Regulations of m<sup>6</sup>A and other RNA modifications and their roles in cancer

doi:10.1007/s11684-024-1064-8

Front. Med.

2024, Vol. 18

Issue (4) : 622-648 https://doi.org/10.1007/s11684-024-1064-8

Regulations of m⁶A and other RNA modifications and their roles in cancer

Xin-Hui Chen, Kun-Xiong Guo, Jing Li, Shu-Hui Xu, Huifang Zhu, Guang-Rong Yan(

)

Biomedicine Research Center, Guangdong Provincial Key Laboratory of Major Obstetric Disease, Guangdong Provincial Clinical Research Center for Obstetrics and Gynecology, State Key Laboratory of Respiratory Disease, the Third Affiliated Hospital of Guangzhou Medical University, Guangzhou 510150, China

Download: PDF(4517 KB) HTML
Export: BibTeX | EndNote | Reference Manager | ProCite | RefWorks

Abstract

RNA modification is an essential component of the epitranscriptome, regulating RNA metabolism and cellular functions. Several types of RNA modiﬁcations have been identified to date; they include N⁶-methyladenosine (m⁶A), N¹-methyladenosine (m¹A), 5-methylcytosine (m⁵C), N⁷-methylguanosine (m⁷G), N⁶,2′-O-dimethyladenosine (m⁶A_m), N⁴-acetylcytidine (ac⁴C), etc. RNA modifications, mediated by regulators including writers, erasers, and readers, are associated with carcinogenesis, tumor microenvironment, metabolic reprogramming, immunosuppression, immunotherapy, chemotherapy, etc. A novel perspective indicates that regulatory subunits and post-translational modifications (PTMs) are involved in the regulation of writer, eraser, and reader functions in mediating RNA modifications, tumorigenesis, and anticancer therapy. In this review, we summarize the advances made in the knowledge of different RNA modifications (especially m⁶A) and focus on RNA modification regulators with functions modulated by a series of factors in cancer, including regulatory subunits (proteins, noncoding RNA or peptides encoded by long noncoding RNA) and PTMs (acetylation, SUMOylation, lactylation, phosphorylation, etc.). We also delineate the relationship between RNA modification regulator functions and carcinogenesis or cancer progression. Additionally, inhibitors that target RNA modification regulators for anticancer therapy and their synergistic effect combined with immunotherapy or chemotherapy are discussed.

Keywords RNA modification writers erasers readers regulatory subunits PTMs cancer

Corresponding Author(s): Guang-Rong Yan

Just Accepted Date: 29 April 2024 Online First Date: 21 June 2024 Issue Date: 30 August 2024

Cite this article:

Xin-Hui Chen,Kun-Xiong Guo,Jing Li, et al. Regulations of m⁶A and other RNA modifications and their roles in cancer[J]. Front. Med., 2024, 18(4): 622-648.

URL:

https://academic.hep.com.cn/fmd/EN/10.1007/s11684-024-1064-8
https://academic.hep.com.cn/fmd/EN/Y2024/V18/I4/622

Fig.1 Schematic representation of m⁶A regulators and their regulatory subunits and post-translational modifications in cancer. Dysregulation of m⁶A regulators (writers, erasers, and readers) influences the metabolism of target RNAs and cellular function, ultimately contributing to carcinogenesis and cancer progression. Among m⁶A regulators, reader proteins specifically recognize and selectively bind to m⁶A sites, modulating the fates of the target RNAs in an m⁶A-dependent manner, thereby functioning as the bridge between the m⁶A modification and cancer. Notably, m⁶A modification regulators can be modulated by their regulatory subunits (proteins, ncRNAs or peptides encoded by lncRNAs) or PTMs, which affect their biological functions in cancer. (The graphics was created with BioRender.com.)

Fig.2 Regulatory subunits of m⁶A regulators. The figure shows the major regulatory subunits of RNA m⁶A writers, erasers, and readers, as well as the biological functions of these regulatory subunits. METTL3, METTL14, and WTAP form the core component of the m⁶A methyltransferase complex. As reported, eIF3h interacts with METTL3, which promotes mRNA circularization and translation. PIN1 prevents ubiquitin-dependent proteasomal and lysosomal degradation of METTL3. In addition, TRMT112 stabilizes another m⁶A methyltransferase, METTL5, which is responsible for m⁶A methylation on 18S rRNA. PSPC1 or RBM33/SENP1 facilitates the recognition ability or demethylase activity of the m⁶A demethylase ALKBH5 on mRNA, respectively. SFPQ leads to the demethylation of mRNA m⁶A through recruiting FTO to these specific mRNA sites. The binding of FBW7 induces proteasomal degradation of YTHDF2. Furthermore, lncRNA CBSLR and lncRNA STEAP3-AS1 are involved in the binding of YTHDF2 with the m⁶A-modified coding sequence of mRNA. RBRP, circEZH2 or the lncRNA DMDRMR regulates the m⁶A recognition ability, degradation or RNA binding capacity of the m⁶A reader proteins IGF2BP1-3, respectively. (The graphics was created with BioRender.com.)

Fig.3 Processes and biological functions of three different post-translational modifications of ALKBH5. (A) ALKBH5 is acetylated by KAT8 and deacetylated by HDAC7. The RNA binding protein PSPC1 preferentially interacts with acetylated ALKBH5 but not nonacetylated ALKBH5 and is involved in the recognition of m⁶A on mRNAs by ALKBH5, ultimately promoting the removal of m⁶A marks. (B) PIAS4-mediated SUMOylation of ALKBH5. RBM33 interacts with SENP1 and recruits ALKBH5 to m⁶A sites. Subsequently, SENP1 removes a SUMO group from ALKBH5 and thus promotes its demethylase activity. (C) ROS/ERK/JNK signaling results in the phosphorylation of ALKBH5. Phosphorylation of ALKBH5 facilitates its subsequent SUMOylation, hereby downregulating its m⁶A demethylase activity by blocking substrate accessibility. (The graphics was created with BioRender.com.)

Fig.4 Different post-translational modifications of METTL3. The RNA m⁶A methyltransferase activity of METTL3 is regulated by its post-translational modifications (SUMOylation, acetylation, ubiquitination, phosphorylation, and lactylation). (The graphics was created with BioRender.com.)

Fig.5 Processes and biological functions of three different post-translational modifications of YTHDF2. (A) YTHDF2 K571 SUMOylation significantly enhances its affinity for m⁶A-modified mRNAs. (B) YTHDF2 S39 and T381 phosphorylation enhances the stability of YTHDF2, subsequently facilitating the degradation of mRNAs in an m⁶A-dependent manner. (C) O-GlcNAcylation of YTHDF2 at S263 leads to increased stability of YTHDF2 by inhibiting its ubiquitination. (The graphics was created with BioRender.com.)

Tab.1 Inhibitors targeting m⁶A-related regulators

Tab.2 Synergistic therapy based on inhibitors of m⁶A regulators

Fig.6 Regulatory subunits and PTMs of m⁵C, m⁷G, and ac⁴C regulators. (A) SUMOylation of the m⁵C methyltransferase NSUN2 enhances the stability of NSUN2, thereby increasing the abundance of m⁵C marks on mRNAs. (B) Phosphorylation of the m⁷G methyltransferase RNMT increases its m⁷G-cap methyltransferase activity and promotes the production of proteins. (C) PML, a regulatory subunit of the m⁷G reader protein elF4E, directly interacts with elF4E to attenuate the affinity of elF4E for the m⁷G cap. (D) The phosphorylation of the m⁷G reader protein eIF4E enhances its binding ability to the m⁷G cap in many mRNAs, subsequently facilitating their translation. (E) The 2-hydroxyisobutyrylation (Khib) modification of the ac⁴C acetyltransferase NAT10 enhances its interaction with the deubiquitinase USP39, thereby increasing the stability of NAT10 and ac⁴C marks on mRNAs. (The graphics was created with BioRender.com.)

