Epigenetic modifications in acute myeloid leukemia: The emerging role of circular RNAs (Review)

Issah,Mohammed Awal; Wu,Dansen; Zhang,Feng; Zheng,Weili; Liu,Yanquan; Fu,Haiying; Zhou,Huarong; Chen,Rong; Shen,Jianzhen

doi:10.3892/ijo.2021.5287

Epigenetic modifications in acute myeloid leukemia: The emerging role of circular RNAs (Review)

Authors:
- Mohammed Awal Issah
- Dansen Wu
- Feng Zhang
- Weili Zheng
- Yanquan Liu
- Haiying Fu
- Huarong Zhou
- Rong Chen
- Jianzhen Shen
View Affiliations

Affiliations: Fujian Institute of Hematology, Fujian Medical Center of Hematology, Clinical Research Center for Hematological Malignancies of Fujian Province, Fuzhou, Fujian 350001, P.R. China, Medical Intensive Care Unit, Fujian Provincial Hospital, Fuzhou, Fujian 350001, P.R. China
Published online on: November 17, 2021 https://doi.org/10.3892/ijo.2021.5287
Article Number: 107
Copyright: © Issah et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Canonical epigenetic modifications, which include histone modification, chromatin remodeling and DNA methylation, play key roles in numerous cellular processes. Epigenetics underlies how cells that posses DNA with similar sequences develop into different cell types with different functions in an organism. Earlier epigenetic research has primarily been focused at the chromatin level. However, the number of studies on epigenetic modifications of RNA, such as N¹‑methyladenosine, 2'‑O‑ribosemethylation, inosine, 5‑methylcytidine, N⁶‑methyladenosine (m⁶A) and pseudouridine, has seen an increase. Circular RNAs (circRNAs), a type of RNA species that lacks a 5' cap or 3' poly(A) tail, are abundantly expressed in acute myeloid leukemia (AML) and may regulate disease progression. circRNAs possess various functions, including microRNA sponging, gene transcription regulation and RNA‑binding protein interaction. Furthermore, circRNAs are m⁶A methylated in other types of cancer, such as colorectal and hypopharyngeal squamous cell cancers. Therefore, the critical roles of circRNA epigenetic modifications, particularly m⁶A, and their possible involvement in AML are discussed in the present review. Epigenetic modification of circRNAs may become a diagnostic and therapeutic target for AML in the future.

View Figures

View References

1	Chen LL and Yang L: Regulation of circRNA biogenesis. RNA Biol. 12:381–388. 2015. View Article : Google Scholar : PubMed/NCBI
2	Bartel DP: MicroRNAs: Target recognition and regulatory functions. Cell. 136:215–233. 2009. View Article : Google Scholar : PubMed/NCBI
3	Dong Y, He D, Peng Z, Peng W, Shi W, Wang J, Li B, Zhang C and Duan C: Circular RNAs in cancer: An emerging key player. J Hematol Oncol. 10:22017. View Article : Google Scholar
4	Memczak S, Jens M, Elefsinioti A, Torti F, Krueger J, Rybak A, Maier L, Mackowiak S, Gregersen LH, Munschauer M, et al: Circular RNAs are a large class of animal RNAs with regulatory potency. Nature. 495:333–338. 2013. View Article : Google Scholar : PubMed/NCBI
5	Zhang Y, Zhang XO, Chen T, Xiang JF, Yin QF, Xing YH, Zhu S, Yang L and Chen LL: Circular intronic long noncoding RNAs. Mol Cell. 51:792–806. 2013. View Article : Google Scholar : PubMed/NCBI
6	Dupont C, Armant DR and Brenner CA: Epigenetics: Definition, mechanisms and clinical perspective. Semin Reprod Med. 27:351–357. 2009. View Article : Google Scholar :
7	Bolisetty MT and Graveley BR: Circuitous route to transcription regulation. Mol Cell. 51:705–706. 2013. View Article : Google Scholar : PubMed/NCBI
8	Suzuki H and Tsukahara T: A view of pre-mRNA splicing from RNase R resistant RNAs. Int J Mol Sci. 15:9331–9342. 2014. View Article : Google Scholar :
9	Jeck WR, Sorrentino JA, Wang K, Slevin MK, Burd CE, Liu J, Marzluff WF and Sharpless NE: Circular RNAs are abundant, conserved, and associated with ALU repeats. RNA. 19:141–157. 2013. View Article : Google Scholar
10	Gruner H, Cortés-López M, Cooper DA, Bauer M and Miura P: CircRNA accumulation in the aging mouse brain. Sci Rep. 6:389072016. View Article : Google Scholar : PubMed/NCBI
11	Hansen TB, Jensen TI, Clausen BH, Bramsen JB, Finsen B, Damgaard CK and Kjems J: Natural RNA circles function as efficient microRNA sponges. Nature. 495:384–388. 2013. View Article : Google Scholar
12	Ashwal-Fluss R, Meyer M, Pamudurti NR, Ivanov A, Bartok O, Hanan M, Evantal N, Memczak S, Rajewsky N and Kadener S: CircRNA biogenesis competes with pre-mRNA splicing. Mol Cell. 56:55–66. 2014. View Article : Google Scholar : PubMed/NCBI
13	Li Z, Huang C, Bao C, Chen L, Lin M, Wang X, Zhong G, Yu B, Hu W, Dai L, et al: Exon-intron circular RNAs regulate transcription in the nucleus. Nat Struct Mol Biol. 22:256–264. 2015. View Article : Google Scholar : PubMed/NCBI
