Emerging function of N6‑methyladenosine in cancer (Review)
- Authors:
- Kwonho Hong
-
Affiliations: Department of Stem Cell and Regenerative Biotechnology, Konkuk University, Gwangjin‑gu, Seoul 05029, Republic of Korea - Published online on: September 4, 2018 https://doi.org/10.3892/ol.2018.9395
- Pages: 5519-5524
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Machnicka MA, Milanowska K, Oglou Osman O, Purta E, Kurkowska M, Olchowik A, Januszewski W, Kalinowski S, Dunin-Horkawicz S, Rother KM, et al: MODOMICS: A database of RNA modification pathways-2013 update. Nucleic Acids Res. 41:(Database Issue). D262–D267. 2013. View Article : Google Scholar : PubMed/NCBI | |
|
Batista PJ, Molinie B, Wang J, Qu K, Zhang J, Li L, Bouley DM, Lujan E, Haddad B, Daneshvar K, et al: m(6)A RNA modification controls cell fate transition in mammalian embryonic stem cells. Cell Stem Cell. 15:707–719. 2014. View Article : Google Scholar : PubMed/NCBI | |
|
Geula S, Moshkovitz Moshitch S, Dominissini D, Mansour AA, Kol N, Divon Salmon M, Hershkovitz V, Peer E, Mor N, Manor YS, et al: Stem cells. m6A mRNA methylation facilitates resolution of naïve pluripotency toward differentiation. Science. 347:1002–1006. 2015. View Article : Google Scholar : PubMed/NCBI | |
|
O'Connell MA, Mannion NM and Keegan LP: The epitranscriptome and innate immunity. PLoS Genet. 11:e10056872015. View Article : Google Scholar : PubMed/NCBI | |
|
Tajaddod M, Jantsch MF and Licht K: The dynamic epitranscriptome: A to I editing modulates genetic information. Chromosoma. 125:51–63. 2016. View Article : Google Scholar : PubMed/NCBI | |
|
Desrosiers R, Friderici K and Rottman F: Identification of methylated nucleosides in messenger RNA from novikoff hepatoma cells. Proc Natl Acad Sci USA. 71:3971–3975. 1974. View Article : Google Scholar : PubMed/NCBI | |
|
Perry RP and Kelley DE: Existence of methylated messenger RNA in mouse L cells. Cell. 1:37–42. 1974. View Article : Google Scholar | |
|
Adams JM and Cory S: Modified nucleosides and bizarre 5′-termini in mouse myeloma mRNA. Nature. 255:28–33. 1975. View Article : Google Scholar : PubMed/NCBI | |
|
Furuichi Y, Shatkin AJ, Stavnezer E and Bishop JM: Blocked, methylated 5′-terminal sequence in avian sarcoma virus RNA. Nature. 257:618–620. 1975. View Article : Google Scholar : PubMed/NCBI | |
|
Lavi S and Shatkin AJ: Methylated simian virus 40-specific RNA from nuclei and cytoplasm of infected BSC-1 cells. Proc Natl Acad Sci USA. 72:2012–2016. 1975. View Article : Google Scholar : PubMed/NCBI | |
|
Wei CM, Gershowitz A and Moss B: Methylated nucleotides block 5′ terminus of HeLa cell messenger RNA. Cell. 4:379–386. 1975. View Article : Google Scholar : PubMed/NCBI | |
|
Jia G, Fu Y, Zhao X, Dai Q, Zheng G, Yang Y, Yi C, Lindahl T, Pan T, Yang YG and He C: N6-methyladenosine in nuclear RNA is a major substrate of the obesity-associated FTO. Nat Chem Biol. 7:885–887. 2011. View Article : Google Scholar : PubMed/NCBI | |
|
Scuteri A, Sanna S, Chen WM, Uda M, Albai G, Strait J, Najjar SS, Nagarajah R, Orrú M, Usala G, et al: Genome-wide association scan shows genetic variants in the FTO gene are associated with obesity related traits. PLoS Genet. 3:e1152007. View Article : Google Scholar : PubMed/NCBI | |
|
Dina C, Meyre D, Gallina S, Durand E, Körner A, Jacobson P, Carlsson LM, Kiess W, Vatin V, Lecoeur C, et al: Variation in FTO contributes to childhood obesity and severe adult obesity. Nat Genet. 39:724–726. 2007. View Article : Google Scholar : PubMed/NCBI | |
