Abstract
Abstract: Hepatocellular carcinoma (HCC) is the sixth globally diagnosed cancer with a poor prognosis. Although the pathological factors of hepatocellular carcinoma are well elucidated, the underlying molecular mechanisms remain unclear. N6-methyladenosine (M6A) is adenosine methylation occurring at the N6 site, which is the most prevalent modification of eukaryotic mRNA. Recent studies have shown that M6A can regulate gene expression, thus modulating the processes of cell self-renewal, differentiation, and apoptosis. The methyls in M6A are installed by methyltransferases (“writers”), removed by demethylases (“erasers”) and recognized by M6A-binding proteins (“readers”). In this review, we discuss the roles of the above regulators in the progression and prognosis of HCC, and summarize the clinical association between M6A modification and hepatocellular carcinoma, so as to provide more valuable information for clinical treatment.
Keywords: Hepatocellular carcinoma, N6-methyladenosine, RNA methylation, methyltransferase, demethylase, m6A-binding protein.
Graphical Abstract
[http://dx.doi.org/10.3322/caac.21387] [PMID: 28055103]
[http://dx.doi.org/10.2147/CMAR.S191565] [PMID: 31118805]
[http://dx.doi.org/10.2174/1574893614666191127101836]
[http://dx.doi.org/10.2174/1566523220666200628014530] [PMID: 32600231]
[http://dx.doi.org/10.1371/journal.pcbi.1008696] [PMID: 33561121]
[http://dx.doi.org/10.3389/fbioe.2020.00008] [PMID: 32047745]
[http://dx.doi.org/10.3389/fcell.2020.582864] [PMID: 33178697]
[http://dx.doi.org/10.3389/fbioe.2020.00254] [PMID: 32292778]
[http://dx.doi.org/10.1016/0022-2836(77)90047-X] [PMID: 196091]
[http://dx.doi.org/10.1128/jvi.20.1.45-53.1976] [PMID: 1086370]
[http://dx.doi.org/10.2174/1566523219666191023101433] [PMID: 31657677]
[http://dx.doi.org/10.1016/j.cell.2012.05.003] [PMID: 22608085]
[http://dx.doi.org/10.1038/nature11112] [PMID: 22575960]
[PMID: 9409616]
[http://dx.doi.org/10.1021/bi00627a023] [PMID: 856255]
[http://dx.doi.org/10.1016/j.cell.2017.05.045] [PMID: 28622506]
[http://dx.doi.org/10.1016/j.molcel.2016.05.041] [PMID: 27373337]
[http://dx.doi.org/10.1038/nature21073] [PMID: 28099411]
[http://dx.doi.org/10.1038/cr.2014.3] [PMID: 24407421]
[http://dx.doi.org/10.1038/nature19342] [PMID: 27602518]
[http://dx.doi.org/10.1016/j.molcel.2018.02.015] [PMID: 29547716]
[http://dx.doi.org/10.1111/nph.14586] [PMID: 28503769]
[http://dx.doi.org/10.1038/s41421-018-0019-0] [PMID: 29507755]
[http://dx.doi.org/10.1016/j.cell.2017.05.003] [PMID: 28525753]
[http://dx.doi.org/10.1038/nchembio.687] [PMID: 22002720]
[http://dx.doi.org/10.1016/j.molcel.2012.10.015] [PMID: 23177736]
[http://dx.doi.org/10.1016/j.febslet.2008.08.019] [PMID: 18775698]
[http://dx.doi.org/10.1039/C4SC02554G] [PMID: 28553460]
[http://dx.doi.org/10.1093/nar/gku085] [PMID: 24489119]
[http://dx.doi.org/10.1016/j.febslet.2014.02.021] [PMID: 24561204]
[http://dx.doi.org/10.1038/ncomms2822] [PMID: 23653210]
[http://dx.doi.org/10.1186/s12943-019-1033-z] [PMID: 31142332]
[http://dx.doi.org/10.1002/wrna.1547] [PMID: 31144457]
[http://dx.doi.org/10.1038/nchembio.1654] [PMID: 25242552]
[http://dx.doi.org/10.1016/j.cell.2015.05.014] [PMID: 26046440]
[http://dx.doi.org/10.1038/nature12730] [PMID: 24284625]
[http://dx.doi.org/10.1038/cr.2017.10] [PMID: 28106076]
[http://dx.doi.org/10.1038/cr.2017.15] [PMID: 28106072]
[http://dx.doi.org/10.1371/journal.pgen.1007412] [PMID: 29799838]
[http://dx.doi.org/10.1038/cr.2017.99] [PMID: 28809393]
[http://dx.doi.org/10.1186/s12943-019-1038-7] [PMID: 31230592]
[http://dx.doi.org/10.1093/nar/gky1012] [PMID: 30371874]
[http://dx.doi.org/10.1101/gad.325100.119] [PMID: 31221665]
[http://dx.doi.org/10.1016/j.cell.2015.08.011] [PMID: 26321680]
