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      Link Between m6A Modification and Cancers

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          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.

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          Most cited references 22

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          Cytoplasmic m6A reader YTHDF3 promotes mRNA translation

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            Ythdc2 is an N6-methyladenosine binding protein that regulates mammalian spermatogenesis

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              Reversible RNA adenosine methylation in biological regulation.

              N(6)-methyladenosine (m(6)A) is a ubiquitous modification in mRNA and other RNAs across most eukaryotes. For many years, however, the exact functions of m(6)A were not clearly understood. The discovery that the fat mass and obesity-associated protein (FTO) is an m(6)A demethylase indicates that this modification is reversible and dynamically regulated, suggesting that it has regulatory roles. In addition, it has been shown that m(6)A affects cell fate decisions in yeast and plant development. Recent affinity-based m(6)A profiling in mouse and human cells further showed that this modification is a widespread mark in coding and noncoding RNA (ncRNA) transcripts and is likely dynamically regulated throughout developmental processes. Therefore, reversible RNA methylation, analogous to reversible DNA and histone modifications, may affect gene expression and cell fate decisions by modulating multiple RNA-related cellular pathways, which potentially provides rapid responses to various cellular and environmental signals, including energy and nutrient availability in mammals. Copyright © 2012 Elsevier Ltd. All rights reserved.
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                Author and article information

                Contributors
                Journal
                Front Bioeng Biotechnol
                Front Bioeng Biotechnol
                Front. Bioeng. Biotechnol.
                Frontiers in Bioengineering and Biotechnology
                Frontiers Media S.A.
                2296-4185
                13 July 2018
                2018
                : 6
                Affiliations
                1Center for Gene Diagnosis, Zhongnan Hospital of Wuhan University , Wuhan, China
                2Department of Chemistry and Institute for Biophysical Dynamics, Howard Hughes Medical Institute, University of Chicago , Chicago, IL, United States
                Author notes

                Edited by: Mario Acunzo, Virginia Commonwealth University, United States

                Reviewed by: Mattia Pelizzola, Fondazione Istituto Italiano di Technologia, Italy; Ioannis S. Vizirianakis, Aristotle University of Thessaloniki, Greece

                *Correspondence: Song-Mei Liu smliu@ 123456whu.edu.cn

                This article was submitted to Bioinformatics and Computational Biology, a section of the journal Frontiers in Bioengineering and Biotechnology

                †These authors have contributed equally to this work.

                Article
                10.3389/fbioe.2018.00089
                6055048
                Copyright © 2018 Liu, Li, Sun and Liu.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                Page count
                Figures: 4, Tables: 1, Equations: 0, References: 76, Pages: 11, Words: 7533
                Funding
                Funded by: National Natural Science Foundation of China 10.13039/501100001809
                Award ID: 81472023
                Award ID: 81772276
                Award ID: 91753201
                Categories
                Bioengineering and Biotechnology
                Review

                structures, function, cancers, mrna, m6a

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