Tab.3 The writers, erasers, and readers of m¹A, m⁵C, m⁷G, m⁶A_m, and ac⁴C and their functions, regulatory subunits, and PTMs

Tab.4 Inhibitors targeting other RNA modification regulators

1	H Sung, J Ferlay, RL Siegel, M Laversanne, I Soerjomataram, A Jemal, F Bray. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2021; 71(3): 209–249 https://doi.org/10.3322/caac.21660
2	SJ Vervoort, JR Devlin, N Kwiatkowski, M Teng, NS Gray, RW Johnstone. Targeting transcription cycles in cancer. Nat Rev Cancer 2022; 22(1): 5–24 https://doi.org/10.1038/s41568-021-00411-8
3	D Wiener, S Schwartz. The epitranscriptome beyond m6A. Nat Rev Genet 2021; 22(2): 119–131 https://doi.org/10.1038/s41576-020-00295-8
4	I Barbieri, T Kouzarides. Role of RNA modifications in cancer. Nat Rev Cancer 2020; 20(6): 303–322 https://doi.org/10.1038/s41568-020-0253-2
5	Y Gu, S Niu, Y Wang, L Duan, Y Pan, Z Tong, X Zhang, Z Yang, B Peng, X Wang, X Han, Y Li, T Cheng, Y Liu, L Shang, T Liu, X Yang, M Sun, S Jiang, C Zhang, N Zhang, Q Ye, S Gao. DMDRMR-mediated regulation of m6A-modified CDK4 by m6A reader IGF2BP3 drives ccRCC progression. Cancer Res 2021; 81(4): 923–934 https://doi.org/10.1158/0008-5472.CAN-20-1619
6	S Zhu, JZ Wang, D Chen, YT He, N Meng, M Chen, RX Lu, XH Chen, XL Zhang, GR Yan. An oncopeptide regulates m6A recognition by the m6A reader IGF2BP1 and tumorigenesis. Nat Commun 2020; 11(1): 1685 https://doi.org/10.1038/s41467-020-15403-9
7	XL Zhang, XH Chen, B Xu, M Chen, S Zhu, N Meng, JZ Wang, H Zhu, D Chen, JB Liu, GR Yan. K235 acetylation couples with PSPC1 to regulate the m6A demethylation activity of ALKBH5 and tumorigenesis. Nat Commun 2023; 14(1): 3815 https://doi.org/10.1038/s41467-023-39414-4
8	L Liao, Y He, SJ Li, XM Yu, ZC Liu, YY Liang, H Yang, J Yang, GG Zhang, CM Deng, X Wei, YD Zhu, TY Xu, CC Zheng, C Cheng, A Li, ZG Li, JB Liu, B Li. Lysine 2-hydroxyisobutyrylation of NAT10 promotes cancer metastasis in an ac4C-dependent manner. Cell Res 2023; 33(5): 355–371 https://doi.org/10.1038/s41422-023-00793-4
9	X Deng, Y Qing, D Horne, H Huang, J Chen. The roles and implications of RNA m6A modification in cancer. Nat Rev Clin Oncol 2023; 20(8): 507–526 https://doi.org/10.1038/s41571-023-00774-x
10	H Huang, H Weng, J Chen. m6A modification in coding and non-coding RNAs: roles and therapeutic implications in cancer. Cancer Cell 2020; 37(3): 270–288 https://doi.org/10.1016/j.ccell.2020.02.004
11	P Śledź, M Jinek. Structural insights into the molecular mechanism of the m6A writer complex. eLife 2016; 5: e18434 https://doi.org/10.7554/eLife.18434
12	X Wang, J Feng, Y Xue, Z Guan, D Zhang, Z Liu, Z Gong, Q Wang, J Huang, C Tang, T Zou, P Yin. Structural basis of N6-adenosine methylation by the METTL3-METTL14 complex. Nature 2016; 534(7608): 575–578 https://doi.org/10.1038/nature18298
13	CM Wei, A Gershowitz, B Moss. Methylated nucleotides block 5′ terminus of HeLa cell messenger RNA. Cell 1975; 4(4): 379–386 https://doi.org/10.1016/0092-8674(75)90158-0
14	K Boulias, EL Greer. Biological roles of adenine methylation in RNA. Nat Rev Genet 2023; 24(3): 143–160 https://doi.org/10.1038/s41576-022-00534-0
15	M Li, X Zha, S Wang. The role of N6-methyladenosine mRNA in the tumor microenvironment. Biochim Biophys Acta Rev Cancer 2021; 1875(2): 188522 https://doi.org/10.1016/j.bbcan.2021.188522
16	KA Doxtader, P Wang, AM Scarborough, D Seo, NK Conrad, Y Nam. Structural basis for regulation of METTL16, an S-adenosylmethionine homeostasis factor. Mol Cell 2018; 71(6): 1001–1011.e4 https://doi.org/10.1016/j.molcel.2018.07.025
17	J Liu, Y Yue, D Han, X Wang, Y Fu, L Zhang, G Jia, M Yu, Z Lu, X Deng, Q Dai, W Chen, C He. A METTL3-METTL14 complex mediates mammalian nuclear RNA N6-adenosine methylation. Nat Chem Biol 2014; 10(2): 93–95 https://doi.org/10.1038/nchembio.1432
18	P Wang, KA Doxtader, Y Nam. Structural basis for cooperative function of Mettl3 and Mettl14 methyltransferases. Mol Cell 2016; 63(2): 306–317 https://doi.org/10.1016/j.molcel.2016.05.041
19	DP Patil, CK Chen, BF Pickering, A Chow, C Jackson, M Guttman, SR Jaffrey. m6A RNA methylation promotes XIST-mediated transcriptional repression. Nature 2016; 537(7620): 369–373 https://doi.org/10.1038/nature19342
20	J Wen, R Lv, H Ma, H Shen, C He, J Wang, F Jiao, H Liu, P Yang, L Tan, F Lan, YG Shi, C He, Y Shi, J Diao. Zc3h13 regulates nuclear RNA m6A methylation and mouse embryonic stem cell self-renewal. Mol Cell 2018; 69(6): 1028–1038.e6 https://doi.org/10.1016/j.molcel.2018.02.015
21	Y Yue, J Liu, X Cui, J Cao, G Luo, Z Zhang, T Cheng, M Gao, X Shu, H Ma, F Wang, X Wang, B Shen, Y Wang, X Feng, C He, J Liu. VIRMA mediates preferential m6A mRNA methylation in 3′UTR and near stop codon and associates with alternative polyadenylation. Cell Discov 2018; 4: 10 https://doi.org/10.1038/s41421-018-0019-0
22	P Bawankar, T Lence, C Paolantoni, IU Haussmann, M Kazlauskiene, D Jacob, JB Heidelberger, FM Richter, MP Nallasivan, V Morin, N Kreim, P Beli, M Helm, M Jinek, M Soller, JY Roignant. Hakai is required for stabilization of core components of the m6A mRNA methylation machinery. Nat Commun 2021; 12(1): 3778 https://doi.org/10.1038/s41467-021-23892-5
23	N van Tran, FGM Ernst, BR Hawley, C Zorbas, N Ulryck, P Hackert, KE Bohnsack, MT Bohnsack, SR Jaffrey, M Graille, DLJ Lafontaine. The human 18S rRNA m6A methyltransferase METTL5 is stabilized by TRMT112. Nucleic Acids Res 2019; 47(15): 7719–7733 https://doi.org/10.1093/nar/gkz619
24	KE Pendleton, B Chen, K Liu, OV Hunter, Y Xie, BP Tu, NK Conrad. The U6 snRNA m6A methyltransferase METTL16 regulates SAM synthetase intron retention. Cell 2017; 169(5): 824–835.e14 https://doi.org/10.1016/j.cell.2017.05.003
25	H Ma, X Wang, J Cai, Q Dai, SK Natchiar, R Lv, K Chen, Z Lu, H Chen, YG Shi, F Lan, J Fan, BP Klaholz, T Pan, Y Shi, C He. N6-methyladenosine methyltransferase ZCCHC4 mediates ribosomal RNA methylation. Nat Chem Biol 2019; 15(1): 88–94 https://doi.org/10.1038/s41589-018-0184-3
26	G Jia, Y Fu, X Zhao, Q Dai, G Zheng, Y Yang, C Yi, T Lindahl, T Pan, YG Yang, C He. N6-methyladenosine in nuclear RNA is a major substrate of the obesity-associated FTO. Nat Chem Biol 2011; 7(12): 885–887 https://doi.org/10.1038/nchembio.687