14	Meng S, Zhou H, Feng Z, Xu Z, Tang Y, Li P and Wu M: CircRNA: Functions and properties of a novel potential biomarker for cancer. Mol Cancer. 16:942017. View Article : Google Scholar
15	Yang Y, Fan X, Mao M, Song X, Wu P, Zhang Y, Jin Y, Yang Y, Chen LL, Wang Y, et al: Extensive translation of circular RNAs driven by N6-methyladenosine. Cell Res. 27:626–641. 2017. View Article : Google Scholar : PubMed/NCBI
16	Zhou C, Molinie B, Daneshvar K, Pondick JV, Wang J, Van Wittenberghe N, Xing Y, Giallourakis CC and Mullen AC: Genome-wide maps of m6A circRNAs identify widespread and cell-type-specific methylation patterns that are distinct from mRNAs. Cell Rep. 20:2262–2276. 2017. View Article : Google Scholar
17	Gapp K, Woldemichael BT, Bohacek J and Mansuy IM: Epigenetic regulation in neurodevelopment and neurodegenerative diseases. Neuroscience. 264:99–111. 2014. View Article : Google Scholar
18	Trowbridge JJ, Snow JW, Kim J and Orkin SH: DNA methyltransferase 1 is essential for and uniquely regulates hematopoietic stem and progenitor cells. Cell Stem Cell. 5:442–449. 2009. View Article : Google Scholar : PubMed/NCBI
19	Harman MF and Martín MG: Epigenetic mechanisms related to cognitive decline during aging. J Neurosci Res. 98:234–246. 2020. View Article : Google Scholar
20	Feinberg AP and Tycko B: The history of cancer epigenetics. Nat Rev Cancer. 4:143–153. 2004. View Article : Google Scholar : PubMed/NCBI
21	Jones PA: Functions of DNA methylation: Islands, start sites, gene bodies and beyond. Nat Rev Genet. 13:484–492. 2012. View Article : Google Scholar : PubMed/NCBI
22	Hájková H, Marková J, Haškovec C, Šárová I, Fuchs O, Kostečka A, Cetkovský P, Michalová K and Schwarz J: Decreased DNA methylation in acute myeloid leukemia patients with DNMT3A mutations and prognostic implications of DNA methylation. Leuk Res. 36:1128–1133. 2012. View Article : Google Scholar : PubMed/NCBI
23	Bröske AM, Vockentanz L, Kharazi S, Huska MR, Mancini E, Scheller M, Kuhl C, Enns A, Prinz M, Jaenisch R, et al: DNA methylation protects hematopoietic stem cell multipotency from myeloerythroid restriction. Nat Genet. 41:1207–1215. 2009. View Article : Google Scholar : PubMed/NCBI
24	Bock C, Beerman I, Lien WH, Smith ZD, Gu H, Boyle P, Gnirke A, Fuchs E, Rossi DJ and Meissner A: DNA methylation dynamics during in vivo differentiation of blood and skin stem cells. Mol Cell. 47:633–647. 2012. View Article : Google Scholar : PubMed/NCBI
25	Hodges E, Molaro A, Dos Santos CO, Thekkat P, Song Q, Uren PJ, Park J, Butler J, Rafii S, McCombie WR, et al: Directional DNA methylation changes and complex intermediate states accompany lineage specificity in the adult hematopoietic compartment. Mol Cell. 44:17–28. 2011. View Article : Google Scholar
26	Hogart A, Lichtenberg J, Ajay SS, Anderson S; NIH Intramural Sequencing Center; Margulies EH and Bodine DM: Genome-wide DNA methylation profiles in hematopoietic stem and progenitor cells reveal overrepresentation of ETS transcription factor binding sites. Genome Res. 22:1407–1418. 2012. View Article : Google Scholar : PubMed/NCBI
27	Tadokoro Y, Ema H, Okano M, Li E and Nakauchi H: De novo DNA methyltransferase is essential for self-renewal, but not for differentiation, in hematopoietic stem cells. J Exp Med. 204:715–722. 2007. View Article : Google Scholar :
28	Jiang Y, Dunbar A, Gondek LP, Mohan S, Rataul M, O'Keefe C, Sekeres M, Saunthararajah Y and Maciejewski JP: Aberrant DNA methylation is a dominant mechanism in MDS progression to AML. Blood. 113:1315–1325. 2009. View Article : Google Scholar :
29	Chen J, Odenike O and Rowley JD: Leukaemogenesis: More than mutant genes. Nat Rev Cancer. 10:23–36. 2010. View Article : Google Scholar
30	Schoofs T, Berdel WE and Müller-Tidow C: Origins of aberrant DNA methylation in acute myeloid leukemia. Leukemia. 28:1–14. 2014. View Article : Google Scholar
31	Figueroa ME, Lugthart S, Li Y, Erpelinck-Verschueren C, Deng X, Christos PJ, Schifano E, Booth J, van Putten W, Skrabanek L, et al: DNA methylation signatures identify biologically distinct subtypes in acute myeloid leukemia. Cancer Cell. 17:13–27. 2010. View Article : Google Scholar :
32	Cole CB, Verdoni AM, Ketkar S, Leight ER, Russler-Germain DA, Lamprecht TL, Demeter RT, Magrini V and Ley TJ: PML-RARA requires DNA methyltransferase 3A to initiate acute promyelocytic leukemia. J Clin Invest. 126:85–98. 2016. View Article : Google Scholar :
33	Ley TJ, Miller C, Ding L, Raphael BJ, Mungall AJ, Robertson AG, Hoadley K, Triche TJ Jr, Laird PW, Batty JD, et al: Genomic and epigenomic landscapes of adult de novo acute myeloid leukemia. N Engl J Med. 368:2059–2074. 2013. View Article : Google Scholar : PubMed/NCBI
