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      Function of N6-Methyladenosine Modification in Tumors

      review-article
      , , ,
      Journal of Oncology
      Hindawi

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          Abstract

          N6-Methyladenosine (m6A) modification is a dynamic and reversible methylation modification at the N6-position of adenosine. As one of the most prevalent posttranscriptional methylation modifications of RNA, m6A modification participates in several mRNA processes, including nuclear export, splicing, translation, and degradation. Some proteins, such as METTL3, METTL14, WTAP, ALKBH5, FTO, and YTHDF1/2/3, are involved in methylation. These proteins are subdivided into writers (METTL3, METTL14, WTAP), erasers (ALKBH5, FTO), and readers (YTHDF1/2/3) according to their functions in m6A modification. Several studies have shown that abnormal m6A modification occurs in tumors, including colorectal cancer, liver cancer, breast cancer, nasopharyngeal carcinoma, and gastric cancer. The proteins for m6A modification are involved in tumor proliferation, angiogenesis, metastasis, immunity, and other processes. Herein, the roles of m6A modification in cancer are discussed, which will improve the understanding of tumorigenesis, as well as the diagnosis, treatment, and prognosis of tumors.

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          Most cited references93

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          Molecular mechanisms of epithelial-mesenchymal transition.

          The transdifferentiation of epithelial cells into motile mesenchymal cells, a process known as epithelial-mesenchymal transition (EMT), is integral in development, wound healing and stem cell behaviour, and contributes pathologically to fibrosis and cancer progression. This switch in cell differentiation and behaviour is mediated by key transcription factors, including SNAIL, zinc-finger E-box-binding (ZEB) and basic helix-loop-helix transcription factors, the functions of which are finely regulated at the transcriptional, translational and post-translational levels. The reprogramming of gene expression during EMT, as well as non-transcriptional changes, are initiated and controlled by signalling pathways that respond to extracellular cues. Among these, transforming growth factor-β (TGFβ) family signalling has a predominant role; however, the convergence of signalling pathways is essential for EMT.
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            Topology of the human and mouse m6A RNA methylomes revealed by m6A-seq.

            An extensive repertoire of modifications is known to underlie the versatile coding, structural and catalytic functions of RNA, but it remains largely uncharted territory. Although biochemical studies indicate that N(6)-methyladenosine (m(6)A) is the most prevalent internal modification in messenger RNA, an in-depth study of its distribution and functions has been impeded by a lack of robust analytical methods. Here we present the human and mouse m(6)A modification landscape in a transcriptome-wide manner, using a novel approach, m(6)A-seq, based on antibody-mediated capture and massively parallel sequencing. We identify over 12,000 m(6)A sites characterized by a typical consensus in the transcripts of more than 7,000 human genes. Sites preferentially appear in two distinct landmarks--around stop codons and within long internal exons--and are highly conserved between human and mouse. Although most sites are well preserved across normal and cancerous tissues and in response to various stimuli, a subset of stimulus-dependent, dynamically modulated sites is identified. Silencing the m(6)A methyltransferase significantly affects gene expression and alternative splicing patterns, resulting in modulation of the p53 (also known as TP53) signalling pathway and apoptosis. Our findings therefore suggest that RNA decoration by m(6)A has a fundamental role in regulation of gene expression.
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              A METTL3-METTL14 complex mediates mammalian nuclear RNA N6-adenosine methylation

              N 6-methyladenosine (m6A) is the most prevalent and reversible internal modification in mammalian messenger and non-coding RNAs. We report here that human METTL14 catalyzes m6A RNA methylation. Together with METTL3, the only previously known m6A methyltransferase, these two proteins form a stable heterodimer core complex of METTL3-14 that functions in cellular m6A deposition on mammalian nuclear RNAs. WTAP, a mammalian splicing factor, can interact with this complex and affect this methylation.
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                Author and article information

                Contributors
                Journal
                J Oncol
                J Oncol
                jo
                Journal of Oncology
                Hindawi
                1687-8450
                1687-8469
                2021
                23 November 2021
                : 2021
                : 6461552
                Affiliations
                Department of Physiology, Institute of Neuroscience Research, Hengyang Key Laboratory of Neurodegeneration and Cognitive Impairment, Hengyang Medical School, University of South China, 28 West Changsheng Road, Hengyang 421001, Hunan, China
                Author notes

                Academic Editor: Alessandro Granito

                Author information
                https://orcid.org/0000-0001-9131-3755
                Article
                10.1155/2021/6461552
                8632389
                34858499
                7da4aa95-6920-473e-8be2-fe0f4b26f962
                Copyright © 2021 Nan Zhang et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 10 October 2021
                : 30 October 2021
                : 1 November 2021
                Funding
                Funded by: National Natural Science Foundation of China
                Award ID: 81903030
                Funded by: Education Department of Hunan Province
                Award ID: 18B274
                Funded by: Natural Science Foundation of Hunan Province
                Award ID: 2021JJ40481
                Funded by: University of South China
                Award ID: S202110555298
                Categories
                Review Article

                Oncology & Radiotherapy
                Oncology & Radiotherapy

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