27	G Zheng, JA Dahl, Y Niu, P Fedorcsak, CM Huang, CJ Li, CB Vågbø, Y Shi, WL Wang, SH Song, Z Lu, RP Bosmans, Q Dai, YJ Hao, X Yang, WM Zhao, WM Tong, XJ Wang, F Bogdan, K Furu, Y Fu, G Jia, X Zhao, J Liu, HE Krokan, A Klungland, YG Yang, C He. ALKBH5 is a mammalian RNA demethylase that impacts RNA metabolism and mouse fertility. Mol Cell 2013; 49(1): 18–29 https://doi.org/10.1016/j.molcel.2012.10.015
28	BS Zhao, IA Roundtree, C He. Post-transcriptional gene regulation by mRNA modifications. Nat Rev Mol Cell Biol 2017; 18(1): 31–42 https://doi.org/10.1038/nrm.2016.132
29	X Wang, Z Lu, A Gomez, GC Hon, Y Yue, D Han, Y Fu, M Parisien, Q Dai, G Jia, B Ren, T Pan, C He. N6-methyladenosine-dependent regulation of messenger RNA stability. Nature 2014; 505(7481): 117–120 https://doi.org/10.1038/nature12730
30	D Dominissini, S Moshitch-Moshkovitz, S Schwartz, M Salmon-Divon, L Ungar, S Osenberg, K Cesarkas, J Jacob-Hirsch, N Amariglio, M Kupiec, R Sorek, G Rechavi. Topology of the human and mouse m6A RNA methylomes revealed by m6A-seq. Nature 2012; 485(7397): 201–206 https://doi.org/10.1038/nature11112
31	H Huang, H Weng, W Sun, X Qin, H Shi, H Wu, BS Zhao, A Mesquita, C Liu, CL Yuan, YC Hu, S Hüttelmaier, JR Skibbe, R Su, X Deng, L Dong, M Sun, C Li, S Nachtergaele, Y Wang, C Hu, K Ferchen, KD Greis, X Jiang, M Wei, L Qu, JL Guan, C He, J Yang, J Chen. Recognition of RNA N6-methyladenosine by IGF2BP proteins enhances mRNA stability and translation. Nat Cell Biol 2018; 20(3): 285–295 https://doi.org/10.1038/s41556-018-0045-z
32	KD Meyer, DP Patil, J Zhou, A Zinoviev, MA Skabkin, O Elemento, TV Pestova, SB Qian, SR Jaffrey. 5′ UTR m6A promotes cap-independent translation. Cell 2015; 163(4): 999–1010 https://doi.org/10.1016/j.cell.2015.10.012
33	BM Edens, C Vissers, J Su, S Arumugam, Z Xu, H Shi, N Miller, F Rojas Ringeling, GL Ming, C He, H Song, YC Ma. FMRP modulates neural differentiation through m6A-dependent mRNA nuclear export. Cell Rep 2019; 28(4): 845–854.e5 https://doi.org/10.1016/j.celrep.2019.06.072
34	R Wu, A Li, B Sun, JG Sun, J Zhang, T Zhang, Y Chen, Y Xiao, Y Gao, Q Zhang, J Ma, X Yang, Y Liao, WY Lai, X Qi, S Wang, Y Shu, HL Wang, F Wang, YG Yang, Z Yuan. A novel m6A reader Prrc2a controls oligodendroglial specification and myelination. Cell Res 2019; 29(1): 23–41 https://doi.org/10.1038/s41422-018-0113-8
35	N Liu, Q Dai, G Zheng, C He, M Parisien, T Pan. N6-methyladenosine-dependent RNA structural switches regulate RNA-protein interactions. Nature 2015; 518(7540): 560–564 https://doi.org/10.1038/nature14234
36	KI Zhou, H Shi, R Lyu, AC Wylder, Ż Matuszek, JN Pan, C He, M Parisien, T Pan. Regulation of co-transcriptional pre-mRNA splicing by m6A through the low-complexity protein hnRNPG. Mol Cell 2019; 76(1): 70–81.e9 https://doi.org/10.1016/j.molcel.2019.07.005
37	N Liu, KI Zhou, M Parisien, Q Dai, L Diatchenko, T Pan. N6-methyladenosine alters RNA structure to regulate binding of a low-complexity protein. Nucleic Acids Res 2017; 45(10): 6051–6063 https://doi.org/10.1093/nar/gkx141
38	X Wang, BS Zhao, IA Roundtree, Z Lu, D Han, H Ma, X Weng, K Chen, H Shi, C He. N6-methyladenosine modulates messenger RNA translation efficiency. Cell 2015; 161(6): 1388–1399 https://doi.org/10.1016/j.cell.2015.05.014
39	J Tong, RA Flavell, HB Li. RNA m6A modification and its function in diseases. Front Med 2018; 12(4): 481–489 https://doi.org/10.1007/s11684-018-0654-8
40	KD Meyer, SR Jaffrey. Rethinking m6A readers, writers, and erasers. Annu Rev Cell Dev Biol 2017; 6; 33: 319–342 https://doi.org/10.1146/annurev-cellbio-100616-060758
41	H Du, Y Zhao, J He, Y Zhang, H Xi, M Liu, J Ma, L Wu. YTHDF2 destabilizes m6A-containing RNA through direct recruitment of the CCR4-NOT deadenylase complex. Nat Commun 2016; 7: 12626 https://doi.org/10.1038/ncomms12626
42	H Shi, X Wang, Z Lu, BS Zhao, H Ma, PJ Hsu, C Liu, C He. YTHDF3 facilitates translation and decay of N6-methyladenosine-modified RNA. Cell Res 2017; 27(3): 315–328 https://doi.org/10.1038/cr.2017.15
43	S Zaccara, SR Jaffrey. A unified model for the function of YTHDF proteins in regulating m6A-modified mRNA. Cell 2020; 181(7): 1582–1595.e18 https://doi.org/10.1016/j.cell.2020.05.012
44	Z Zou, C Sepich-Poore, X Zhou, J Wei, C He. The mechanism underlying redundant functions of the YTHDF proteins. Genome Biol 2023; 24(1): 17 https://doi.org/10.1186/s13059-023-02862-8
45	H Shima, M Matsumoto, Y Ishigami, M Ebina, A Muto, Y Sato, S Kumagai, K Ochiai, T Suzuki, K Igarashi. S-adenosylmethionine synthesis is regulated by selective N6-adenosine methylation and mRNA degradation involving METTL16 and YTHDC1. Cell Rep 2017; 21(12): 3354–3363 https://doi.org/10.1016/j.celrep.2017.11.092
46	Y Mao, L Dong, XM Liu, J Guo, H Ma, B Shen, SB Qian. m6A in mRNA coding regions promotes translation via the RNA helicase-containing YTHDC2. Nat Commun 2019; 10(1): 5332 https://doi.org/10.1038/s41467-019-13317-9
47	PJ Hsu, Y Zhu, H Ma, Y Guo, X Shi, Y Liu, M Qi, Z Lu, H Shi, J Wang, Y Cheng, G Luo, Q Dai, M Liu, X Guo, J Sha, B Shen, C He. Ythdc2 is an N6-methyladenosine binding protein that regulates mammalian spermatogenesis. Cell Res 2017; 27(9): 1115–1127 https://doi.org/10.1038/cr.2017.99
48	J Kretschmer, H Rao, P Hackert, KE Sloan, C Höbartner, MT Bohnsack. The m6A reader protein YTHDC2 interacts with the small ribosomal subunit and the 5′-3′ exoribonuclease XRN1. RNA 2018; 24(10): 1339–1350 https://doi.org/10.1261/rna.064238.117
49	M Hafner, M Landthaler, L Burger, M Khorshid, J Hausser, P Berninger, A Rothballer, M Jr Ascano, AC Jungkamp, M Munschauer, A Ulrich, GS Wardle, S Dewell, M Zavolan, T Tuschl. Transcriptome-wide identification of RNA-binding protein and microRNA target sites by PAR-CLIP. Cell 2010; 141(1): 129–141 https://doi.org/10.1016/j.cell.2010.03.009
50	W Xiao, S Adhikari, U Dahal, YS Chen, YJ Hao, BF Sun, HY Sun, A Li, XL Ping, WY Lai, X Wang, HL Ma, CM Huang, Y Yang, N Huang, GB Jiang, HL Wang, Q Zhou, XJ Wang, YL Zhao, YG Yang. Nuclear m6A reader YTHDC1 regulates mRNA splicing. Mol Cell 2016; 61(4): 507–519 https://doi.org/10.1016/j.molcel.2016.01.012
51	IA Roundtree, GZ Luo, Z Zhang, X Wang, T Zhou, Y Cui, J Sha, X Huang, L Guerrero, P Xie, E He, B Shen, C He. YTHDC1 mediates nuclear export of N6-methyladenosine methylated mRNAs. eLife 2017; 6: e31311 https://doi.org/10.7554/eLife.31311
52	OH Park, H Ha, Y Lee, SH Boo, DH Kwon, HK Song, YK Kim. Endoribonucleolytic cleavage of m6A-containing RNAs by RNase P/MRP complex. Mol Cell 2019; 74(3): 494–507.e8 https://doi.org/10.1016/j.molcel.2019.02.034