34	Thol F, Damm F, Lüdeking A, Winschel C, Wagner K, Morgan M, Yun H, Göhring G, Schlegelberger B, Hoelzer D, et al: Incidence and prognostic influence of DNMT3A mutations in acute myeloid leukemia. J Clin Oncol. 29:2889–2896. 2011. View Article : Google Scholar : PubMed/NCBI
35	Marková J, Michková P, Burčková K, Březinová J, Michalová K, Dohnalová A, Maaloufová JS, Soukup P, Vítek A, Cetkovský P and Schwarz J: Prognostic impact of DNMT3A mutations in patients with intermediate cytogenetic risk profile acute myeloid leukemia. Eur J Haematol. 88:128–135. 2012. View Article : Google Scholar
36	Alvarez S, Suela J, Valencia A, Fernández A, Wunderlich M, Agirre X, Prósper F, Martín-Subero JI, Maiques A, Acquadro F, et al: DNA methylation profiles and their relationship with cytogenetic status in adult acute myeloid leukemia. PLoS One. 5:e121972010. View Article : Google Scholar : PubMed/NCBI
37	Akalin A, Garrett-Bakelman FE, Kormaksson M, Busuttil J, Zhang L, Khrebtukova I, Milne TA, Huang Y, Biswas D, Hess JL, et al: Base-pair resolution DNA methylation sequencing reveals profoundly divergent epigenetic landscapes in acute myeloid leukemia. PLoS Genet. 8:e10027812012. View Article : Google Scholar :
38	Cimmino L, Dawlaty MM, Ndiaye-Lobry D, Yap YS, Bakogianni S, Yu Y, Bhattacharyya S, Shaknovich R, Geng H, Lobry C, et al: Erratum: TET1 is a tumor suppressor of hematopoietic malignancy. Nat Immunol. 16:8892015. View Article : Google Scholar
39	Moran-Crusio K, Reavie L, Shih A, Abdel-Wahab O, Ndiaye-Lobry D, Lobry C, Figueroa ME, Vasanthakumar A, Patel J, Zhao X, et al: Tet2 loss leads to increased hematopoietic stem cell self-renewal and myeloid transformation. Cancer Cell. 20:11–24. 2011. View Article : Google Scholar : PubMed/NCBI
40	Li Z, Cai X, Cai CL, Wang J, Zhang W, Petersen BE, Yang FC and Xu M: Deletion of Tet2 in mice leads to dysregulated hematopoietic stem cells and subsequent development of myeloid malignancies. Blood. 118:4509–4518. 2011. View Article : Google Scholar : PubMed/NCBI
41	Abdel-Wahab O, Mullally A, Hedvat C, Garcia-Manero G, Patel J, Wadleigh M, Malinge S, Yao J, Kilpivaara O, Bhat R, et al: Genetic characterization of TET1, TET2, and TET3 alterations in myeloid malignancies. Blood. 114:144–147. 2009. View Article : Google Scholar :
42	Tefferi A, Lim KH, Abdel-Wahab O, Lasho TL, Patel J, Patnaik MM, Hanson CA, Pardanani A, Gilliland DG and Levine RL: Detection of mutant TET2 in myeloid malignancies other than myeloproliferative neoplasms: CMML, MDS, MDS/MPN and AML. Leukemia. 23:1343–1345. 2009. View Article : Google Scholar : PubMed/NCBI
43	Bacher U, Haferlach C, Schnittger S, Kohlmann A, Kern W and Haferlach T: Mutations of the TET2 and CBL genes: Novel molecular markers in myeloid malignancies. Ann Hematol. 89:643–652. 2010. View Article : Google Scholar : PubMed/NCBI
44	Sato H, Wheat JC, Steidl U and Ito K: DNMT3A and TET2 in the pre-leukemic phase of hematopoietic disorders. Front Oncol. 6:1872016. View Article : Google Scholar : PubMed/NCBI
45	Chan SM and Majeti R: Role of DNMT3A, TET2, and IDH1/2 mutations in pre-leukemic stem cells in acute myeloid leukemia. Int J Hematol. 98:648–657. 2013. View Article : Google Scholar : PubMed/NCBI
46	Weissmann S, Alpermann T, Grossmann V, Kowarsch A, Nadarajah N, Eder C, Dicker F, Fasan A, Haferlach C, Haferlach T, et al: Landscape of TET2 mutations in acute myeloid leukemia. Leukemia. 26:934–942. 2012. View Article : Google Scholar
47	Shih AH, Jiang Y, Meydan C, Shank K, Pandey S, Barreyro L, Antony-Debre I, Viale A, Socci N, Sun Y, et al: Mutational cooperativity linked to combinatorial epigenetic gain of function in acute myeloid leukemia. Cancer Cell. 27:502–515. 2015. View Article : Google Scholar
48	Rasmussen KD, Jia G, Johansen JV, Pedersen MT, Rapin N, Bagger F, Porse BT, Bernard OA, Christensen J, Helin K, et al: Loss of TET2 in hematopoietic cells leads to DNA hypermethylation of active enhancers and induction of leukemogenesis. Genes Dev. 29:910–922. 2015. View Article : Google Scholar : PubMed/NCBI
49	Berger SL: The complex language of chromatin regulation during transcription. Nature. 447:407–412. 2007. View Article : Google Scholar : PubMed/NCBI
50	Podobinska M, Szablowska-Gadomska I, Augustyniak J, Sandvig I, Sandvig A and Buzanska L: Epigenetic modulation of stem cells in neurodevelopment: The role of methylation and acetylation. Front Cell Neurosci. 11:232017. View Article : Google Scholar : PubMed/NCBI
51	Zhang Y, Gilquin B, Khochbin S and Matthias P: Two catalytic domains are required for protein deacetylation. J Biol Chem. 281:2401–2404. 2006. View Article : Google Scholar
52	Uchida T, Kinoshita T, Nagai H, Nakahara Y, Saito H, Hotta T and Murate T: Hypermethylation of the p15INK4B gene in myelodysplastic syndromes. Blood. 90:1403–1409. 1997. View Article : Google Scholar : PubMed/NCBI
