Abstract
N6-methyladenosine (m6A) modifications control multifaceted RNA metabolism and are one of the most extensively distributed modifications on the human transcriptome, including non-coding RNAs (ncRNAs). Previous concepts of ncRNAs as “junk” transcriptional products have evolved to the concept that ncRNAs are functional regulatory molecules that determine specific biological processes and cell fates. The dysregulation of m6A modifications and ncRNAs have been implicated in the development of human carcinogenesis. Certain types of ncRNAs have been reported to exert regulatory effects on m6A machinery. However, a better understanding of the relationship between m6A modifications and ncRNAs in cancer is still needed. This review discusses mutual interactions between m6A modifications and ncRNAs and their impacts on the development of human cancer. We summarize the clinical significance of m6A-ncRNA networks for cancer diagnosis and treatment, and we ask challenging questions that remain unanswered in this field of research. Understanding the complex coordination between m6A modifications and ncRNAs will be useful for guiding the development of therapeutic interventions.
Keywords: N6-methyladenosine, miRNA, LncRNA, CircRNA, PiRNA, non-coding RNA, cancer.
[http://dx.doi.org/10.1038/nmeth.3453] [PMID: 26121403]
[http://dx.doi.org/10.1038/nature11112] [PMID: 22575960]
[http://dx.doi.org/10.1146/annurev-cellbio-100616-060758] [PMID: 28759256]
[http://dx.doi.org/10.1038/cr.2014.3] [PMID: 24407421]
[http://dx.doi.org/10.1016/0300-9084(94)90038-8] [PMID: 7748945]
[PMID: 9409616]
[http://dx.doi.org/10.1038/ncb2902] [PMID: 24394384]
[http://dx.doi.org/10.1038/nchembio.1432] [PMID: 24316715]
[http://dx.doi.org/10.1038/nature19342] [PMID: 27602518]
[http://dx.doi.org/10.1101/gad.309146.117] [PMID: 29535189]
[http://dx.doi.org/10.1038/s41421-018-0019-0] [PMID: 29507755]
[http://dx.doi.org/10.1093/nar/gkz1206] [PMID: 31912146]
[http://dx.doi.org/10.1038/nature18298] [PMID: 27281194]
[http://dx.doi.org/10.1016/j.molcel.2016.05.041] [PMID: 27373337]
[http://dx.doi.org/10.7554/eLife.18434] [PMID: 27627798]
[http://dx.doi.org/10.15252/embr.201744940] [PMID: 29051200]
[http://dx.doi.org/10.1038/s41589-018-0184-3] [PMID: 30531910]
[http://dx.doi.org/10.1093/nar/gkz619] [PMID: 31328227]
[http://dx.doi.org/10.1038/nchembio.687] [PMID: 22002720]
[http://dx.doi.org/10.1007/s11684-018-0654-8] [PMID: 30097961]
[http://dx.doi.org/10.1016/j.omtn.2019.11.022] [PMID: 31887551]
[http://dx.doi.org/10.1038/s41422-018-0113-8] [PMID: 30514900]
[http://dx.doi.org/10.1080/15548627.2019.1586246] [PMID: 30870073]
[http://dx.doi.org/10.1038/s41586-019-1016-7] [PMID: 30867593]
[http://dx.doi.org/10.1016/j.celrep.2018.05.077] [PMID: 29924987]
[http://dx.doi.org/10.1038/nature25784] [PMID: 29489750]
[http://dx.doi.org/10.1038/nature24678] [PMID: 29186125]
[http://dx.doi.org/10.1016/j.celrep.2017.02.059] [PMID: 28297667]
[http://dx.doi.org/10.1016/j.molcel.2016.03.021] [PMID: 27117702]
[http://dx.doi.org/10.1002/hep.29683] [PMID: 29171881]