[http://dx.doi.org/10.1186/s13045-019-0839-x] [PMID: 31915027]
[http://dx.doi.org/10.1002/hep.29683] [PMID: 29171881]
[http://dx.doi.org/10.1038/s41467-019-09865-9] [PMID: 31061416]
[http://dx.doi.org/10.7150/thno.42539] [PMID: 32483411]
[http://dx.doi.org/10.1007/s13277-016-5215-7] [PMID: 27465557]
[http://dx.doi.org/10.1007/s11033-014-3817-y] [PMID: 25387436]
[http://dx.doi.org/10.1111/ecc.12464] [PMID: 26931363]
[http://dx.doi.org/10.1186/1471-2350-12-52] [PMID: 21489227]
[http://dx.doi.org/10.1111/cup.13575] [PMID: 31469442]
[http://dx.doi.org/10.3389/fgene.2019.01379] [PMID: 32038722]
[http://dx.doi.org/10.1073/pnas.1618520114] [PMID: 28137889]
[PMID: 31632576]
[http://dx.doi.org/10.3233/CBM-170791] [PMID: 29439311]
[http://dx.doi.org/10.1186/s12943-019-1106-z] [PMID: 31856849]
[http://dx.doi.org/10.2174/15680096113136660102] [PMID: 24168186]
[http://dx.doi.org/10.2147/OTT.S180954] [PMID: 31118692]
[http://dx.doi.org/10.1016/j.lfs.2020.118082] [PMID: 32653519]
[http://dx.doi.org/10.1038/s41388-020-1303-7] [PMID: 32366907]
[http://dx.doi.org/10.3389/fmolb.2020.604766] [PMID: 33363211]
[http://dx.doi.org/10.7150/thno.23012] [PMID: 29774077]
[http://dx.doi.org/10.1016/S0378-1119(01)00593-5] [PMID: 11595161]
[http://dx.doi.org/10.1016/j.ejca.2008.01.008] [PMID: 18255279]
[http://dx.doi.org/10.1186/s12943-019-1053-8] [PMID: 31438961]
[http://dx.doi.org/10.1038/cddis.2015.241] [PMID: 26426686]
[http://dx.doi.org/10.1136/gutjnl-2013-305736] [PMID: 24173291]
[http://dx.doi.org/10.1016/j.febslet.2015.06.038] [PMID: 26160756]
[http://dx.doi.org/10.3109/08977194.2016.1169532] [PMID: 27126374]
[http://dx.doi.org/10.1093/bioinformatics/btab036] [PMID: 33471060]
[http://dx.doi.org/10.1007/s10620-020-06260-z] [PMID: 32333311]
[http://dx.doi.org/10.18632/aging.101856] [PMID: 30877265]
[http://dx.doi.org/10.1016/j.cell.2018.10.006] [PMID: 30392959]
[http://dx.doi.org/10.1016/j.ccell.2017.02.013] [PMID: 28344040]
[http://dx.doi.org/10.1073/pnas.1602883113] [PMID: 27001847]
[http://dx.doi.org/10.1016/j.stem.2015.09.005] [PMID: 26526723]
[http://dx.doi.org/10.1186/s12943-020-01239-w] [PMID: 32772918]
[http://dx.doi.org/10.1016/j.canlet.2018.11.006] [PMID: 30423408]
[http://dx.doi.org/10.1002/hep.28885] [PMID: 27774652]
[PMID: 31934180]
[http://dx.doi.org/10.1186/s12943-019-1082-3] [PMID: 31735169]
[http://dx.doi.org/10.1002/cam4.2833] [PMID: 31943856]
[http://dx.doi.org/10.1186/s10020-020-00185-z] [PMID: 32552682]
[http://dx.doi.org/10.1155/2020/2053902] [PMID: 32733931]
[http://dx.doi.org/10.3389/fgene.2020.614566] [PMID: 33519919]
[http://dx.doi.org/10.1186/s12885-020-6638-5] [PMID: 32111180]
[http://dx.doi.org/10.3389/fmed.2020.00556] [PMID: 33072775]
[http://dx.doi.org/10.3389/fgene.2020.00863] [PMID: 32903675]
[http://dx.doi.org/10.3389/fonc.2020.00900] [PMID: 32850303]
[http://dx.doi.org/10.3892/ol.2020.11435] [PMID: 32256825]
[http://dx.doi.org/10.1016/j.neucom.2020.12.068]
[http://dx.doi.org/10.1038/s41575-019-0186-y] [PMID: 31439937]
[http://dx.doi.org/10.2174/1574893614666181119121916]
[http://dx.doi.org/10.1111/jcmm.13804] [PMID: 30039919]
[http://dx.doi.org/10.1186/s12943-018-0847-4] [PMID: 30031372]
[http://dx.doi.org/10.1093/bioinformatics/btx622] [PMID: 29028927]
[http://dx.doi.org/10.3390/ijms21145014] [PMID: 32708644]
[http://dx.doi.org/10.1093/nar/gky156] [PMID: 29506078]
[http://dx.doi.org/10.1136/gutjnl-2019-319639] [PMID: 31582403]
[http://dx.doi.org/10.1016/j.bbrc.2016.11.077] [PMID: 27856248]
[http://dx.doi.org/10.1093/nar/gkaa707] [PMID: 32833025]
[http://dx.doi.org/10.1093/nar/gkaa791] [PMID: 33010163]
[http://dx.doi.org/10.1093/nar/gku1173] [PMID: 25399422]
[http://dx.doi.org/10.1186/1471-2164-16-S3-S2] [PMID: 25707511]
[http://dx.doi.org/10.21037/hbsn.2019.10.16] [PMID: 31930004]