53	Melki JR, Vincent PC and Clark SJ: Concurrent DNA hyper-methylation of multiple genes in acute myeloid leukemia. Cancer Res. 59:3730–3740. 1999.PubMed/NCBI
54	Herman JG, Jen J, Merlo A and Baylin SB: Hypermethylation-associated inactivation indicates a tumor suppressor role for p15INK4B. Cancer Res. 56:722–727. 1996.PubMed/NCBI
55	Jenuwein T: Translating the histone code. Science. 293:1074–1080. 2001. View Article : Google Scholar : PubMed/NCBI
56	van Dijk AD, Hu CW, de Bont ESJM, Qiu Y, Hoff FW, Yoo SY, Coombes KR, Qutub AA and Kornblau SM: Histone modification patterns using RPPA-based profiling predict outcome in acute myeloid leukemia patients. Proteomics. 18:17003792018. View Article : Google Scholar
57	Zaghlool A, Halvardson J, Zhao JJ, Etemadikhah M, Kalushkova A, Konska K, Jernberg-Wiklund H, Thuresson AC and Feuk L: A role for the chromatin-remodeling factor BAZ1A in neurodevelopment. Hum Mutat. 37:964–975. 2016. View Article : Google Scholar : PubMed/NCBI
58	Olave IA, Reck-Peterson SL and Crabtree GR: Nuclear actin and actin-related proteins in chromatin remodeling. Annu Rev Biochem. 71:755–781. 2002. View Article : Google Scholar
59	Choi KY, Yoo M and Han JH: Toward understanding the role of the neuron-specific BAF chromatin remodeling complex in memory formation. Exp Mol Med. 47:e1552015. View Article : Google Scholar : PubMed/NCBI
60	Redner RL, Wang J and Liu JM: Chromatin remodeling and leukemia: New therapeutic paradigms. Blood. 94:417–428. 1999. View Article : Google Scholar
61	Sperlazza J, Rahmani M, Beckta J, Aust M, Hawkins E, Wang SZ, Zu Zhu S, Podder S, Dumur C, Archer K, et al: Depletion of the chromatin remodeler CHD4 sensitizes AML blasts to genotoxic agents and reduces tumor formation. Blood. 126:1462–1472. 2015. View Article : Google Scholar
62	Denslow SA and Wade PA: The human Mi-2/NuRD complex and gene regulation. Oncogene. 26:5433–5438. 2007. View Article : Google Scholar
63	D'Alesio C, Punzi S, Cicalese A, Fornasari L, Furia L, Riva L, Carugo A, Curigliano G, Criscitiello C, Pruneri G, et al: RNAi screens identify CHD4 as an essential gene in breast cancer growth. Oncotarget. 7:80901–80915. 2016. View Article : Google Scholar : PubMed/NCBI
64	O'Shaughnessy A and Hendrich B: CHD4 in the DNA-damage response and cell cycle progression: Not so NuRDy now. Biochem Soc Trans. 41:777–782. 2013. View Article : Google Scholar :
65	Polo SE, Kaidi A, Baskcomb L, Galanty Y and Jackson SP: Regulation of DNA-damage responses and cell-cycle progression by the chromatin remodelling factor CHD4. EMBO J. 29:3130–3139. 2010. View Article : Google Scholar :
66	Xia L, Huang W, Bellani M, Seidman MM, Wu K, Fan D, Nie Y, Cai Y, Zhang YW, Yu LR, et al: CHD4 has oncogenic functions in initiating and maintaining epigenetic suppression of multiple tumor suppressor genes. Cancer Cell. 31:653–668.e7. 2017. View Article : Google Scholar :
67	Heshmati Y, Türköz G, Harisankar A, Kharazi S, Boström J, Dolatabadi EK, Krstic A, Chang D, Månsson R, Altun M, et al: The chromatin-remodeling factor CHD4 is required for maintenance of childhood acute myeloid leukemia. Haematologica. 103:1169–1181. 2018. View Article : Google Scholar :
68	Zhen T, Kwon EM, Zhao L, Hsu J, Hyde RK, Lu Y, Alemu L, Speck NA and Liu PP: Chd7 deficiency delays leukemogenesis in mice induced by Cbfb-MYH11. Blood. 130:2431–2442. 2017. View Article : Google Scholar : PubMed/NCBI
69	Fazi F, Racanicchi S, Zardo G, Starnes LM, Mancini M, Travaglini L, Diverio D, Ammatuna E, Cimino G, Lo-Coco F, et al: Epigenetic silencing of the myelopoiesis regulator microRNA-223 by the AML1/ETO oncoprotein. Cancer Cell. 12:457–466. 2007. View Article : Google Scholar
70	Li Y, Gao L, Luo X, Wang L, Gao X, Wang W, Sun J, Dou L, Li J, Xu C, et al: Epigenetic silencing of microRNA-193a contributes to leukemogenesis in t(8;21) acute myeloid leukemia by activating the PTEN/PI3K signal pathway. Blood. 121:499–509. 2013. View Article : Google Scholar
71	Berger SL, Kouzarides T, Shiekhattar R and Shilatifard A: An operational definition of epigenetics. Genes Dev. 23:781–783. 2009. View Article : Google Scholar : PubMed/NCBI
72	Sun WJ, Li JH, Liu S, Wu J, Zhou H, Qu LH and Yang JH: RMBase: A resource for decoding the landscape of RNA modifications from high-throughput sequencing data. Nucleic Acids Res. 44:D259–D265. 2016. View Article : Google Scholar :
73	Lee M, Kim B and Kim VN: Emerging roles of RNA modification: m6A and U-tail. Cell. 158:980–987. 2014. View Article : Google Scholar
74	Flamand MN and Meyer KD: The epitranscriptome and synaptic plasticity. Curr Opin Neurobiol. 59:41–48. 2019. View Article : Google Scholar
75	Maden BE: The numerous modified nucleotides in eukaryotic ribosomal RNA. Prog Nucleic Acid Res Mol Biol. 39:241–303. 1990. View Article : Google Scholar
