究。