53	CR Alarcón, H Goodarzi, H Lee, X Liu, S Tavazoie, SF Tavazoie. HNRNPA2B1 is a mediator of m6A-dependent nuclear RNA processing events. Cell 2015; 162(6): 1299–1308 https://doi.org/10.1016/j.cell.2015.08.011
54	RX Chen, X Chen, LP Xia, JX Zhang, ZZ Pan, XD Ma, K Han, JW Chen, JG Judde, O Deas, F Wang, NF Ma, X Guan, JP Yun, FW Wang, RH Xu, D Xie. N6-methyladenosine modification of circNSUN2 facilitates cytoplasmic export and stabilizes HMGA2 to promote colorectal liver metastasis. Nat Commun 2019; 10(1): 4695 https://doi.org/10.1038/s41467-019-12651-2
55	Y Yang, X Fan, M Mao, X Song, P Wu, Y Zhang, Y Jin, Y Yang, LL Chen, Y Wang, CC Wong, X Xiao, Z Wang. Extensive translation of circular RNAs driven by N6-methyladenosine. Cell Res 2017; 27(5): 626–641 https://doi.org/10.1038/cr.2017.31
56	XL Ping, BF Sun, L Wang, W Xiao, X Yang, WJ Wang, S Adhikari, Y Shi, Y Lv, YS Chen, X Zhao, A Li, Y Yang, U Dahal, XM Lou, X Liu, J Huang, WP Yuan, XF Zhu, T Cheng, YL Zhao, X Wang, JM Rendtlew Danielsen, F Liu, YG Yang. Mammalian WTAP is a regulatory subunit of the RNA N6-methyladenosine methyltransferase. Cell Res 2014; 24(2): 177–189 https://doi.org/10.1038/cr.2014.3
57	J Choe, S Lin, W Zhang, Q Liu, L Wang, J Ramirez-Moya, P Du, W Kim, S Tang, P Sliz, P Santisteban, RE George, WG Richards, KK Wong, N Locker, FJ Slack, RI Gregory. mRNA circularization by METTL3-eIF3h enhances translation and promotes oncogenesis. Nature 2018; 561(7724): 556–560 https://doi.org/10.1038/s41586-018-0538-8
58	PY Bhattarai, G Kim, SC Lim, R Mariappan, T Ohn, HS Choi. METTL3 stabilization by PIN1 promotes breast tumorigenesis via enhanced m6A-dependent translation. Oncogene 2023; 42(13): 1010–1023 https://doi.org/10.1038/s41388-023-02617-6
59	F Yu, AC Zhu, S Liu, B Gao, Y Wang, N Khudaverdyan, C Yu, Q Wu, Y Jiang, J Song, L Jin, C He, Z Qian. RBM33 is a unique m6A RNA-binding protein that regulates ALKBH5 demethylase activity and substrate selectivity. Mol Cell 2023; 83(12): 2003–2019.e6 https://doi.org/10.1016/j.molcel.2023.05.010
60	H Song, Y Wang, R Wang, X Zhang, Y Liu, G Jia, PR Chen. SFPQ is an FTO-binding protein that facilitates the demethylation substrate preference. Cell Chem Biol 2020; 27(3): 283–291.e6 https://doi.org/10.1016/j.chembiol.2020.01.002
61	F Xu, J Li, M Ni, J Cheng, H Zhao, S Wang, X Zhou, X Wu. FBW7 suppresses ovarian cancer development by targeting the N6-methyladenosine binding protein YTHDF2. Mol Cancer 2021; 20(1): 45 https://doi.org/10.1186/s12943-021-01340-8
62	J Zhang, J Wei, R Sun, H Sheng, K Yin, Y Pan, R Jimenez, S Chen, XL Cui, Z Zou, Z Yue, MJ Emch, JR Hawse, L Wang, HH He, S Xia, B Han, C He, H Huang. A lncRNA from the FTO locus acts as a suppressor of the m6A writer complex and p53 tumor suppression signaling. Mol Cell 2023; 83(15): 2692–2708.e7 https://doi.org/10.1016/j.molcel.2023.06.024
63	H Yang, Y Hu, M Weng, X Liu, P Wan, Y Hu, M Ma, Y Zhang, H Xia, K Lv. Hypoxia inducible lncRNA-CBSLR modulates ferroptosis through m6A-YTHDF2-dependent modulation of CBS in gastric cancer. J Adv Res 2022; 37: 91–106 https://doi.org/10.1016/j.jare.2021.10.001
64	L Zhou, J Jiang, Z Huang, P Jin, L Peng, M Luo, Z Zhang, Y Chen, N Xie, W Gao, EC Nice, JQ Li, HN Chen, C Huang. Hypoxia-induced lncRNA STEAP3-AS1 activates Wnt/β-catenin signaling to promote colorectal cancer progression by preventing m6A-mediated degradation of STEAP3 mRNA. Mol Cancer 2022; 21(1): 168 https://doi.org/10.1186/s12943-022-01638-1
65	B Yao, Q Zhang, Z Yang, F An, H Nie, H Wang, C Yang, J Sun, K Chen, J Zhou, B Bai, S Gu, W Zhao, Q Zhan. CircEZH2/miR-133b/IGF2BP2 aggravates colorectal cancer progression via enhancing the stability of m6A-modified CREB1 mRNA. Mol Cancer 2022; 21(1): 140 https://doi.org/10.1186/s12943-022-01608-7
66	YL Deribe, T Pawson, I Dikic. Post-translational modifications in signal integration. Nat Struct Mol Biol 2010; 17(6): 666–672 https://doi.org/10.1038/nsmb.1842
67	J Liu, C Qian, X Cao. Post-translational modification control of innate immunity. Immunity 2016; 45(1): 15–30 https://doi.org/10.1016/j.immuni.2016.06.020
68	Y Li, X He, X Lu, Z Gong, Q Li, L Zhang, R Yang, C Wu, J Huang, J Ding, Y He, W Liu, C Chen, B Cao, D Zhou, Y Shi, J Chen, C Wang, S Zhang, J Zhang, J Ye, H You. METTL3 acetylation impedes cancer metastasis via fine-tuning its nuclear and cytosolic functions. Nat Commun 2022; 13(1): 6350 https://doi.org/10.1038/s41467-022-34209-5
69	Y Yang, Y He, X Wang, Z Liang, G He, P Zhang, H Zhu, N Xu, S Liang. Protein SUMOylation modification and its associations with disease. Open Biol 2017; 7(10): 170167 https://doi.org/10.1098/rsob.170167
70	C Zhu, C Chen, J Huang, H Zhang, X Zhao, R Deng, J Dou, H Jin, R Chen, M Xu, Q Chen, Y Wang, J Yu. SUMOylation at K707 of DGCR8 controls direct function of primary microRNA. Nucleic Acids Res 2015; 43(16): 7945–7960 https://doi.org/10.1093/nar/gkv741
71	C Chen, C Zhu, J Huang, X Zhao, R Deng, H Zhang, J Dou, Q Chen, M Xu, H Yuan, Y Wang, J Yu. SUMOylation of TARBP2 regulates miRNA/siRNA efficiency. Nat Commun 2015; 6: 8899 https://doi.org/10.1038/ncomms9899
72	Y Du, G Hou, H Zhang, J Dou, J He, Y Guo, L Li, R Chen, Y Wang, R Deng, J Huang, B Jiang, M Xu, J Cheng, GQ Chen, X Zhao, J Yu. SUMOylation of the m6A-RNA methyltransferase METTL3 modulates its function. Nucleic Acids Res 2018; 46(10): 5195–5208 https://doi.org/10.1093/nar/gky156
73	H Xu, H Wang, W Zhao, S Fu, Y Li, W Ni, Y Xin, W Li, C Yang, Y Bai, M Zhan, L Lu. SUMO1 modification of methyltransferase-like 3 promotes tumor progression via regulating Snail mRNA homeostasis in hepatocellular carcinoma. Theranostics 2020; 10(13): 5671–5686 https://doi.org/10.7150/thno.42539
74	X Liu, J Liu, W Xiao, Q Zeng, H Bo, Y Zhu, L Gong, D He, X Xing, R Li, M Zhou, W Xiong, Y Zhou, J Zhou, X Li, F Guo, C Xu, X Chen, X Wang, F Wang, Q Wang, K Cao. SIRT1 regulates N6-methyladenosine RNA modification in hepatocarcinogenesis by inducing RANBP2-dependent FTO SUMOylation. Hepatology 2020; 72(6): 2029–2050 https://doi.org/10.1002/hep.31222
75	G Hou, X Zhao, L Li, Q Yang, X Liu, C Huang, R Lu, R Chen, Y Wang, B Jiang, J Yu. SUMOylation of YTHDF2 promotes mRNA degradation and cancer progression by increasing its binding affinity with m6A-modified mRNAs. Nucleic Acids Res 2021; 49(5): 2859–2877 https://doi.org/10.1093/nar/gkab065
