Top

Published in:

Open Access 01-12-2018 | Review

Novel insights on m⁶A RNA methylation in tumorigenesis: a double-edged sword

Authors: Shaoyun Wang, Peiwei Chai, Ruobing Jia, Renbing Jia

Published in: Molecular Cancer | Issue 1/2018

Abstract

N6-methyladenosine (m⁶A), the most prevalent modification of mammalian RNA, has received increasing attention. Although m⁶A has been shown to be associated with biological activities, such as spermatogenesis modulation, cell spermatogenesis and pluripotency, Drosophila sex determination, and the control of T cell homeostasis and response to heat shock, little is known about its roles in cancer biology and cancer stem cells. Recent articles have noted that some genes have abnormal m⁶A expression after tumorigenesis, including genes ABS2, RARA, MYB, MYC, ADAM19 and FOX1. Abnormal changes in the m⁶A levels of these genes are closely related to tumour occurrence and development. In this review, we summarized the ‘dual edge weapon’ role of RNA methylation in the tumorigenesis. We discussed RNA methylation could lead to not only tumour progression but also tumour suppression. Moreover, we clarified that the abnormal changes in the m⁶A enrichment of specific loci contribute to tumour occurrence and development, thereby representing a novel anti-cancer strategy by restoration to balanced RNA methylation in tumour cells.

Machnicka MA, Milanowska K, Osman Oglou 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. 2013;41(Database issue):D262–7.PubMed

Desrosiers R, Friderici K, Rottman F. Identification of methylated nucleosides in messenger RNA from Novikoff hepatoma cells. Proc Natl Acad Sci U S A. 1974;71(10):3971–5.CrossRefPubMedPubMedCentral

Wei CM, Gershowitz A, Moss B. Methylated nucleotides block 5′ terminus of HeLa cell messenger RNA. Cell. 1975;4(4):379–86.CrossRefPubMed

Krug RM, Morgan MA, Shatkin AJ. Influenza viral mRNA contains internal N6-methyladenosine and 5′-terminal 7-methylguanosine in cap structures. J Virol. 1976;20(1):45–53.PubMedPubMedCentral

Sommer S, Salditt-Georgieff M, Bachenheimer S, Darnell JE, Furuichi Y, Morgan M, Shatkin AJ. The methylation of adenovirus-specific nuclear and cytoplasmic RNA. Nucleic Acids Res. 1976;3(3):749–65.CrossRefPubMedPubMedCentral

Kennedy TD, Lane BG. Wheat embryo ribonucleates. XIII. Methyl-substituted nucleoside constituents and 5′-terminal dinucleotide sequences in bulk poly(AR)-rich RNA from imbibing wheat embryos. Can J Biochem. 1979;57(6):927–31.CrossRefPubMed

Deng X, Chen K, Luo GZ, Weng X, Ji Q, Zhou T, He C. Widespread occurrence of N6-methyladenosine in bacterial mRNA. Nucleic Acids Res. 2015;43(13):6557–67.CrossRefPubMedPubMedCentral

Kane SE, Beemon K. Precise localization of m6A in Rous sarcoma virus RNA reveals clustering of methylation sites: implications for RNA processing. Mol Cell Biol. 1985;5(9):2298–306.CrossRefPubMedPubMedCentral

Dominissini D, Moshitch-Moshkovitz S, Schwartz S, Salmon-Divon M, Ungar L, Osenberg S, Cesarkas K, Jacob-Hirsch J, Amariglio N, Kupiec M, et al. Topology of the human and mouse m6A RNA methylomes revealed by m6A-seq. Nature. 2012;485(7397):201–6.CrossRefPubMed

10.

Bokar JA, Rath-Shambaugh ME, Ludwiczak R, Narayan P, Rottman F. Characterization and partial purification of mRNA N6-adenosine methyltransferase from HeLa cell nuclei. Internal mRNA methylation requires a multisubunit complex. J Biol Chem. 1994;269(26):17697–704.PubMed

11.

Bokar JA, Shambaugh ME, Polayes D, Matera AG, Rottman FM. Purification and cDNA cloning of the AdoMet-binding subunit of the human mRNA (N6-adenosine)-methyltransferase. RNA. 1997;3(11):1233–47.PubMedPubMedCentral

12.

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. 2014;10(2):93–5.CrossRefPubMed

13.