76	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
77	Zhang X and Jia GF: RNA epigenetic modification: N6-methyladenosine. Yi Chuan. 38:275–288. 2016.
78	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
79	Niu Y, Zhao X, Wu YS, Li MM, Wang XJ and Yang YG: N6-methyl-adenosine (m6A) in RNA: An old modification with a novel epigenetic function. Genomics Proteomics Bioinformatics. 11:8–17. 2013. View Article : Google Scholar
80	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
81	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. 485:201–206. 2012. View Article : Google Scholar
82	Chen K, Lu Z, Wang X, Fu Y, Luo GZ, Liu N, Han D, Dominissini D, Dai Q, Pan T and He C: High-resolution N(6)-methyladenosine (m(6) A) map using photo-crosslinking-assisted m(6) A sequencing. Angew Chemie Int Ed. 54:1587–1590. 2015. View Article : Google Scholar
83	Linder B, Grozhik AV, Olarerin-George AO, Meydan C, Mason CE and Jaffrey SR: Single-nucleotide-resolution mapping of m6A and m6Am throughout the transcriptome. Nat Methods. 12:767–772. 2015. View Article : Google Scholar : PubMed/NCBI
84	Roundtree IA and He C: RNA epigenetics-chemical messages for posttranscriptional gene regulation. Curr Opin Chem Biol. 30:46–51. 2016. View Article : Google Scholar
85	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
86	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 :
87	Bokar JA, Rath-Shambaugh ME, Ludwiczak R, Narayan P and 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. 269:17697–17704. 1994. View Article : Google Scholar
88	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. 8:284–296. 2014. View Article : Google Scholar : PubMed/NCBI
89	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 m 6 A residues are in the last exons, allowing the potential for 3′ UTR regulation. Genes Dev. 29:2037–2053. 2015. View Article : Google Scholar
90	Meyer KD, Patil DP, Zhou J, Zinoviev A, Skabkin MA, Elemento O, Pestova TV, Qian SB and Jaffrey SR: 5′ UTR m6A promotes cap-independent translation. Cell. 163:999–1010. 2015. View Article : Google Scholar : PubMed/NCBI
91	Zhou J, Wan J, Gao X, Zhang X, Jaffrey SR and Qian SB: Dynamic m6A mRNA methylation directs translational control of heat shock response. Nature. 526:591–594. 2015. View Article : Google Scholar : PubMed/NCBI
92	Pendleton KE, Chen B, Liu K, Hunter OV, Xie Y, Tu BP and Conrad NK: The U6 snRNA m 6 A methyltransferase METTL16 regulates SAM synthetase intron retention. Cell. 169:824–835.e14. 2017. View Article : Google Scholar
93	Dina C, Meyre D, Gallina S, Durand E, Körner A, Jacobson P, Carlsson LMS, 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
94	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
95	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 :
96	Fu Y, Jia G, Pang X, Wang RN, Wang X, Li CJ, Smemo S, Dai Q, Bailey KA, Nobrega MA, et al: FTO-mediated formation of N6-hydroxymethyladenosine and N6-formyladenosine in mammalian RNA. Nat Commun. 4:17982013. View Article : Google Scholar
97	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
98	Hess ME, Hess S, Meyer KD, Verhagen LAW, Koch L, Brönneke HS, Dietrich MO, Jordan SD, Saletore Y, Elemento O, et al: The fat mass and obesity associated gene (Fto) regulates activity of the dopaminergic midbrain circuitry. Nat Neurosci. 16:1042–1048. 2013. View Article : Google Scholar
99	Geula S, Moshitch-Moshkovitz S, Dominissini D, Mansour AA, Kol N, Salmon-Divon 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
100	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 6-methyladenosine RNA demethylase. Cancer Cell. 31:127–141. 2017. View Article : Google Scholar
101	Jaffrey SR and Kharas MG: Emerging links between m6A and misregulated mRNA methylation in cancer. Genome Med. 9:22017. View Article : Google Scholar :
102	Zhang Z, Theler D, Kaminska KH, Hiller M, de la Grange P, Pudimat R, Rafalska I, Heinrich B, Bujnicki JM, Allain FHT and Stamm S: The YTH domain is a novel RNA binding domain. J Biol Chem. 285:14701–14710. 2010. View Article : Google Scholar :
103	Xu C, Wang X, Liu K, Roundtree IA, Tempel W, Li Y, Lu Z, He C and Min J: Structural basis for selective binding of m6A RNA by the YTHDC1 YTH domain. Nat Chem Biol. 10:927–929. 2014. View Article : Google Scholar
104	Luo S and Tong L: Molecular basis for the recognition of methylated adenines in RNA by the eukaryotic YTH domain. Proc Natl Acad Sci USA. 111:13834–13839. 2014. View Article : Google Scholar