76	J Xiong, J He, J Zhu, J Pan, W Liao, H Ye, H Wang, Y Song, Y Du, B Cui, M Xue, W Zheng, X Kong, K Jiang, K Ding, L Lai, Q Wang. Lactylation-driven METTL3-mediated RNA m6A modification promotes immunosuppression of tumor-infiltrating myeloid cells. Mol Cell 2022; 82(9): 1660–1677.e10 https://doi.org/10.1016/j.molcel.2022.02.033
77	T Bilbrough, E Piemontese, O Seitz. Dissecting the role of protein phosphorylation: a chemical biology toolbox. Chem Soc Rev 2022; 51(13): 5691–5730 https://doi.org/10.1039/D1CS00991E
78	HL Sun, AC Zhu, Y Gao, H Terajima, Q Fei, S Liu, L Zhang, Z Zhang, BT Harada, YY He, MB Bissonnette, MC Hung, C He. Stabilization of ERK-phosphorylated METTL3 by USP5 increases m6A methylation. Mol Cell 2020; 80(4): 633–647.e7 https://doi.org/10.1016/j.molcel.2020.10.026
79	M Perez-Pepe, AW Desotell, H Li, W Li, B Han, Q Lin, DE Klein, Y Liu, H Goodarzi, CR Alarcón. 7SK methylation by METTL3 promotes transcriptional activity. Sci Adv 2023; 9(19): eade7500 https://doi.org/10.1126/sciadv.ade7500
80	R Fang, X Chen, S Zhang, H Shi, Y Ye, H Shi, Z Zou, P Li, Q Guo, L Ma, C He, S Huang. EGFR/SRC/ERK-stabilized YTHDF2 promotes cholesterol dysregulation and invasive growth of glioblastoma. Nat Commun 2021; 12(1): 177 https://doi.org/10.1038/s41467-020-20379-7
81	PE Cockram, M Kist, S Prakash, SH Chen, IE Wertz, D Vucic. Ubiquitination in the regulation of inflammatory cell death and cancer. Cell Death Differ 2021; 28(2): 591–605 https://doi.org/10.1038/s41418-020-00708-5
82	Y Gwon, BA Maxwell, RM Kolaitis, P Zhang, HJ Kim, JP Taylor. Ubiquitination of G3BP1 mediates stress granule disassembly in a context-specific manner. Science 2021; 372(6549): eabf6548 https://doi.org/10.1126/science.abf6548
83	J Huang, W Zhou, C Hao, Q He, X Tu. The feedback loop of METTL14 and USP38 regulates cell migration, invasion and EMT as well as metastasis in bladder cancer. PLoS Genet 2022; 18(10): e1010366 https://doi.org/10.1371/journal.pgen.1010366
84	Z Zhang, Q Gao, S Wang. Kinase GSK3β functions as a suppressor in colorectal carcinoma through the FTO-mediated MZF1/c-Myc axis. J Cell Mol Med 2021; 25(5): 2655–2665 https://doi.org/10.1111/jcmm.16291
85	W Song, K Yang, J Luo, Z Gao, Y Gao. Dysregulation of USP18/FTO/PYCR1 signaling network promotes bladder cancer development and progression. Aging (Albany NY) 2021; 13(3): 3909–3925 https://doi.org/10.18632/aging.202359
86	Z Wang, Z Pan, S Adhikari, BT Harada, L Shen, W Yuan, T Abeywardana, Q Al-Hadid, JM Stark, C He, L Lin, Y Yang. m6A deposition is regulated by PRMT1-mediated arginine methylation of METTL14 in its disordered C-terminal region. EMBO J 2021; 40(5): e106309 https://doi.org/10.15252/embj.2020106309
87	M Angelova, RF Ortiz-Meoz, S Walker, DM Knipe. Inhibition of O-linked N-acetylglucosamine transferase reduces replication of herpes simplex virus and human cytomegalovirus. J Virol 2015; 89(16): 8474–8483 https://doi.org/10.1128/JVI.01002-15
88	X Rao, X Duan, W Mao, X Li, Z Li, Q Li, Z Zheng, H Xu, M Chen, PG Wang, Y Wang, B Shen, W Yi. O-GlcNAcylation of G6PD promotes the pentose phosphate pathway and tumor growth. Nat Commun 2015; 6: 8468 https://doi.org/10.1038/ncomms9468
89	Y Yang, Y Yan, J Yin, N Tang, K Wang, L Huang, J Hu, Z Feng, Q Gao, A Huang. O-GlcNAcylation of YTHDF2 promotes HBV-related hepatocellular carcinoma progression in an N6-methyladenosine-dependent manner. Signal Transduct Target Ther 2023; 8(1): 63 https://doi.org/10.1038/s41392-023-01316-8
90	J Liu, K Li, J Cai, M Zhang, X Zhang, X Xiong, H Meng, X Xu, Z Huang, J Peng, J Fan, C Yi. Landscape and regulation of m6A and m6Am methylome across human and mouse tissues. Mol Cell 2020; 77(2): 426–440.e6 https://doi.org/10.1016/j.molcel.2019.09.032
91	S Dong, Y Wu, Y Liu, H Weng, H Huang. N6-methyladenosine steers RNA metabolism and regulation in cancer. Cancer Commun (Lond) 2021; 41(7): 538–559 https://doi.org/10.1002/cac2.12161
92	Z Xu, B Peng, Y Cai, G Wu, J Huang, M Gao, G Guo, S Zeng, Z Gong, Y Yan. N6-methyladenosine RNA modification in cancer therapeutic resistance: current status and perspectives. Biochem Pharmacol 2020; 182: 114258 https://doi.org/10.1016/j.bcp.2020.114258
93	LJ Deng, WQ Deng, SR Fan, MF Chen, M Qi, WY Lyu, Q Qi, AK Tiwari, JX Chen, DM Zhang, ZS Chen. m6A modification: recent advances, anticancer targeted drug discovery and beyond. Mol Cancer 2022; 21(1): 52 https://doi.org/10.1186/s12943-022-01510-2
94	Y Li, R Su, X Deng, Y Chen, J Chen. FTO in cancer: functions, molecular mechanisms, and therapeutic implications. Trends Cancer 2022; 8(7): 598–614 https://doi.org/10.1016/j.trecan.2022.02.010
95	MN Flamand, M Tegowski, KD Meyer. The proteins of mRNA modification: writers, readers, and erasers. Annu Rev Biochem 2023; 92: 145–173 https://doi.org/10.1146/annurev-biochem-052521-035330
96	Y Zhao, Y Shi, H Shen, W Xie. m6A-binding proteins: the emerging crucial performers in epigenetics. J Hematol Oncol 2020; 13(1): 35 https://doi.org/10.1186/s13045-020-00872-8
97	S Wang, S Gao, Y Zeng, L Zhu, Y Mo, CC Wong, Y Bao, P Su, J Zhai, L Wang, F Soares, X Xu, H Chen, K Hezaveh, X Ci, A He, T McGaha, C O'Brien, R Rottapel, W Kang, J Wu, G Zheng, Z Cai, J Yu, HH He. N6-methyladenosine reader YTHDF1 promotes ARHGEF2 translation and RhoA signaling in colorectal cancer. Gastroenterology 2022; 162(4): 1183–1196 https://doi.org/10.1053/j.gastro.2021.12.269
98	Y Bao, J Zhai, H Chen, CC Wong, C Liang, Y Ding, D Huang, H Gou, D Chen, Y Pan, W Kang, KF To, J Yu. Targeting m6A reader YTHDF1 augments antitumour immunity and boosts anti-PD-1 efficacy in colorectal cancer. Gut 2023; 72(8): 1497–1509 https://doi.org/10.1136/gutjnl-2022-328845
99	S GuoF Chen L LiS Dou Q LiY Huang Z LiW Liu G Zhang. Intracellular Fusobacterium nucleatum infection increases METTL3-mediated m6A methylation to promote the metastasis of esophageal squamous cell carcinoma. J Adv Res 2023; [Epub ahead of print] doi:10.1016/j.jare.2023.08.014
100	Y Pan, Y Gu, T Liu, Q Zhang, F Yang, L Duan, S Cheng, X Zhu, Y Xi, X Chang, Q Ye, S Gao. Epitranscriptic regulation of HRAS by N6-methyladenosine drives tumor progression. Proc Natl Acad Sci USA 2023; 120(14): e2302291120 https://doi.org/10.1073/pnas.2302291120
101	H Sheng, Z Li, S Su, W Sun, X Zhang, L Li, J Li, S Liu, B Lu, S Zhang, C Shan. YTH domain family 2 promotes lung cancer cell growth by facilitating 6-phosphogluconate dehydrogenase mRNA translation. Carcinogenesis 2020; 41(5): 541–550 https://doi.org/10.1093/carcin/bgz152
