Emerging function of N6‑methyladenosine in cancer (Review)

Abstract

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. Contents 1. Introduction 2. m6A enrichment and its function 3. Factors metabolizing m6A 4. Role of m6A in cancer 5. Perspectives

METTL3 Attenuates LPS-Induced Inflammatory Response in Macrophages via NF-κB Signaling Pathway

“…The NF-κB signaling pathway is a classic pathway related to inflammation and immune regulation in RA [37]. Growing data showed that expression and regulation of m 6 A methylation-related genes are associated with a variety of immune signaling pathways, particularly the NF-κB pathway [8,18]. In this study, METTL3 has been found to be upregulated in peripheral blood monocytes, the critical cell type in PMBCs involved in inflammation and immune regulations.…”

“…During the past few years, the role of N 6 -methyladenosine (m 6 A) methylation of RNA in autoimmunity, inflammation, and cancer has drawn close attention [7][8][9][10]. m 6 A is the most common posttranscription modification of RNA [11].…”

Comprehensive in vivo identification of the c-Myc mRNA protein interactome using HyPR-MS

“…YTHDF2, a N6-methyladenosine (m6A) "reader" protein, is a confirmed binder of c-Myc mRNA and is involved in increasing stability and expression of c-Myc in K562 cells, the same cells used in this study (Su et al 2018). The m6A modification can be added to nascent transcripts during maturation events (Ke et al 2017) and correlates with enhanced c-Myc mRNA translation (Hong 2018). RPL11 is involved in the regulation of c-Myc mRNA stability and promotes degradation by binding to the 3 ′ -UTR and recruiting the RNAinduced silencing complex (miR-24/RISC complex) to the c-Myc transcript in response to ribosomal stress (Challagundla et al 2011).…”

Landscape and regulation of m6A and m6Am methylome across human and mouse tissues

“…Moreover, m 6 A-dependent mRNA regulation has now been demonstrated to regulate the process of circadian rhythm, adipogenesis, spermatogenesis, embryonic stem cell self-renewal and differentiation (Fu et al, 2014). The aberrant regulation of m 6 A is related to a variety of cancers including acute myeloid leukemia, breast cancer, glioblastoma, lung cancer and liver cancer (Hong, 2018; Luo et al, 2018), which highlight the important regulatory roles of m 6 A.…”