Schwartz S, Mumbach MR, Jovanovic M, Wang T, Maciag K, Bushkin GG, Mertins P, Ter-Ovanesyan D, Habib N, Cacchiarelli D, et al. Perturbation of m6A writers reveals two distinct classes of mRNA methylation at internal and 5′ sites. Cell Rep. 2014;8(1):284–96.CrossRefPubMedPubMedCentral

14.

Visvanathan A, Somasundaram K. mRNA traffic control reviewed: N6-Methyladenosine (m(6) A) takes the Driver’s seat. Bioessays. 2018;40(1)

15.

Wen J, Lv R, Ma H, Shen H, He C, Wang J, Jiao F, Liu H, Yang P, Tan L, et al. Zc3h13 regulates nuclear RNA m(6)A methylation and mouse embryonic stem cell self-renewal. Mol Cell. 2018;69(6):1028–38. e1026CrossRefPubMed

16.

Ruszkowska A, Ruszkowski M, Dauter Z, Brown JA. Structural insights into the RNA methyltransferase domain of METTL16. Sci Rep. 2018;8(1):5311.CrossRefPubMedPubMedCentral

17.

Jia G, Fu Y, Zhao X, Dai Q, Zheng G, Yang Y, Yi C, Lindahl T, Pan T, Yang YG, et al. N6-methyladenosine in nuclear RNA is a major substrate of the obesity-associated FTO. Nat Chem Biol. 2011;7(12):885–7.CrossRefPubMedPubMedCentral

18.

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. 2007;318(5855):1469–72.CrossRefPubMedPubMedCentral

19.

Zheng G, Dahl JA, Niu Y, Fedorcsak P, Huang CM, Li CJ, Vagbo CB, Shi Y, Wang WL, Song SH, et al. ALKBH5 is a mammalian RNA demethylase that impacts RNA metabolism and mouse fertility. Mol Cell. 2013;49(1):18–29.CrossRefPubMed

20.

Luo S, Tong L. Molecular basis for the recognition of methylated adenines in RNA by the eukaryotic YTH domain. Proc Natl Acad Sci U S A. 2014;111(38):13834–9.CrossRefPubMedPubMedCentral

21.

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. 2014;505(7481):117–20.CrossRefPubMed

22.

Xu C, Wang X, Liu K, Roundtree IA, Tempel W, Li Y, Lu Z, He C, Min J. Structural basis for selective binding of m6A RNA by the YTHDC1 YTH domain. Nat Chem Biol. 2014;10(11):927–9.CrossRefPubMed

23.

Zhu T, Roundtree IA, Wang P, Wang X, Wang L, Sun C, Tian Y, Li J, He C, Xu Y. Crystal structure of the YTH domain of YTHDF2 reveals mechanism for recognition of N6-methyladenosine. Cell Res. 2014;24(12):1493–6.CrossRefPubMedPubMedCentral

24.

Wang X, Zhao BS, Roundtree IA, Lu Z, Han D, Ma H, Weng X, Chen K, Shi H, He C. N(6)-methyladenosine modulates messenger RNA translation efficiency. Cell. 2015;161(6):1388–99.CrossRefPubMedPubMedCentral

25.

Xiao W, Adhikari S, Dahal U, Chen YS, Hao YJ, Sun BF, Sun HY, Li A, Ping XL, Lai WY, et al. Nuclear m(6)A reader YTHDC1 regulates mRNA splicing. Mol Cell. 2016;61(4):507–19.CrossRefPubMed

26.

Alarcon CR, Goodarzi H, Lee H, Liu X, Tavazoie S, Tavazoie SF. HNRNPA2B1 is a mediator of m(6)A-dependent nuclear RNA processing events. Cell. 2015;162(6):1299–308.CrossRefPubMedPubMedCentral

27.

Liu N, Dai Q, Zheng G, He C, Parisien M, Pan T. N(6)-methyladenosine-dependent RNA structural switches regulate RNA-protein interactions. Nature. 2015;518(7540):560–4.CrossRefPubMedPubMedCentral

28.

Zhou J, Wan J, Gao X, Zhang X, Jaffrey SR, Qian SB. Dynamic m(6)A mRNA methylation directs translational control of heat shock response. Nature. 2015;526(7574):591–4.CrossRefPubMedPubMedCentral

29.