102	C Zhang, S Huang, H Zhuang, S Ruan, Z Zhou, K Huang, F Ji, Z Ma, B Hou, X He. YTHDF2 promotes the liver cancer stem cell phenotype and cancer metastasis by regulating OCT4 expression via m6A RNA methylation. Oncogene 2020; 39(23): 4507–4518 https://doi.org/10.1038/s41388-020-1303-7
103	Y Li, H Sheng, F Ma, Q Wu, J Huang, Q Chen, L Sheng, X Zhu, X Zhu, M Xu. RNA m6A reader YTHDF2 facilitates lung adenocarcinoma cell proliferation and metastasis by targeting the AXIN1/Wnt/β-catenin signaling. Cell Death Dis 2021; 12(5): 479 https://doi.org/10.1038/s41419-021-03763-z
104	RC Chai, YZ Chang, X Chang, B Pang, SY An, KN Zhang, YH Chang, T Jiang, YZ Wang. YTHDF2 facilitates UBXN1 mRNA decay by recognizing METTL3-mediated m6A modification to activate NF-κB and promote the malignant progression of glioma. J Hematol Oncol 2021; 14(1): 109 https://doi.org/10.1186/s13045-021-01124-z
105	J Paris, M Morgan, J Campos, GJ Spencer, A Shmakova, I Ivanova, C Mapperley, H Lawson, DA Wotherspoon, C Sepulveda, M Vukovic, L Allen, A Sarapuu, A Tavosanis, AV Guitart, A Villacreces, C Much, J Choe, A Azar, de Lagemaat LN van, D Vernimmen, A Nehme, F Mazurier, TCP Somervaille, RI Gregory, D O’Carroll, KR Kranc. Targeting the RNA m6A reader YTHDF2 selectively compromises cancer stem cells in acute myeloid leukemia. Cell Stem Cell 2019; 25(1): 137–148.e6 https://doi.org/10.1016/j.stem.2019.03.021
106	Y Xu, X He, S Wang, B Sun, R Jia, P Chai, F Li, Y Yang, S Ge, R Jia, YG Yang, X Fan. The m6A reading protein YTHDF3 potentiates tumorigenicity of cancer stem-like cells in ocular melanoma through facilitating CTNNB1 translation. Oncogene 2022; 41(9): 1281–1297 https://doi.org/10.1038/s41388-021-02146-0
107	G Chang, L Shi, Y Ye, H Shi, L Zeng, S Tiwary, JT Huse, L Huo, L Ma, Y Ma, S Zhang, J Zhu, V Xie, P Li, L Han, C He, S Huang. YTHDF3 induces the translation of m6A-enriched gene transcripts to promote breast cancer brain metastasis. Cancer Cell 2020; 38(6): 857–871.e7 https://doi.org/10.1016/j.ccell.2020.10.004
108	L Zhang, Y Wan, Z Zhang, Y Jiang, Z Gu, X Ma, S Nie, J Yang, J Lang, W Cheng, L Zhu. IGF2BP1 overexpression stabilizes PEG10 mRNA in an m6A-dependent manner and promotes endometrial cancer progression. Theranostics 2021; 11(3): 1100–1114 https://doi.org/10.7150/thno.49345
109	Y Liu, Q Guo, H Yang, XW Zhang, N Feng, JK Wang, TT Liu, KW Zeng, PF Tu. Allosteric regulation of IGF2BP1 as a novel strategy for the activation of tumor immune microenvironment. ACS Cent Sci 2022; 8(8): 1102–1115 https://doi.org/10.1021/acscentsci.2c00107
110	XT Huang, JH Li, XX Zhu, CS Huang, ZX Gao, QC Xu, W Zhao, XY Yin. HNRNPC impedes m6A-dependent anti-metastatic alternative splicing events in pancreatic ductal adenocarcinoma. Cancer Lett 2021; 518: 196–206 https://doi.org/10.1016/j.canlet.2021.07.016
111	M Sun, Y Shen, G Jia, Z Deng, F Shi, Y Jing, S Xia. Activation of the HNRNPA2B1/miR-93-5p/FRMD6 axis facilitates prostate cancer progression in an m6A-dependent manner. J Cancer 2023; 14(7): 1242–1256 https://doi.org/10.7150/jca.83863
112	L Zhong, D Liao, M Zhang, C Zeng, X Li, R Zhang, H Ma, T Kang. YTHDF2 suppresses cell proliferation and growth via destabilizing the EGFR mRNA in hepatocellular carcinoma. Cancer Lett. 2019; 442: 252–261 https://doi.org/10.1016/j.canlet.2018.11.006
113	L Ma, T Chen, X Zhang, Y Miao, X Tian, K Yu, X Xu, Y Niu, S Guo, C Zhang, S Qiu, Y Qiao, W Fang, L Du, Y Yu, J Wang. The m6A reader YTHDC2 inhibits lung adenocarcinoma tumorigenesis by suppressing SLC7A11-dependent antioxidant function. Redox Biol 2021; 38: 101801 https://doi.org/10.1016/j.redox.2020.101801
114	D Jin, J Guo, Y Wu, L Yang, X Wang, J Du, J Dai, W Chen, K Gong, S Miao, X Li, H Sun. m6A demethylase ALKBH5 inhibits tumor growth and metastasis by reducing YTHDFs-mediated YAP expression and inhibiting miR-107/LATS2-mediated YAP activity in NSCLC. Mol Cancer 2020; 19(1): 40 https://doi.org/10.1186/s12943-020-01161-1
115	P Zhu, F He, Y Hou, G Tu, Q Li, T Jin, H Zeng, Y Qin, X Wan, Y Qiao, Y Qiu, Y Teng, M Liu. A novel hypoxic long noncoding RNA KB-1980E6.3 maintains breast cancer stem cell stemness via interacting with IGF2BP1 to facilitate c-Myc mRNA stability. Oncogene 2021; 40(9): 1609–1627 https://doi.org/10.1038/s41388-020-01638-9
116	T Su, M Huang, J Liao, S Lin, P Yu, J Yang, Y Cai, S Zhu, L Xu, Z Peng, S Peng, S Chen, M Kuang. Insufficient radiofrequency ablation promotes hepatocellular carcinoma metastasis through N6-methyladenosine mRNA methylation-dependent mechanism. Hepatology 2021; 74(3): 1339–1356 https://doi.org/10.1002/hep.31766
117	L Liu, J He, G Sun, N Huang, Z Bian, C Xu, Y Zhang, Z Cui, W Xu, F Sun, C Zhuang, Q Man, S Gu. The N6-methyladenosine modification enhances ferroptosis resistance through inhibiting SLC7A11 mRNA deadenylation in hepatoblastoma. Clin Transl Med 2022; 12(5): e778 https://doi.org/10.1002/ctm2.778
118	J Tian, P Ying, J Ke, Y Zhu, Y Yang, Y Gong, D Zou, X Peng, N Yang, X Wang, S Mei, Y Zhang, C Wang, R Zhong, J Chang, X Miao. ANKLE1 N6-methyladenosine-related variant is associated with colorectal cancer risk by maintaining the genomic stability. Int J Cancer 2020; 146(12): 3281–3293 https://doi.org/10.1002/ijc.32677
119	L Wang, L Zhu, C Liang, X Huang, Z Liu, J Huo, Y Zhang, Y Zhang, L Chen, H Xu, X Li, L Xu, M Kuang, CC Wong, J Yu. Targeting N6-methyladenosine reader YTHDF1 with siRNA boosts antitumor immunity in NASH-HCC by inhibiting EZH2-IL-6 axis. J Hepatol 2023; 79(5): 1185–1200 https://doi.org/10.1016/j.jhep.2023.06.021
120	Z Lin, Y Niu, A Wan, D Chen, H Liang, X Chen, L Sun, S Zhan, L Chen, C Cheng, X Zhang, X Bu, W He, G Wan. RNA m6A methylation regulates sorafenib resistance in liver cancer through FOXO3-mediated autophagy. EMBO J 2020; 39(12): e103181 https://doi.org/10.15252/embj.2019103181
121	X Li, S Ma, Y Deng, P Yi, J Yu. Targeting the RNA m6A modification for cancer immunotherapy. Mol Cancer 2022; 21(1): 76 https://doi.org/10.1186/s12943-022-01558-0
122	E Yankova, W Blackaby, M Albertella, J Rak, E De Braekeleer, G Tsagkogeorga, ES Pilka, D Aspris, D Leggate, AG Hendrick, NA Webster, B Andrews, R Fosbeary, P Guest, N Irigoyen, M Eleftheriou, M Gozdecka, JML Dias, AJ Bannister, B Vick, I Jeremias, GS Vassiliou, O Rausch, K Tzelepis, T Kouzarides. Small-molecule inhibition of METTL3 as a strategy against myeloid leukaemia. Nature 2021; 593(7860): 597–601 https://doi.org/10.1038/s41586-021-03536-w