[http://dx.doi.org/10.1186/s12943-019-1088-x] [PMID: 31722709]
[http://dx.doi.org/10.1093/nar/gkaa048] [PMID: 31996915]
[http://dx.doi.org/10.1016/j.ccell.2016.11.017] [PMID: 28017614]
[http://dx.doi.org/10.1002/mc.22782] [PMID: 29315835]
[http://dx.doi.org/10.1126/science.1098119] [PMID: 15131266]
[http://dx.doi.org/10.1016/j.bbagen.2013.10.035] [PMID: 24184936]
[http://dx.doi.org/10.1038/nature11233] [PMID: 22955620]
[http://dx.doi.org/10.1186/s12943-020-01171-z] [PMID: 32122355]
[http://dx.doi.org/10.1038/nrg2843] [PMID: 20661255]
[http://dx.doi.org/10.1016/j.stem.2015.01.016] [PMID: 25683224]
[http://dx.doi.org/10.1038/nature14281] [PMID: 25799998]
[http://dx.doi.org/10.1038/s41598-019-45636-8] [PMID: 31263129]
[http://dx.doi.org/10.1016/j.bbrc.2016.11.077] [PMID: 27856248]
[http://dx.doi.org/10.1074/jbc.M116.749689] [PMID: 28104805]
[http://dx.doi.org/10.1038/s41467-019-09712-x] [PMID: 31015415]
[http://dx.doi.org/10.1186/s12943-019-1036-9] [PMID: 31228940]
[http://dx.doi.org/10.1016/j.prp.2019.152666] [PMID: 31606241]
[http://dx.doi.org/10.1002/hep.28885] [PMID: 27774652]
[http://dx.doi.org/10.1016/j.molcel.2019.06.001]
[http://dx.doi.org/10.1038/nrg2521] [PMID: 19188922]
[http://dx.doi.org/10.1146/annurev.neuro.29.051605.112839] [PMID: 16776580]
[http://dx.doi.org/10.1186/s12943-019-1014-2] [PMID: 30979372]
[http://dx.doi.org/10.1158/0008-5472.CAN-19-0799] [PMID: 31331909]
[PMID: 31497208]
[http://dx.doi.org/10.1038/s41419-019-1585-2] [PMID: 31097692]
[http://dx.doi.org/10.1038/nbt.2890] [PMID: 24811520]
[http://dx.doi.org/10.1080/15476286.2016.1220473] [PMID: 27617908]
[http://dx.doi.org/10.1002/wrna.1386] [PMID: 27612318]
[http://dx.doi.org/10.1186/s12943-019-1121-0] [PMID: 32061256]
[http://dx.doi.org/10.1038/cr.2017.31] [PMID: 28281539]
[http://dx.doi.org/10.1038/s41467-019-12651-2] [PMID: 31619685]
[http://dx.doi.org/10.1038/s41467-019-10246-5] [PMID: 31127091]
[http://dx.doi.org/10.1016/j.molcel.2019.07.016]
[http://dx.doi.org/10.1038/s41419-018-1132-6] [PMID: 30361504]
[http://dx.doi.org/10.1038/nature23482] [PMID: 28847004]
[http://dx.doi.org/10.1186/s12943-019-1052-9] [PMID: 31399034]
[http://dx.doi.org/10.1182/blood-2018-99-114292]
[http://dx.doi.org/10.1126/science.aay6018] [PMID: 31949099]
[http://dx.doi.org/10.1038/s41586-019-0916-x] [PMID: 30728504]
[PMID: 29345285]
[http://dx.doi.org/10.1021/ja3064149] [PMID: 23045983]
[http://dx.doi.org/10.1021/acs.jmedchem.5b00702] [PMID: 26314339]
[http://dx.doi.org/10.1021/acs.biochem.6b00023] [PMID: 26915401]
[http://dx.doi.org/10.1093/nar/gku1276] [PMID: 25452335]
[http://dx.doi.org/10.1146/annurev.ge.29.120195.000441] [PMID: 8825469]
[http://dx.doi.org/10.1146/annurev-biochem-061516-044724] [PMID: 29494239]
[http://dx.doi.org/10.1016/j.bbrc.2019.07.058] [PMID: 31395342]
[http://dx.doi.org/10.1111/cpr.12768] [PMID: 31967701]
[http://dx.doi.org/10.1186/s12943-019-1079-y] [PMID: 31619268]
[http://dx.doi.org/10.1186/s13046-019-1408-4] [PMID: 31492150]
[http://dx.doi.org/10.1038/s41467-019-11826-1] [PMID: 31467274]
[http://dx.doi.org/10.1159/000491915] [PMID: 30032148]