Huang H, Weng H, Sun W, Qin X, Shi H, Wu H, Zhao BS, Mesquita A, Liu C, Yuan CL, et al. Recognition of RNA N(6)-methyladenosine by IGF2BP proteins enhances mRNA stability and translation. Nat Cell Biol. 2018;20(3):285–95.CrossRefPubMedPubMedCentral

30.

Arguello AE, DeLiberto AN, Kleiner RE. RNA chemical proteomics reveals the N(6)-Methyladenosine (m(6)A)-regulated protein-RNA Interactome. J Am Chem Soc. 2017;139(48):17249–52.CrossRefPubMed

31.

Ni TK, Elman JS, Jin DX, Gupta PB, Kuperwasser C. Premature polyadenylation of MAGI3 is associated with diminished N6-methyladenosine in its large internal exon. Sci Rep. 2018;8(1)

32.

Xiang JF, Yang Q, Liu CX, Wu M, Chen LL, Yang L. N(6)-Methyladenosines Modulate A-to-I RNA Editing. Mol Cell. 2018;69(1):126–135.e126.CrossRefPubMed

33.

Yang D, Qiao J, Wang G, Lan Y, Li G, Guo X, Xi J, Ye D, Zhu S, Chen W, et al. N6-Methyladenosine modification of lincRNA 1281 is critically required for mESC differentiation potential. Nucleic Acids Res. 2018;46(8):3906–20.CrossRefPubMedPubMedCentral

34.

Shima H, Matsumoto M, Ishigami Y, Ebina M, Muto A, Sato Y, Kumagai S, Ochiai K, Suzuki T, Igarashi K. S -Adenosylmethionine synthesis is regulated by selective N 6 -adenosine methylation and mRNA degradation involving METTL16 and YTHDC1. Cell Rep. 2017;21(12):3354–63.CrossRefPubMed

35.

Clermont Y. Kinetics of spermatogenesis in mammals: seminiferous epithelium cycle and spermatogonial renewal. Physiol Rev. 1972;52(1):198–236.CrossRefPubMed

36.

Takada K, Jameson SC. Naive T cell homeostasis: from awareness of space to a sense of place. Nat Rev Immunol. 2009;9(12):823–32.CrossRefPubMed

37.

Aguilo F, Zhang F, Sancho A, Fidalgo M, Di Cecilia S, Vashisht A, Lee DF, Chen CH, Rengasamy M, Andino B, et al. Coordination of m(6)A mRNA methylation and gene transcription by ZFP217 regulates pluripotency and reprogramming. Cell Stem Cell. 2015;17(6):689–704.CrossRefPubMedPubMedCentral

38.

Haussmann IU, Bodi Z, Sanchez-Moran E, Mongan NP, Archer N, Fray RG, Soller M. m(6)A potentiates Sxl alternative pre-mRNA splicing for robust Drosophila sex determination. Nature. 2016;540(7632):301–4.CrossRefPubMed

39.

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 N(6)-methyladenosine modulates murine spermatogenesis. Cell Res. 2017;27(10):1216–30.CrossRefPubMedPubMedCentral

40.

Li HB, Tong J, Zhu S, Batista PJ, Duffy EE, Zhao J, Bailis W, Cao G, Kroehling L, Chen Y, et al. m(6)A mRNA methylation controls T cell homeostasis by targeting the IL-7/STAT5/SOCS pathways. Nature. 2017;548(7667):338–42.CrossRefPubMedPubMedCentral

41.

Penalva LO, Ruiz MF, Ortega A, Granadino B, Vicente L, Segarra C, Valcarcel J, Sanchez L. The Drosophila fl(2)d gene, required for female-specific splicing of Sxl and tra pre-mRNAs, encodes a novel nuclear protein with a HQ-rich domain. Genetics. 2000;155(1):129–39.PubMedPubMedCentral

42.

Niessen M, Schneiter R, Nothiger R. Molecular identification of virilizer, a gene required for the expression of the sex-determining gene sex-lethal in Drosophila melanogaster. Genetics. 2001;157(2):679–88.PubMedPubMedCentral

43.

Horiuchi K, Kawamura T, Iwanari H, Ohashi R, Naito M, Kodama T, Hamakubo T. Identification of Wilms’ tumor 1-associating protein complex and its role in alternative splicing and the cell cycle. J Biol Chem. 2013;288(46):33292–302.CrossRefPubMedPubMedCentral

44.