|
Frayling TM, Timpson NJ, Weedon MN, Zeggini E, Freathy RM, Lindgren CM, Perry JR, Elliott KS, Lango H, Rayner NW, et al: A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity. Science. 316:889–894. 2007. View Article : Google Scholar : PubMed/NCBI | |
|
Dominissini D, Moshkovitz Moshitch S, Schwartz S, Divon Salmon M, Ungar L, Osenberg S, Cesarkas K, Hirsch Jacob J, Amariglio N, Kupiec M, et al: Topology of the human and mouse m6A RNA methylomes revealed by m6A-seq. Nature. 485:201–206. 2012. View Article : Google Scholar : PubMed/NCBI | |
|
Meyer KD, Saletore Y, Zumbo P, Elemento O, Mason CE and Jaffrey SR: Comprehensive analysis of mRNA methylation reveals enrichment in 3′ UTRs and near stop codons. Cell. 149:1635–1646. 2012. View Article : Google Scholar : PubMed/NCBI | |
|
Shen F, Huang W, Huang JT, Xiong J, Yang Y, Wu K, Jia GF, Chen J, Feng YQ, Yuan BF and Liu SM: Decreased N(6)-methyladenosine in peripheral blood RNA from diabetic patients is associated with FTO expression rather than ALKBH5. J Clin Endocrinol Metab. 100:E148–E154. 2015. View Article : Google Scholar : PubMed/NCBI | |
|
Yang Y, Huang W, Huang JT, Shen F, Xiong J, Yuan EF, Qin SS, Zhang M, Feng YQ, Yuan BF and Liu SM: Increased N6-methyladenosine in human sperm RNA as a risk factor for asthenozoospermia. Sci Rep. 6:243452016. View Article : Google Scholar : PubMed/NCBI | |
|
Fustin JM, Doi M, Yamaguchi Y, Hida H, Nishimura S, Yoshida M, Isagawa T, Morioka MS, Kakeya H, Manabe I and Okamura H: RNA-methylation-dependent RNA processing controls the speed of the circadian clock. Cell. 155:793–806. 2013. View Article : Google Scholar : PubMed/NCBI | |
|
Daoud H, Zhang D, Mcmurray F, Yu A, Luco SM, Vanstone J, Jarinova O, Carson N, Wickens J, Shishodia S, et al: Identification of a pathogenic FTO mutation by next-generation sequencing in a newborn with growth retardation and developmental delay. J Med Genet. 53:200–207. 2016. View Article : Google Scholar : PubMed/NCBI | |
|
Davis W, van Rensburg SJ, Cronje FJ, Whati L, Fisher LR, van der Merwe L, Geiger D, Hassan MS, Matsha T, Erasmus RT and Kotze MJ: The fat mass and obesity-associated FTO rs9939609 polymorphism is associated with elevated homocysteine levels in patients with multiple sclerosis screened for vascular risk factors. Metab Brain Dis. 29:409–419. 2014.PubMed/NCBI | |
|
Zhang C, Samanta D, Lu H, Bullen JW, Zhang H, Chen I, He X and Semenza GL: Hypoxia induces the breast cancer stem cell phenotype by HIF-dependent and ALKBH5-mediated m6A-demethylation of NANOG mRNA. Proc Natl Acad Sci USA. 113:E2047–E2056. 2016. View Article : Google Scholar : PubMed/NCBI | |
|
Zhang C, Zhi WI, Lu H, Samanta D, Chen I, Gabrielson E and Semenza GL: Hypoxia-inducible factors regulate pluripotency factor expression by ZNF217- and ALKBH5-mediated modulation of RNA methylation in breast cancer cells. Oncotarget. 7:64527–64542. 2016.PubMed/NCBI | |
|
Bansal H, Yihua Q, Iyer SP, Ganapathy S, Proia DA, Penalva LO, Uren PJ, Suresh U, Carew JS, Karnad AB, et al: WTAP is a novel oncogenic protein in acute myeloid leukemia. Leukemia. 28:1171–1174. 2014. View Article : Google Scholar : PubMed/NCBI | |
|
Kwok CT, Marshall AD, Rasko JE and Wong JJ: Genetic alterations of m6A regulators predict poorer survival in acute myeloid leukemia. J Hematol Oncol. 10:392017. View Article : Google Scholar : PubMed/NCBI | |
|