105	Zhu T, Roundtree IA, Wang P, Wang X, Wang L, Sun C, Tian Y, Li J, He C and Xu Y: Crystal structure of the YTH domain of YTHDF2 reveals mechanism for recognition of N6-methyladenosine. Cell Res. 24:1493–1496. 2014. View Article : Google Scholar : PubMed/NCBI
106	Wang X, Zhao BS, Roundtree IA, Lu Z, Han D, Ma H, Weng X, Chen K, Shi H and He C: N6-methyladenosine modulates messenger RNA translation efficiency. Cell. 161:1388–1399. 2015. View Article : Google Scholar
107	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
108	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
109	Alarcón CR, Lee H, Goodarzi H, Halberg N and Tavazoie SF: N6-methyladenosine marks primary microRNAs for processing. Nature. 519:482–485. 2015. View Article : Google Scholar : PubMed/NCBI
110	Chen T, Hao YJ, Zhang Y, Li MM, Wang M, Han W, Wu Y, Lv Y, Hao J, Wang L, et al: m6A RNA methylation is regulated by MicroRNAs and promotes reprogramming to pluripotency. Cell Stem Cell. 16:289–301. 2015. View Article : Google Scholar : PubMed/NCBI
111	Liu N, Dai Q, Zheng G, He C, Parisien M and Pan T: N6-methyladenosine-dependent RNA structural switches regulate RNA-protein interactions. Nature. 518:560–564. 2015. View Article : Google Scholar
112	Klungland A and Dahl JA: Dynamic RNA modifications in disease. Curr Opin Genet Dev. 26:47–52. 2014. View Article : Google Scholar
113	Kwok CT, Marshall AD, Rasko JEJ and Wong JJL: Erratum to: Genetic alterations of m6A regulators predict poorer survival in acute myeloid leukemia. J Hematol Oncol. 10:492017. View Article : Google Scholar :
114	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/m6A/MYC/CEBPA signaling. Cell. 172:90–105.e23. 2018. View Article : Google Scholar
115	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. View Article : Google Scholar
116	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 m6A modification. Cell Stem Cell. 22:191–205.e9. 2018. View Article : Google Scholar
117	Chhabra R: miRNA and methylation: A multifaceted liaison. Chembiochem. 16:195–203. 2015. View Article : Google Scholar
118	Hall RH: Isolation of 3-methyluridine and 3-methylcytidine from soluble ribonucleic acid. Biochem Biophys Res Commun. 12:361–364. 1963. View Article : Google Scholar
119	Xu L, Liu X, Sheng N, Oo KS, Liang J, Chionh YH, Xu J, Ye F, Gao YG, Dedon PC and Fu XY: Three distinct 3-methylcytidine (m3C) methyltransferases modify tRNA and mRNA in mice and humans. J Biol Chem. 292:14695–14703. 2017. View Article : Google Scholar :
120	Glasner H, Riml C, Micura R and Breuker K: Label-free, direct localization and relative quantitation of the RNA nucleobase methylations m6A, m5C, m3U, and m5U by top-down mass spectrometry. Nucleic Acids Res. 45:8014–8025. 2017. View Article : Google Scholar :
121	Li X, Zhu P, Ma S, Song J, Bai J, Sun F and Yi C: Chemical pulldown reveals dynamic pseudouridylation of the mammalian transcriptome. Nat Chem Biol. 11:592–597. 2015. View Article : Google Scholar
122	Charette M and Gray MW: Pseudouridine in RNA: What, where, how, and why. IUBMB Life. 49:341–351. 2000. View Article : Google Scholar : PubMed/NCBI
123	Ofengand J: Ribosomal RNA pseudouridines and pseudouridine synthases. FEBS Lett. 514:17–25. 2002. View Article : Google Scholar
124	Jack K, Bellodi C, Landry DM, Niederer RO, Meskauskas A, Musalgaonkar S, Kopmar N, Krasnykh O, Dean AM, Thompson SR, et al: rRNA pseudouridylation defects affect ribosomal ligand binding and translational fidelity from yeast to human cells. Mol Cell. 44:660–666. 2011. View Article : Google Scholar : PubMed/NCBI
125	Kiss T, Fayet-Lebaron E and Jády BE: Box H/ACA small ribonucleoproteins. Mol Cell. 37:597–606. 2010. View Article : Google Scholar
126	Yu AT, Ge J and Yu YT: Pseudouridines in spliceosomal snRNAs. Protein Cell. 2:712–725. 2011. View Article : Google Scholar : PubMed/NCBI
127	Karijolich J and Yu YT: Converting nonsense codons into sense codons by targeted pseudouridylation. Nature. 474:395–398. 2011. View Article : Google Scholar : PubMed/NCBI
128	Rosselló-Tortella M, Ferrer G and Esteller M: Epitranscriptomics in hematopoiesis and hematologic malignancies. Blood Cancer Discov. 1:26–31. 2020. View Article : Google Scholar
129	Alseth I, Dalhus B and Bjørås M: Inosine in DNA and RNA. Curr Opin Genet Dev. 26:116–123. 2014. View Article : Google Scholar : PubMed/NCBI
130	Bass BL, Nishikura K, Keller W, Seeburg PH, Emeson RB, O'Connell MA, Samuel CE and Herbert A: A standardized nomenclature for adenosine deaminases that act on RNA. RNA. 3:947–949. 1997.