Fang NN, Chan GT, Zhu M, Comyn SA, Persaud A, Deshaies RJ, Rotin D, Gsponer J, Mayor T. Rsp5/Nedd4 is the main ubiquitin ligase that targets cytosolic misfolded proteins following heat stress. Nat Cell Biol. 2014;16(12):1227–37.CrossRefPubMedPubMedCentral

45.

Marcucci G, Mrozek K, Bloomfield CD. Molecular heterogeneity and prognostic biomarkers in adults with acute myeloid leukemia and normal cytogenetics. Curr Opin Hematol. 2005;12(1):68–75.CrossRefPubMed

46.

Chen J, Odenike O, Rowley JD. Leukaemogenesis: more than mutant genes. Nat Rev Cancer. 2010;10(1):23–36.CrossRefPubMedPubMedCentral

47.

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 N(6)-Methyladenosine RNA demethylase. Cancer Cell. 2017;31(1):127–41.CrossRefPubMed

48.

Weng H, Huang H, Wu H, Qin X, Zhao BS, Dong L, Shi H, Skibbe J, Shen C, Hu C, et al. METTL14 inhibits hematopoietic stem/progenitor differentiation and promotes Leukemogenesis via mRNA m(6)A modification. Cell Stem Cell. 2017

49.

Su R, Dong L, Li C, Nachtergaele S, Wunderlich M, Qing Y, Deng X, Wang Y, Weng X, Hu C, et al. R-2HG exhibits anti-tumor activity by targeting FTO/m(6)A/MYC/CEBPA signaling. Cell. 2018;172(1–2):90–105. e123CrossRefPubMed

50.

Vu LP, Pickering BF, Cheng Y, Zaccara S, Nguyen D, Minuesa G, Chou T, Chow A, Saletore Y, MacKay M, et al. The N(6)-methyladenosine (m(6)A)-forming enzyme METTL3 controls myeloid differentiation of normal hematopoietic and leukemia cells. Nat Med. 2017;23(11):1369–76.PubMedPubMedCentral

51.

Barbieri I, Tzelepis K, Pandolfini L, Shi J, Millan-Zambrano G, Robson SC, Aspris D, Migliori V, Bannister AJ, Han N, et al. Promoter-bound METTL3 maintains myeloid leukaemia by m(6)A-dependent translation control. Nature. 2017;552(7683):126–31.PubMed

52.

Bosch FX, Ribes J, Borras J. Epidemiology of primary liver cancer. Semin Liver Dis. 1999;19(3):271–85.CrossRefPubMed

53.

Schulze K, Imbeaud S, Letouze E, Alexandrov LB, Calderaro J, Rebouissou S, Couchy G, Meiller C, Shinde J, Soysouvanh F, et al. Exome sequencing of hepatocellular carcinomas identifies new mutational signatures and potential therapeutic targets. Nat Genet. 2015;47(5):505–11.CrossRefPubMedPubMedCentral

54.

Wong CM, Lee JM, Ching YP, Jin DY, Ng IO. Genetic and epigenetic alterations of DLC-1 gene in hepatocellular carcinoma. Cancer Res. 2003;63(22):7646–51.PubMed

55.

Wong CM, Ng YL, Lee JM, Wong CC, Cheung OF, Chan CY, Tung EK, Ching YP, Ng IO. Tissue factor pathway inhibitor-2 as a frequently silenced tumor suppressor gene in hepatocellular carcinoma. Hepatology. 2007;45(5):1129–38.CrossRefPubMed

56.

Villanueva A, Portela A, Sayols S, Battiston C, Hoshida Y, Mendez-Gonzalez J, Imbeaud S, Letouze E, Hernandez-Gea V, Cornella H, et al. DNA methylation-based prognosis and epidrivers in hepatocellular carcinoma. Hepatology. 2015;61(6):1945–56.CrossRefPubMed

57.

Au SL, Wong CC, Lee JM, Fan DN, Tsang FH, Ng IO, Wong CM. Enhancer of zeste homolog 2 epigenetically silences multiple tumor suppressor microRNAs to promote liver cancer metastasis. Hepatology. 2012;56(2):622–31.CrossRefPubMed

58.

Fan DN, Tsang FH, Tam AH, Au SL, Wong CC, Wei L, Lee JM, He X, Ng IO, Wong CM. Histone lysine methyltransferase, suppressor of variegation 3-9 homolog 1, promotes hepatocellular carcinoma progression and is negatively regulated by microRNA-125b. Hepatology. 2013;57(2):637–47.CrossRefPubMed

59.