Zhang C, Chen Y, Sun B, Wang L, Yang Y, Ma D, Lv J, Heng J, Ding Y, Xue Y, et al: m6A modulates haematopoietic stem and progenitor cell specification. Nature. 549:273–276. 2017. View Article : Google Scholar : PubMed/NCBI | |
|
Barbieri I, Tzelepis K, Pandolfini L, Shi J, Millán-Zambrano G, Robson SC, Aspris D, Migliori V, Bannister AJ, Han N, et al: Promoter-bound METTL3 maintains myeloid leukaemia by m6A-dependent translation control. Nature. 552:126–131. 2017.PubMed/NCBI | |
|
Vu LP, Pickering BF, Cheng Y, Zaccara S, Nguyen D, Minuesa G, Chou T, Chow A, Saletore Y, MacKay M, et al: The N6-methyladenosine (m6A)-forming enzyme METTL3 controls myeloid differentiation of normal hematopoietic and leukemia cells. Nat Med. 23:1369–1376. 2017.PubMed/NCBI | |
|
Li Z, Weng H, Su R, Weng X, Zuo Z, Li C, Huang H, Nachtergaele S, Dong L, Hu C, et al: FTO plays an oncogenic role in acute myeloid leukemia as a N6-methyladenosine RNA demethylase. Cancer Cell. 31:127–141. 2017. View Article : Google Scholar : PubMed/NCBI | |
|
Zhang S, Zhao BS, Zhou A, Lin K, Zheng S, Lu Z, Chen Y, Sulman EP, Xie K, Bögler O, et al: m6A demethylase ALKBH5 maintains tumorigenicity of glioblastoma stem-like cells by sustaining FOXM1 expression and cell proliferation program. Cancer Cell. 31(591–606): e62017. View Article : Google Scholar | |
|
Cui Q, Shi H, Ye P, Li L, Qu Q, Sun G, Sun G, Lu Z, Huang Y, Yang CG, et al: m6A RNA methylation regulates the self-renewal and tumorigenesis of glioblastoma stem cells. Cell Rep. 18:2622–2634. 2017. View Article : Google Scholar : PubMed/NCBI | |
|
Jin DI, Lee SW, Han ME, Kim HJ, Seo SA, Hur GY, Jung S, Kim BS and Oh SO: Expression and roles of Wilms' tumor 1-associating protein in glioblastoma. Cancer Sci. 103:2102–2109. 2012. View Article : Google Scholar : PubMed/NCBI | |
|
Lin S, Choe J, Du P, Triboulet R and Gregory RI: The m(6)A methyltransferase METTL3 promotes translation in human cancer cells. Mol Cell. 62:335–345. 2016. View Article : Google Scholar : PubMed/NCBI | |
|
Chen M, Wei L, Law CT, Tsang FH, Shen J, Cheng CL, Tsang LH, Ho DW, Chiu DK, Lee JM, et al: RNA N6-methyladenosine methyltransferase-like 3 promotes liver cancer progression through YTHDF2 dependent posttranscriptional silencing of SOCS2. Hepatology. 67:2254–2270. 2018. View Article : Google Scholar : PubMed/NCBI | |
|
Horowitz S, Horowitz A, Nilsen TW, Munns TW and Rottman FM: Mapping of N6-methyladenosine residues in bovine prolactin mRNA. Proc Natl Acad Sci USA. 81:5667–5671. 1984. View Article : Google Scholar : PubMed/NCBI | |
|
Schwartz S, Agarwala SD, Mumbach MR, Jovanovic M, Mertins P, Shishkin A, Tabach Y, Mikkelsen TS, Satija R, Ruvkun G, et al: High-resolution mapping reveals a conserved, widespread, dynamic mRNA methylation program in yeast meiosis. Cell. 155:1409–1421. 2013. View Article : Google Scholar : PubMed/NCBI | |
|
Luo GZ, MacQueen A, Zheng G, Duan H, Dore LC, Lu Z, Liu J, Chen K, Jia G, Bergelson J and He C: Unique features of the m6A methylome in Arabidopsis thaliana. Nat Commun. 5:56302014. View Article : Google Scholar : PubMed/NCBI | |
|
Zhao X, Yang Y, Sun BF, Shi Y, Yang X, Xiao W, Hao YJ, Ping XL, Chen YS, Wang WJ, et al: FTO-dependent demethylation of N6-methyladenosine regulates mRNA splicing and is required for adipogenesis. Cell Res. 24:1403–1419. 2014. View Article : Google Scholar : PubMed/NCBI | |
|
Ping XL, Sun BF, Wang L, Xiao W, Yang X, Wang WJ, Adhikari S, Shi Y, Lv Y, Chen YS, et al: Mammalian WTAP is a regulatory subunit of the RNA N6-methyladenosine methyltransferase. Cell Res. 24:177–189. 2014. View Article : Google Scholar : PubMed/NCBI | |