123	A Dolbois, RK Bedi, E Bochenkova, A Müller, EV Moroz-Omori, D Huang, A Caflisch. 1,4,9-triazaspiro[5.5]undecan-2-one derivatives as potent and selective METTL3 inhibitors. J Med Chem 2021; 64(17): 12738–12760 https://doi.org/10.1021/acs.jmedchem.1c00773
124	EV Moroz-Omori, D Huang, R Kumar Bedi, SJ Cheriyamkunnel, E Bochenkova, A Dolbois, MD Rzeczkowski, Y Li, L Wiedmer, A Caflisch. METTL3 inhibitors for epitranscriptomic modulation of cellular processes. ChemMedChem 2021; 16(19): 3035–3043 https://doi.org/10.1002/cmdc.202100291
125	JH Lee, N Choi, S Kim, MS Jin, H Shen, YC Kim. Eltrombopag as an allosteric inhibitor of the METTL3-14 complex affecting the m6A methylation of RNA in acute myeloid leukemia cells. Pharmaceuticals (Basel) 2022; 15(4): 440 https://doi.org/10.3390/ph15040440
126	PA Boriack-Sjodin, S Ribich, RA Copeland. RNA-modifying proteins as anticancer drug targets. Nat Rev Drug Discov 2018; 17(6): 435–453 https://doi.org/10.1038/nrd.2018.71
127	F Fiorentino, M Menna, D Rotili, S Valente, A Mai. METTL3 from target validation to the first small-molecule inhibitors: a medicinal chemistry journey. J Med Chem 2023; 66(3): 1654–1677 https://doi.org/10.1021/acs.jmedchem.2c01601
128	B Chen, F Ye, L Yu, G Jia, X Huang, X Zhang, S Peng, K Chen, M Wang, S Gong, R Zhang, J Yin, H Li, Y Yang, H Liu, J Zhang, H Zhang, A Zhang, H Jiang, C Luo, CG Yang. Development of cell-active N6-methyladenosine RNA demethylase FTO inhibitor. J Am Chem Soc 2012; 134(43): 17963–17971 https://doi.org/10.1021/ja3064149
129	Y Huang, J Yan, Q Li, J Li, S Gong, H Zhou, J Gan, H Jiang, GF Jia, C Luo, CG Yang. Meclofenamic acid selectively inhibits FTO demethylation of m6A over ALKBH5. Nucleic Acids Res 2015; 43(1): 373–384 https://doi.org/10.1093/nar/gku1276
130	Y Huang, R Su, Y Sheng, L Dong, Z Dong, H Xu, T Ni, ZS Zhang, T Zhang, C Li, L Han, Z Zhu, F Lian, J Wei, Q Deng, Y Wang, M Wunderlich, Z Gao, G Pan, D Zhong, H Zhou, N Zhang, J Gan, H Jiang, JC Mulloy, Z Qian, J Chen, CG Yang. Small-molecule targeting of oncogenic FTO demethylase in acute myeloid leukemia. Cancer Cell 2019; 35(4): 677–691.e10 https://doi.org/10.1016/j.ccell.2019.03.006
131	Y Liu, G Liang, H Xu, W Dong, Z Dong, Z Qiu, Z Zhang, F Li, Y Huang, Y Li, J Wu, S Yin, Y Zhang, P Guo, J Liu, JJ Xi, P Jiang, D Han, CG Yang, MM Xu. Tumors exploit FTO-mediated regulation of glycolytic metabolism to evade immune surveillance. Cell Metab 2021; 33(6): 1221–1233.e11 https://doi.org/10.1016/j.cmet.2021.04.001
132	R Su, L Dong, C Li, S Nachtergaele, M Wunderlich, Y Qing, X Deng, Y Wang, X Weng, C Hu, M Yu, J Skibbe, Q Dai, D Zou, T Wu, K Yu, H Weng, H Huang, K Ferchen, X Qin, B Zhang, J Qi, AT Sasaki, DR Plas, JE Bradner, M Wei, G Marcucci, X Jiang, JC Mulloy, J Jin, C He, J Chen. R-2HG exhibits anti-tumor activity by targeting FTO/m6A/MYC/CEBPA signaling. Cell 2018; 172(1–2): 90–105.e23 https://doi.org/10.1016/j.cell.2017.11.031
133	R Su, L Dong, Y Li, M Gao, L Han, M Wunderlich, X Deng, H Li, Y Huang, L Gao, C Li, Z Zhao, S Robinson, B Tan, Y Qing, X Qin, E Prince, J Xie, H Qin, W Li, C Shen, J Sun, P Kulkarni, H Weng, H Huang, Z Chen, B Zhang, X Wu, MJ Olsen, M Müschen, G Marcucci, R Salgia, L Li, AT Fathi, Z Li, JC Mulloy, M Wei, D Horne, J Chen. Targeting FTO suppresses cancer stem cell maintenance and immune evasion. Cancer Cell 2020; 38(1): 79–96.e11 https://doi.org/10.1016/j.ccell.2020.04.017
134	S Selberg, N Seli, E Kankuri, M Karelson. Rational design of novel anticancer small-molecule RNA m6A demethylase ALKBH5 inhibitors. ACS Omega 2021; 6(20): 13310–13320 https://doi.org/10.1021/acsomega.1c01289
135	RW Sabnis. Novel small molecule RNA m6A demethylase AlkBH5 inhibitors for treating cancer. ACS Med Chem Lett 2021; 12(6): 856–857 https://doi.org/10.1021/acsmedchemlett.1c00102
136	A Malacrida, M Rivara, A Di Domizio, G Cislaghi, M Miloso, V Zuliani, G Nicolini. 3D proteome-wide scale screening and activity evaluation of a new ALKBH5 inhibitor in U87 glioblastoma cell line. Bioorg Med Chem 2020; 28(4): 115300 https://doi.org/10.1016/j.bmc.2019.115300
137	M Micaelli, A Dalle Vedove, L Cerofolini, J Vigna, D Sighel, S Zaccara, I Bonomo, G Poulentzas, EF Rosatti, G Cazzanelli, L Alunno, R Belli, D Peroni, E Dassi, S Murakami, SR Jaffrey, M Fragai, I Mancini, G Lolli, A Quattrone, A Provenzani. Small-molecule ebselen binds to YTHDF proteins interfering with the recognition of N6-methyladenosine-modified RNAs. ACS Pharmacol Transl Sci 2022; 5(10): 872–891 https://doi.org/10.1021/acsptsci.2c00008
138	S Ma, B Sun, S Duan, J Han, T Barr, J Zhang, MB Bissonnette, M Kortylewski, C He, J Chen, MA Caligiuri, J Yu. YTHDF2 orchestrates tumor-associated macrophage reprogramming and controls antitumor immunity through CD8+ T cells. Nat Immunol 2023; 24(2): 255–266 https://doi.org/10.1038/s41590-022-01398-6
139	L Wang, X Dou, S Chen, X Yu, X Huang, L Zhang, Y Chen, J Wang, K Yang, J Bugno, S Pitroda, X Ding, A Piffko, W Si, C Chen, H Jiang, B Zhou, SJ Chmura, C Luo, HL Liang, C He, RR Weichselbaum. YTHDF2 inhibition potentiates radiotherapy antitumor efficacy. Cancer Cell 2023; 41(7): 1294–1308.e8 https://doi.org/10.1016/j.ccell.2023.04.019
140	H Weng, F Huang, Z Yu, Z Chen, E Prince, Y Kang, K Zhou, W Li, J Hu, C Fu, T Aziz, H Li, J Li, Y Yang, L Han, S Zhang, Y Ma, M Sun, H Wu, Z Zhang, M Wunderlich, S Robinson, D Braas, JT Hoeve, B Zhang, G Marcucci, JC Mulloy, K Zhou, HF Tao, X Deng, D Horne, M Wei, H Huang, J Chen. The m6A reader IGF2BP2 regulates glutamine metabolism and represents a therapeutic target in acute myeloid leukemia. Cancer Cell 2022; 40(12): 1566–1582.e10 https://doi.org/10.1016/j.ccell.2022.10.004
141	Y Pan, H Chen, X Zhang, W Liu, Y Ding, D Huang, J Zhai, W Wei, J Wen, D Chen, Y Zhou, C Liang, N Wong, K Man, AH Cheung, CC Wong, J Yu. METTL3 drives NAFLD-related hepatocellular carcinoma and is a therapeutic target for boosting immunotherapy. Cell Rep Med 2023; 4(8): 101144 https://doi.org/10.1016/j.xcrm.2023.101144
142	L Xiao, X Li, Z Mu, J Zhou, P Zhou, C Xie, S Jiang. FTO inhibition enhances the antitumor effect of temozolomide by targeting MYC-miR-155/23a cluster-MXI1 feedback circuit in glioma. Cancer Res 2020; 80(18): 3945–3958 https://doi.org/10.1158/0008-5472.CAN-20-0132