Wei L, Chiu DK, Tsang FH, Law CT, Cheng CL, Au SL, Lee JM, Wong CC, Ng IO, Wong CM. Histone methyltransferase G9a promotes liver cancer development by epigenetic silencing of tumor suppressor gene RARRES3. J Hepatol. 2017;67(4):758–69.CrossRefPubMed

60.

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 METTL3 promotes liver cancer progression through YTHDF2 dependent post-transcriptional silencing of SOCS2. Hepatology. 2017

61.

Ma JZ, Yang F, Zhou CC, Liu F, Yuan JH, Wang F, Wang TT, Xu QG, Zhou WP, Sun SH. METTL14 suppresses the metastatic potential of hepatocellular carcinoma by modulating N(6) -methyladenosine-dependent primary MicroRNA processing. Hepatology. 2017;65(2):529–43.CrossRefPubMed

62.

Johnson DR, O'Neill BP. Glioblastoma survival in the United States before and during the temozolomide era. J Neuro-Oncol. 2012;107(2):359–64.CrossRef

63.

Stupp R, Hegi ME, Mason WP, van den Bent MJ, Taphoorn MJ, Janzer RC, Ludwin SK, Allgeier A, Fisher B, Belanger K, et al. Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial. Lancet Oncol. 2009;10(5):459–66.CrossRefPubMed

64.

Singh SK, Hawkins C, Clarke ID, Squire JA, Bayani J, Hide T, Henkelman RM, Cusimano MD, Dirks PB. Identification of human brain tumour initiating cells. Nature. 2004;432(7015):396–401.CrossRefPubMed

65.

Bao S, Wu Q, McLendon RE, Hao Y, Shi Q, Hjelmeland AB, Dewhirst MW, Bigner DD, Rich JN. Glioma stem cells promote radioresistance by preferential activation of the DNA damage response. Nature. 2006;444(7120):756–60.CrossRefPubMed

66.

Godlewski J, Newton HB, Chiocca EA, Lawler SE. MicroRNAs and glioblastoma; the stem cell connection. Cell Death Differ. 2010;17(2):221–8.CrossRefPubMed

67.

Sundar SJ, Hsieh JK, Manjila S, Lathia JD, Sloan A. The role of cancer stem cells in glioblastoma. Neurosurg Focus. 2014;37(6):E6.CrossRefPubMed

68.

Allegra A, Alonci A, Penna G, Innao V, Gerace D, Rotondo F, Musolino C. The cancer stem cell hypothesis: a guide to potential molecular targets. Cancer Investig. 2014;32(9):470–95.CrossRef

69.

Cui Q, Shi H, Ye P, Li L, Qu Q, Sun G, Sun G, Lu Z, Huang Y, Yang CG, et al. m(6)A RNA methylation regulates the self-renewal and tumorigenesis of glioblastoma stem cells. Cell Rep. 2017;18(11):2622–34.CrossRefPubMedPubMedCentral

70.

Zhang S, Zhao BS, Zhou A, Lin K, Zheng S, Lu Z, Chen Y, Sulman EP, Xie K, Bogler O, et al. m(6)A demethylase ALKBH5 maintains tumorigenicity of glioblastoma stem-like cells by sustaining FOXM1 expression and cell proliferation program. Cancer Cell. 2017;31(4):591–606. e596CrossRefPubMedPubMedCentral

71.

DeSantis CE, Bray F, Ferlay J, Lortet-Tieulent J, Anderson BO, Jemal A. International variation in female breast Cancer incidence and mortality rates. Cancer Epidemiol Biomark Prev. 2015;24(10):1495–506.CrossRef

72.

DeSantis CE, Ma J, Goding Sauer A, Newman LA, Jemal A. Breast cancer statistics, 2017, racial disparity in mortality by state. CA Cancer J Clin. 2017;67(6):439–48.CrossRefPubMed

73.

O'Shaughnessy J. Extending survival with chemotherapy in metastatic breast cancer. Oncologist. 2005;10(Suppl 3):20–9.CrossRefPubMed

74.

Zhang C, Zhi WI, Lu H, Samanta D, Chen I, Gabrielson E, Semenza GL. Hypoxia-inducible factors regulate pluripotency factor expression by ZNF217- and ALKBH5-mediated modulation of RNA methylation in breast cancer cells. Oncotarget. 2016;7(40):64527–42.PubMedPubMedCentral

75.