131	Li X, Yang L and Chen LL: The biogenesis, functions, and challenges of circular RNAs. Mol Cell. 71:428–442. 2018. View Article : Google Scholar
132	Legnini I, Di Timoteo G, Rossi F, Morlando M, Briganti F, Sthandier O, Fatica A, Santini T, Andronache A, Wade M, et al: Circ-ZNF609 is a circular rna that can be translated and functions in myogenesis. Mol Cell. 66:22–37.e9. 2017. View Article : Google Scholar : PubMed/NCBI
133	Pamudurti NR, Bartok O, Jens M, Ashwal-Fluss R, Stottmeister C, Ruhe L, Hanan M, Wyler E, Perez-Hernandez D, Ramberger E, et al: Translation of CircRNAs. Mol Cell. 66:9–21.e7. 2017. View Article : Google Scholar :
134	Haimov O, Sinvani H and Dikstein R: Cap-dependent, scanning-free translation initiation mechanisms. Biochim Biophys Acta. 1849:1313–1318. 2015. View Article : Google Scholar : PubMed/NCBI
135	Yang Y, Gao X, Zhang M, Yan S, Sun C, Xiao F, Huang N, Yang X, Zhao K, Zhou H, et al: Novel role of FBXW7 Circular RNA in repressing glioma tumorigenesis. J Natl Cancer Inst. 110:304–315. 2018. View Article : Google Scholar :
136	Zhang M, Huang N, Yang X, Luo J, Yan S, Xiao F, Chen W, Gao X, Zhao K, Zhou H, et al: A novel protein encoded by the circular form of the SHPRH gene suppresses glioma tumorigenesis. Oncogene. 37:1805–1814. 2018. View Article : Google Scholar : PubMed/NCBI
137	Liang WC, Wong CW, Liang PP, Shi M, Cao Y, Rao ST, Tsui SKW, Waye MMY, Zhang Q, Fu WM and Zhang JF: Translation of the circular RNA circβ-catenin promotes liver cancer cell growth through activation of the wnt pathway. Genome Biol. 20:842019. View Article : Google Scholar
138	Huang X, He M, Huang S, Lin R, Zhan M, Yang D, Shen H, Xu S, Cheng W, Yu J, et al: Circular RNA circERBB2 promotes gallbladder cancer progression by regulating PA2G4-dependent rDNA transcription. Mol Cancer. 18:1662019. View Article : Google Scholar
139	Chen RX, Chen X, Xia LP, Zhang JX, Pan ZZ, Ma XD, Han K, Chen JW, Judde JG, Deas O, et al: 6-methyladenosine modification of circNSUN2 facilitates cytoplasmic export and stabilizes HMGA2 to promote colorectal liver metastasis. Nat Commun. 10:46952019. View Article : Google Scholar
140	Wu P, Fang X, Liu Y, Tang Y, Wang W, Li X and Fan Y: N6-methyladenosine modification of circCUX1 confers radio-resistance of hypopharyngeal squamous cell carcinoma through caspase1 pathway. Cell Death Dis. 12:2982021. View Article : Google Scholar
141	Park OH, Ha H, Lee Y, Boo SH, Kwon DH, Song HK and Kim YK: Endoribonucleolytic cleavage of m6A-containing RNAs by RNase P/MRP complex. Mol Cell. 74:494–507.e8. 2019. View Article : Google Scholar
142	Zhang L, Hou C, Chen C, Guo Y, Yuan W, Yin D, Liu J and Sun Z: The role of N6-methyladenosine (m6A) modification in the regulation of circRNAs. Mol Cancer. 19:1052020. View Article : Google Scholar
143	Chen YG, Chen R, Ahmad S, Verma R, Kasturi SP, Amaya L, Broughton JP, Kim J, Cadena C, Pulendran B, et al: N6-methyladenosine modification controls circular RNA immunity. Mol Cell. 76:96–109.e9. 2019. View Article : Google Scholar
144	Lux S, Blätte TJ, Gillissen B, Richter A, Cocciardi S, Skambraks S, Schwarz K, Schrezenmeier H, Döhner H, Döhner K, et al: Deregulated expression of circular RNAs in acute myeloid leukemia. Blood Adv. 5:1490–1503. 2021. View Article : Google Scholar : PubMed/NCBI
145	Bell CC, Fennell KA, Chan YC, Rambow F, Yeung MM, Vassiliadis D, Lara L, Yeh P, Martelotto LG, Rogiers A, et al: Targeting enhancer switching overcomes non-genetic drug resistance in acute myeloid leukaemia. Nat Commun. 10:27232019. View Article : Google Scholar :
146	Arteaga CL and Engelman JA: ERBB receptors: From oncogene discovery to basic science to mechanism-based cancer therapeutics. Cancer Cell. 25:282–303. 2014. View Article : Google Scholar :
147	Conn SJ, Pillman KA, Toubia J, Conn VM, Salmanidis M, Phillips CA, Roslan S, Schreiber AW, Gregory PA and Goodall GJ: The RNA binding protein quaking regulates formation of circRNAs. Cell. 160:1125–1134. 2015. View Article : Google Scholar
148	L'Abbate A, Tolomeo D, Cifola I, Severgnini M, Turchiano A, Augello B, Squeo G, D'Addabbo P, Traversa D, Daniele G, et al: MYC-containing amplicons in acute myeloid leukemia: Genomic structures, evolution, and transcriptional consequences. Leukemia. 32:2152–2166. 2018. View Article : Google Scholar
149	Guarnerio J, Bezzi M, Jeong JC, Paffenholz SV, Berry K, Naldini MM, Lo-Coco F, Tay Y, Beck AH and Pandolfi PP: Oncogenic role of fusion-circRNAs derived from cancer-associated chromosomal translocations. Cell. 165:289–302. 2016. View Article : Google Scholar
150	Wu DM, Wen X, Han XR, Wang S, Wang YJ, Shen M, Fan SH, Zhang ZF, Shan Q, Li MQ, et al: Role of circular RNA DLEU2 in human acute myeloid leukemia. Mol Cell Biol. 38:e00259–e00218. 2018. View Article : Google Scholar : PubMed/NCBI
151	Ping L, Jian-Jun C, Chu-Shu L, Guang-Hua L and Ming Z: Silencing of circ_0009910 inhibits acute myeloid leukemia cell growth through increasing miR-20a-5p. Blood Cells Mol Dis. 75:41–47. 2019. View Article : Google Scholar
152	Fan H, Li Y, Liu C, Liu Y, Bai J and Li W: Circular RNA-100290 promotes cell proliferation and inhibits apoptosis in acute myeloid leukemia cells via sponging miR-203. Biochem Biophys Res Commun. 507:178–184. 2018. View Article : Google Scholar : PubMed/NCBI
153	Chen H, Liu T, Liu J, Feng Y, Wang B, Wang J, Bai J, Zhao W, Shen Y, Wang X, et al: Circ-ANAPC7 is upregulated in acute myeloid leukemia and appears to target the miR-181 family. Cell Physiol Biochem. 47:1998–2007. 2018. View Article : Google Scholar : PubMed/NCBI
154	Li W, Zhong C, Jiao J, Li P, Cui B, Ji C and Ma D: Characterization of hsa_circ_0004277 as a new biomarker for acute myeloid leukemia via circular RNA profile and bioinformatics analysis. Int J Mol Sci. 18:5972017. View Article : Google Scholar :
155	Shang J, Chen WM, Wang ZH, Wei TN, Chen ZZ and Wu WB: CircPAN3 mediates drug resistance in acute myeloid leukemia through the miR-153-5p/miR-183-5p-XIAP axis. Exp Hematol. 70:42–54.e3. 2019. View Article : Google Scholar
156	Hirsch S, Blätte TJ, Grasedieck S, Cocciardi S, Rouhi A, Jongen-Lavrencic M, Paschka P, Krönke J, Gaidzik VI, Döhner H, et al: Circular RNAs of the nucleophosmin (NPM1) gene in acute myeloid leukemia. Haematologica. 102:2039–2047. 2017. View Article : Google Scholar : PubMed/NCBI
157	Chen LL: The biogenesis and emerging roles of circular RNAs. Nat Rev Mol Cell Biol. 17:205–211. 2016. View Article : Google Scholar
