Abstract
N6-methyladenosine (m6A) epitranscriptional modification has recently gained much attention. Through the development of m6A sequencing, the molecular mechanism and importance of m6A have been revealed. m6A is the most abundant internal modification in higher eukaryotic mRNAs, which plays crucial roles in mRNA metabolism and multiple biological processes. In this review, we introduce the characteristics of m6A regulators, including “writers” that create m6A mark, “erasers” that show demethylation activity and “readers” that decode m6A modification to govern the fate of modified transcripts. Moreover, we highlight the roles of m6A modification in several common cancers, including solid and non-solid tumors. The regulators of m6A exert enormous functions in cancer development, such as proliferation, migration and invasion. Especially, with the underlying mechanisms being uncovered, m6A and its regulators are expected to be the targets for the diagnosis and treatment of cancers.
Highlights
More than 100 kinds of chemical modifications of RNA have been identified in living organisms (Boccaletto et al, 2018)
A study has proved that methyltransferase-like 3 (METTL3) increases, methyltransferase-like 14 (METTL14) and alkB homolog 5 (ALKBH5) decrease, whereas FTO has no significant change in glioblastoma stem-like cells (GSCs)
Wilms’ tumor 1associating protein (WTAP) regulates the expression of certain genes related to motility of cancer cells, such as chemokine ligand 2 (CCL2), chemokine ligand 3 (CCL3), matrix metallopeptidase 3 (MMP3), lysyl oxidase-like 1 (LOXL1), hyaluronan synthase 1 (HAS1), m6A Modification and Cancers and thrombospondin 1 (THBS1) (Jin et al, 2012)
Summary
More than 100 kinds of chemical modifications of RNA have been identified in living organisms (Boccaletto et al, 2018). M6A modification regulates mRNA at different levels, including structure, maturation, stability, splicing, export, translation and decay (Liu and Zhang, 2018). METTL3 works on a chromatin-based pathway independently of METTL14 by localizing to the transcriptional start sites of active genes through CAATT-box binding protein (CEBPZ), which resulting in an increase of translation of the corresponding mRNA (Barbieri et al, 2017). A study has proved that METTL3 increases, METTL14 and ALKBH5 decrease, whereas FTO has no significant change in GSCs. METTL3 mediates GSCs maintenance and dedifferentiation by regulating the stability of the SOX2 mRNA though installing m6A on the SOX2-3′UTR. WTAP regulates the expression of certain genes related to motility of cancer cells, such as chemokine ligand 2 (CCL2), chemokine ligand 3 (CCL3), matrix metallopeptidase 3 (MMP3), lysyl oxidase-like 1 (LOXL1), hyaluronan synthase 1 (HAS1), FIGURE 2 | The roles of m6A regulatory proteins in AML. Certain evidence has confirmed that HuR, SOX2 and Nestin play a crucial role in this process (Zhang et al, 2017)
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