Cai X, Wang X, Cao C, Gao Y, Zhang S, Yang Z, Liu Y, Zhang X, Zhang W, Ye L. HBXIP-elevated methyltransferase METTL3 promotes the progression of breast cancer via inhibiting tumor suppressor let-7g. Cancer Lett. 2018;415:11–9.CrossRefPubMed

76.

Small W Jr, Bacon MA, Bajaj A, Chuang LT, Fisher BJ, Harkenrider MM, Jhingran A, Kitchener HC, Mileshkin LR, Viswanathan AN, et al. Cervical cancer: a global health crisis. Cancer. 2017;123(13):2404–12.CrossRefPubMed

77.

Verma J, Monk BJ, Wolfson AH. New strategies for multimodality therapy in treating locally advanced cervix Cancer. Semin Radiat Oncol. 2016;26(4):344–8.CrossRefPubMed

78.

Tewari KS, Monk BJ. New strategies in advanced cervical cancer: from angiogenesis blockade to immunotherapy. Clin Cancer Res. 2014;20(21):5349–58.CrossRefPubMed

79.

Zhou S, Bai ZL, Xia D, Zhao ZJ, Zhao R, Wang YY, Zhe H. FTO regulates the chemo-radiotherapy resistance of cervical squamous cell carcinoma (CSCC) by targeting beta-catenin through mRNA demethylation. Mol Carcinog. 2018;57(5):590–7.CrossRefPubMed

80.

Molina JR, Yang P, Cassivi SD, Schild SE, Adjei AA. Non-small cell lung cancer: epidemiology, risk factors, treatment, and survivorship. Mayo Clin Proc. 2008;83(5):584–94.CrossRefPubMedPubMedCentral

81.

Hussain S. Nanomedicine for treatment of lung Cancer. Adv Exp Med Biol. 2016;890:137–47.CrossRefPubMed

82.

Araz O, Ucar EY, Meral M, Yalcin A, Acemoglu H, Dogan H, Karaman A, Aydin Y, Gorguner M, Akgun M. Frequency of class I and II HLA alleles in patients with lung cancer according to chemotherapy response and 5-year survival. Clin Respir J. 2015;9(3):297–304.CrossRefPubMed

83.

Latimer KM, Mott TF. Lung cancer: diagnosis, treatment principles, and screening. Am Fam Physician. 2015;91(4):250–6.PubMed

84.

Lin S, Choe J, Du P, Triboulet R, Gregory RI. The m(6)A methyltransferase METTL3 promotes translation in human Cancer cells. Mol Cell. 2016;62(3):335–45.CrossRefPubMedPubMedCentral

85.

Du M, Zhang Y, Mao Y, Mou J, Zhao J, Xue Q, Wang D, Huang J, Gao S, Gao Y. MiR-33a suppresses proliferation of NSCLC cells via targeting METTL3 mRNA. Biochem Biophys Res Commun. 2017;482(4):582–9.CrossRefPubMed

86.

Du Y, Hou G, Zhang H, Dou J, He J, Guo Y, Li L, Chen R, Wang Y, Deng R, et al. SUMOylation of the m6A-RNA methyltransferase METTL3 modulates its function. Nucleic Acids Res. 2018;46(10):5195–208.CrossRefPubMedPubMedCentral

Title: Novel insights on m6A RNA methylation in tumorigenesis: a double-edged sword
Authors: Shaoyun Wang
Peiwei Chai
Ruobing Jia
Renbing Jia
Publication date: 01-12-2018
Publisher: BioMed Central
Published in: Molecular Cancer / Issue 1/2018
Electronic ISSN: 1476-4598
DOI: https://doi.org/10.1186/s12943-018-0847-4

Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras

Prof. Fabrice Barlesi

Developed by: Springer Medicine

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 1/2018

Posttranscriptional upregulation of HER3 by HER2 mRNA induces trastuzumab resistance in breast cancer

Oncogenic fusion proteins adopt the insulin-like growth factor signaling pathway

Nischarin regulates focal adhesion and Invadopodia formation in breast cancer cells

Comparative proteogenomic analysis of right-sided colon cancer, left-sided colon cancer and rectal cancer reveals distinct mutational profiles

Engineering chimeric antigen receptor-T cells for cancer treatment

Wnt-signaling enhances neural crest migration of melanoma cells and induces an invasive phenotype

Keynote webinar | Spotlight on antibody–drug conjugates in cancer