158	Okcanoğlu TB and Gündüz C: Circular RNAs in leukemia (Review). Biomed Rep. 10:87–91. 2019.
159	Qu S, Yang X, Li X, Wang J, Gao Y, Shang R, Sun W, Dou K and Li H: Circular RNA: A new star of noncoding RNAs. Cancer Lett. 365:141–148. 2015. View Article : Google Scholar : PubMed/NCBI
160	Dudekula DB, Panda AC, Grammatikakis I, De S, Abdelmohsen K and Gorospe M: CircInteractome: A web tool for exploring circular RNAs and their interacting proteins and microRNAs. RNA Biol. 13:34–42. 2016. View Article : Google Scholar
161	Wang E, Lu SX, Pastore A, Chen X, Imig J, Lee SC, Hockemeyer K, Ghebrechristos YE, Yoshimi A, Inoue D, et al: Targeting an RNA-binding protein network in acute myeloid leukemia. Cancer Cell. 35:369–384.e7. 2019. View Article : Google Scholar
162	Yoshida K, Sanada M, Shiraishi Y, Nowak D, Nagata Y, Yamamoto R, Sato Y, Sato-Otsubo A, Kon A, Nagasaki M, et al: Frequent pathway mutations of splicing machinery in myelodysplasia. Nature. 478:64–69. 2011. View Article : Google Scholar : PubMed/NCBI
163	Sun YM, Wang WT, Zeng ZC, Chen TQ, Han C, Pan Q, Huang W, Fang K, Sun LY, Zhou YF, et al: circMYBL2, a circRNA from MYBL2, regulates FLT3 translation by recruiting PTBP1 to promote FLT3-ITD AML progression. Blood. 134:1533–1546. 2019. View Article : Google Scholar
164	Guil S and Esteller M: Cis-acting noncoding RNAs: Friends and foes. Nat Struct Mol Biol. 19:1068–1075. 2012. View Article : Google Scholar : PubMed/NCBI
165	Mercer TR and Mattick JS: Structure and function of long noncoding RNAs in epigenetic regulation. Nat Struct Mol Biol. 20:300–307. 2013. View Article : Google Scholar
166	Conn VM, Hugouvieux V, Nayak A, Conos SA, Capovilla G, Cildir G, Jourdain A, Tergaonkar V, Schmid M, Zubieta C and Conn SJ: A circRNA from SEPALLATA3 regulates splicing of its cognate mRNA through R-loop formation. Nat Plants. 3:170532017. View Article : Google Scholar : PubMed/NCBI
167	Schmitz KM, Mayer C, Postepska A and Grummt I: Interaction of noncoding RNA with the rDNA promoter mediates recruitment of DNMT3b and silencing of rRNA genes. Genes Dev. 24:2264–2269. 2010. View Article : Google Scholar : PubMed/NCBI
168	Starke S, Jost I, Rossbach O, Schneider T, Schreiner S, Hung LH and Bindereif A: Exon circularization requires canonical splice signals. Cell Rep. 10:103–111. 2015. View Article : Google Scholar
169	van Rossum D, Verheijen BM and Pasterkamp RJ: Circular RNAs: Novel regulators of neuronal development. Front Mol Neurosci. 9:742016. View Article : Google Scholar : PubMed/NCBI
170	Chen C, Yuan W, Zhou Q, Shao B, Guo Y, Wang W, Yang S, Guo Y, Zhao L, Dang Q, et al: N6-methyladenosine-induced circ1662 promotes metastasis of colorectal cancer by accelerating YAP1 nuclear localization. Theranostics. 11:4298–4315. 2021. View Article : Google Scholar
171	Dai F, Wu Y, Lu Y, An C, Zheng X, Dai L, Guo Y, Zhang L, Li H, Xu W and Gao W: Crosstalk between RNA m6A modification and non-coding RNA contributes to cancer growth and progression. Mol Ther Nucleic Acids. 22:62–71. 2020. View Article : Google Scholar
172	Harding CV, Heuser JE and Stahl PD: Exosomes: Looking back three decades and into the future. J Cell Biol. 200:367–371. 2013. View Article : Google Scholar : PubMed/NCBI
173	Melo SA, Sugimoto H, O'Connell JT, Kato N, Villanueva A, Vidal A, Qiu L, Vitkin E, Perelman LT, Melo CA, et al: Cancer exosomes perform cell-independent MicroRNA biogenesis and promote tumorigenesis. Cancer Cell. 26:707–721. 2014. View Article : Google Scholar :
174	Boyiadzis M and Whiteside TL: Exosomes in acute myeloid leukemia inhibit hematopoiesis. Curr Opin Hematol. 25:279–284. 2018. View Article : Google Scholar