|
Smemo S, Tena JJ, Kim KH, Gamazon ER, Sakabe NJ, Gómez-Marín C, Aneas I, Credidio FL, Sobreira DR, Wasserman NF, et al: Obesity-associated variants within FTO form long range functional connections with IRX3. Nature. 507:371–375. 2014. View Article : Google Scholar : PubMed/NCBI | |
|
Rottman F, Shatkin AJ and Perry RP: Sequences containing methylated nucleotides at the 5′ termini of messenger RNAs: Possible implications for processing. Cell. 3:197–199. 1974. View Article : Google Scholar : PubMed/NCBI | |
|
Mauer J, Luo X, Blanjoie A, Jiao X, Grozhik AV, Patil DP, Linder B, Pickering BF, Vasseur JJ, Chen Q, et al: Reversible methylation of m6Am in the 5′ cap controls mRNA stability. Nature. 541:371–375. 2017. View Article : Google Scholar : PubMed/NCBI | |
|
Wang Y, Li Y, Toth JI, Petroski MD, Zhang Z and Zhao JC: N6-methyladenosine modification destabilizes developmental regulators in embryonic stem cells. Nat Cell Biol. 16:191–198. 2014. View Article : Google Scholar : PubMed/NCBI | |
|
Wang X, Lu Z, Gomez A, Hon GC, Yue Y, Han D, Fu Y, Parisien M, Dai Q, Jia G, et al: N6-methyladenosine-dependent regulation of messenger RNA stability. Nature. 505:117–120. 2014. View Article : Google Scholar : PubMed/NCBI | |
|
Yang Y, Sun BF, Xiao W, Yang X, Sun HY, Zhao YL and Yang YG: Dynamic m6A modification and its emerging regulatory role in mRNA splicing. Sci Bull. 60:21–32. 2015. View Article : Google Scholar | |
|
Meyer KD, Patil DP, Zhou J, Zinoviev A, Skabkin MA, Elemento O, Pestova TV, Qian SB and Jaffrey SR: 5′ UTR m(6)A promotes cap-independent translation. Cell. 163:999–1010. 2015. View Article : Google Scholar : PubMed/NCBI | |
|
Ke S, Pandya-Jones A, Saito Y, Fak JJ, Vågbø CB, Geula S, Hanna JH, Black DL, Darnell JE Jr and Darnell RB: m6A mRNA modifications are deposited in nascent pre-mRNA and are not required for splicing but do specify cytoplasmic turnover. Genes Dev. 31:990–1006. 2017. View Article : Google Scholar : PubMed/NCBI | |
|
Ke S, Alemu EA, Mertens C, Gantman EC, Fak JJ, Mele A, Haripal B, Zucker-Scharff I, Moore MJ, Park CY, et al: A majority of m6A residues are in the last exons, allowing the potential for 3′ UTR regulation. Genes Dev. 29:2037–2053. 2015. View Article : Google Scholar : PubMed/NCBI | |
|
Bokar JA, Shambaugh ME, Polayes D, Matera AG and Rottman FM: Purification and cDNA cloning of the AdoMet-binding subunit of the human mRNA (N6-adenosine)-methyltransferase. RNA. 3:1233–1247. 1997.PubMed/NCBI | |
|
Liu J, Yue Y, Han D, Wang X, Fu Y, Zhang L, Jia G, Yu M, Lu Z, Deng X, et al: A METTL3-METTL14 complex mediates mammalian nuclear RNA N6-adenosine methylation. Nat Chem Biol. 10:93–95. 2014. View Article : Google Scholar : PubMed/NCBI | |
|
Lin Z, Hsu PJ, Xing X, Fang J, Lu Z, Zou Q, Zhang KJ, Zhang X, Zhou Y, Zhang T, et al: Mettl3-/Mettl14-mediated mRNA N6-methyladenosine modulates murine spermatogenesis. Cell Res. 27:1216–1230. 2017. View Article : Google Scholar : PubMed/NCBI | |
|
Yoon KJ, Ringeling FR, Vissers C, Jacob F, Pokrass M, Jimenez-Cyrus D, Su Y, Kim NS, Zhu Y, Zheng L, et al: Temporal control of mammalian cortical neurogenesis by m6A methylation. Cell. 171(877–889): e172017. | |
|
Horiuchi K, Umetani M, Minami T, Okayama H, Takada S, Yamamoto M, Aburatani H, Reid PC, Housman DE, Hamakubo T and Kodama T: Wilms' tumor 1-associating protein regulates G2/M transition through stabilization of cyclin A2 mRNA. Proc Natl Acad Sci USA. 103:17278–17283. 2006. View Article : Google Scholar : PubMed/NCBI | |
|
Gerken T, Girard CA, Tung YC, Webby CJ, Saudek V, Hewitson KS, Yeo GS, McDonough MA, Cunliffe S, McNeill LA, et al: The obesity associated FTO gene encodes a 2-oxoglutarate-dependent nucleic acid demethylase. Science. 318:1469–1472. 2007. View Article : Google Scholar : PubMed/NCBI | |
|
Fischer J, Koch L, Emmerling C, Vierkotten J, Peters T, Brüning JC and Rüther U: Inactivation of the Fto gene protects from obesity. Nature. 458:894–898. 2009. View Article : Google Scholar : PubMed/NCBI | |
|
Li L, Zang L, Zhang F, Chen J, Shen H, Shu L, Liang F, Feng C, Chen D, Tao H, et al: Fat mass and obesity-associated (FTO) protein regulates adult neurogenesis. Hum Mol Genet. 26:2398–2411. 2017. View Article : Google Scholar : PubMed/NCBI | |
|
Zheng G, Dahl JA, Niu Y, Fedorcsak P, Huang CM, Li CJ, Vågbø CB, Shi Y, Wang WL, Song SH, et al: ALKBH5 is a mammalian RNA demethylase that impacts RNA metabolism and mouse fertility. Mol Cell. 49:18–29. 2013. View Article : Google Scholar : PubMed/NCBI | |
|
Feng C, Liu Y, Wang G, Deng Z, Zhang Q, Wu W, Tong Y, Cheng C and Chen Z: Crystal structures of the human RNA demethylase Alkbh5 reveal basis for substrate recognition. J Biol Chem. 289:11571–11583. 2014. View Article : Google Scholar : PubMed/NCBI | |
|
Zhang Z, Theler D, Kaminska KH, Hiller M, de la Grange P, Pudimat R, Rafalska I, Heinrich B, Bujnicki JM, Allain FH and Stamm S: The YTH domain is novel RNA binding domain. J Biol Chem. 285:14701–14710. 2010. View Article : Google Scholar : PubMed/NCBI | |
|
Wang X, Zhao BS, Roundtree IA, Lu Z, Han D, Ma H, Weng X, Chen K, Shi H and He C: N(6)-methyladenosine modulates messenger RNA translation efficiency. Cell. 161:1388–1399. 2015. View Article : Google Scholar : PubMed/NCBI | |
|
Li A, Chen YS, Ping XL, Yang X, Xiao W, Yang Y, Sun HY, Zhu Q, Baidya P, Wang X, et al: Cytoplasmic m6A reader YTHDF3 promotes mRNA translation. Cell Res. 27:444–447. 2017. View Article : Google Scholar : PubMed/NCBI | |
|
Ivanova I, Much C, Di Giacomo M, Azzi C, Morgan M, Moreira PN, Monahan J, Carrieri C, Enright AJ and O'Carroll D: The RNA m6A reader YTHDF2 is essential for the post-transcriptional regulation of the maternal transcriptome and oocyte competence. Mol Cell. 67(1059–1067): e42017. | |
|
Zhao BS, Wang X, Beadell AV, Lu Z, Shi H, Kuuspalu A, Ho RK and He C: m6A-dependent maternal mRNA clearance facilitates zebrafish maternal-to-zygotic transition. Nature. 542:475–478. 2017. View Article : Google Scholar : PubMed/NCBI | |
|
De Kouchkovsky I and Abdul-Hay M: Acute myeloid leukemia: A comprehensive review and 2016 update. Blood Cancer J. 6:e4412016. View Article : Google Scholar : PubMed/NCBI | |
|
Touat M, Idbaih A, Sanson M and Ligon KL: Glioblastoma targeted therapy: Updated approaches from recent biological insights. Ann Oncol. 28:1457–1472. 2017. View Article : Google Scholar : PubMed/NCBI | |
|
Lieberman F: Glioblastoma update: Molecular biology, diagnosis, treatment, response assessment, and translational clinical trials. F1000Res. 6:18922017. View Article : Google Scholar : PubMed/NCBI | |
|
Saletore Y, Meyer K, Korlach J, Vilfan ID, Jaffrey S and Mason CE: The birth of the Epitranscriptome: Deciphering the function of RNA modifications. Genome Biol. 13:1752012. View Article : Google Scholar : PubMed/NCBI | |
|
Hussain S, Aleksic J, Blanco S, Dietmann S and Frye M: Characterizing 5-methylcytosine in the mammalian epitranscriptome. Genome Biol. 14:2152013. View Article : Google Scholar : PubMed/NCBI |