143	D Dominissini, S Nachtergaele, S Moshitch-Moshkovitz, E Peer, N Kol, MS Ben-Haim, Q Dai, Segni A Di, M Salmon-Divon, WC Clark, G Zheng, T Pan, O Solomon, E Eyal, V Hershkovitz, D Han, LC Doré, N Amariglio, G Rechavi, C He. The dynamic N1-methyladenosine methylome in eukaryotic messenger RNA. Nature 2016; 530(7591): 441–446 https://doi.org/10.1038/nature16998
144	X Li, X Xiong, K Wang, L Wang, X Shu, S Ma, C Yi. Transcriptome-wide mapping reveals reversible and dynamic N1-methyladenosine methylome. Nat Chem Biol 2016; 12(5): 311–316 https://doi.org/10.1038/nchembio.2040
145	KW Seo, RE Kleiner. YTHDF2 recognition of N1-methyladenosine (m1A)-modified RNA is associated with transcript destabilization. ACS Chem Biol 2020; 15(1): 132–139 https://doi.org/10.1021/acschembio.9b00655
146	HH Woo, SK Chambers. Human ALKBH3-induced m1A demethylation increases the CSF-1 mRNA stability in breast and ovarian cancer cells. Biochim Biophys Acta Gene Regul Mech 2019; 1862(1): 35–46 https://doi.org/10.1016/j.bbagrm.2018.10.008
147	Z Chen, M Qi, B Shen, G Luo, Y Wu, J Li, Z Lu, Z Zheng, Q Dai, H Wang. Transfer RNA demethylase ALKBH3 promotes cancer progression via induction of tRNA-derived small RNAs. Nucleic Acids Res 2019; 47(5): 2533–2545 https://doi.org/10.1093/nar/gky1250
148	U Richter, ME Evans, WC Clark, P Marttinen, EA Shoubridge, A Suomalainen, A Wredenberg, A Wedell, T Pan, BJ Battersby. RNA modification landscape of the human mitochondrial tRNALys regulates protein synthesis. Nat Commun 2018; 9(1): 3966 https://doi.org/10.1038/s41467-018-06471-z
149	Y Wang, J Wang, X Li, X Xiong, J Wang, Z Zhou, X Zhu, Y Gu, D Dominissini, L He, Y Tian, C Yi, Z Fan. N1-methyladenosine methylation in tRNA drives liver tumourigenesis by regulating cholesterol metabolism. Nat Commun 2021; 12(1): 6314 https://doi.org/10.1038/s41467-021-26718-6
150	D Bar-Yaacov, I Frumkin, Y Yashiro, T Chujo, Y Ishigami, Y Chemla, A Blumberg, O Schlesinger, P Bieri, B Greber, N Ban, R Zarivach, L Alfonta, Y Pilpel, T Suzuki, D Mishmar. Mitochondrial 16S rRNA is methylated by tRNA methyltransferase TRMT61B in all vertebrates. PLoS Biol 2016; 14(9): e1002557 https://doi.org/10.1371/journal.pbio.1002557
151	S Sharma, JD Hartmann, P Watzinger, A Klepper, C Peifer, P Kötter, DLJ Lafontaine, KD Entian. A single N1-methyladenosine on the large ribosomal subunit rRNA impacts locally its structure and the translation of key metabolic enzymes. Sci Rep 2018; 8(1): 11904 https://doi.org/10.1038/s41598-018-30383-z
152	T Waku, Y Nakajima, W Yokoyama, N Nomura, K Kako, A Kobayashi, T Shimizu, A Fukamizu. NML-mediated rRNA base methylation links ribosomal subunit formation to cell proliferation in a p53-dependent manner. J Cell Sci 2016; 129(12): 2382–2393 https://doi.org/10.1242/jcs.183723
153	Q Tang, L Li, Y Wang, P Wu, X Hou, J Ouyang, C Fan, Z Li, F Wang, C Guo, M Zhou, Q Liao, H Wang, B Xiang, W Jiang, G Li, Z Zeng, W Xiong. RNA modifications in cancer. Br J Cancer 2023; 129(2): 204–221 https://doi.org/10.1038/s41416-023-02275-1
154	J Wei, F Liu, Z Lu, Q Fei, Y Ai, PC He, H Shi, X Cui, R Su, A Klungland, G Jia, J Chen, C He. Differential m6A, m6Am, and m1A demethylation mediated by FTO in the cell nucleus and cytoplasm. Mol Cell 2018; 71(6): 973–985.e5 https://doi.org/10.1016/j.molcel.2018.08.011
155	Q Zheng, H Gan, F Yang, Y Yao, F Hao, L Hong, L Jin. Cytoplasmic m1A reader YTHDF3 inhibits trophoblast invasion by downregulation of m1A-methylated IGF1R. Cell Discov 2020; 6: 12 https://doi.org/10.1038/s41421-020-0144-4
156	X Dai, T Wang, G Gonzalez, Y Wang. Identification of YTH domain-containing proteins as the readers for N1-methyladenosine in RNA. Anal Chem 2018; 90(11): 6380–6384 https://doi.org/10.1021/acs.analchem.8b01703
157	R García-Vílchez, A Sevilla, S Blanco. Post-transcriptional regulation by cytosine-5 methylation of RNA. Biochim Biophys Acta Gene Regul Mech 2019; 1862(3): 240–252 https://doi.org/10.1016/j.bbagrm.2018.12.003
158	F Tuorto, R Liebers, T Musch, M Schaefer, S Hofmann, S Kellner, M Frye, M Helm, G Stoecklin, F Lyko. RNA cytosine methylation by Dnmt2 and NSun2 promotes tRNA stability and protein synthesis. Nat Struct Mol Biol 2012; 19(9): 900–905 https://doi.org/10.1038/nsmb.2357
159	R Shanmugam, J Fierer, S Kaiser, M Helm, TP Jurkowski, A Jeltsch. Cytosine methylation of tRNA-Asp by DNMT2 has a role in translation of proteins containing poly-Asp sequences. Cell Discov 2015; 1: 15010 https://doi.org/10.1038/celldisc.2015.10
160	MD Metodiev, H Spåhr, Polosa P Loguercio, C Meharg, C Becker, J Altmueller, B Habermann, NG Larsson, B Ruzzenente. NSUN4 is a dual function mitochondrial protein required for both methylation of 12S rRNA and coordination of mitoribosomal assembly. PLoS Genet 2014; 10(2): e1004110 https://doi.org/10.1371/journal.pgen.1004110
161	X Dai, G Gonzalez, L Li, J Li, C You, W Miao, J Hu, L Fu, Y Zhao, R Li, L Li, X Chen, Y Xu, W Gu, Y Wang. YTHDF2 binds to 5-methylcytosine in RNA and modulates the maturation of ribosomal RNA. Anal Chem 2020; 92(1): 1346–1354 https://doi.org/10.1021/acs.analchem.9b04505
162	C Heissenberger, L Liendl, F Nagelreiter, Y Gonskikh, G Yang, EM Stelzer, TL Krammer, L Micutkova, S Vogt, DP Kreil, G Sekot, E Siena, I Poser, E Harreither, A Linder, V Ehret, TH Helbich, R Grillari-Voglauer, P Jansen-Dürr, M Koš, N Polacek, J Grillari, M Schosserer. Loss of the ribosomal RNA methyltransferase NSUN5 impairs global protein synthesis and normal growth. Nucleic Acids Res 2019; 47(22): 11807–11825 https://doi.org/10.1093/nar/gkz1043
163	X Yang, Y Yang, BF Sun, YS Chen, JW Xu, WY Lai, A Li, X Wang, DP Bhattarai, W Xiao, HY Sun, Q Zhu, HL Ma, S Adhikari, M Sun, YJ Hao, B Zhang, CM Huang, N Huang, GB Jiang, YL Zhao, HL Wang, YP Sun, YG Yang. 5-methylcytosine promotes mRNA export—NSUN2 as the methyltransferase and ALYREF as an m5C reader. Cell Res 2017; 27(5): 606–625 https://doi.org/10.1038/cr.2017.55
164	T Amort, D Rieder, A Wille, D Khokhlova-Cubberley, C Riml, L Trixl, XY Jia, R Micura, A Lusser. Distinct 5-methylcytosine profiles in poly(A) RNA from mouse embryonic stem cells and brain. Genome Biol 2017; 18(1): 1 https://doi.org/10.1186/s13059-016-1139-1
165	J Su, G Wu, Y Ye, J Zhang, L Zeng, X Huang, Y Zheng, R Bai, L Zhuang, M Li, L Pan, J Deng, R Li, S Deng, S Zhang, Z Zuo, Z Liu, J Lin, D Lin, J Zheng. NSUN2-mediated RNA 5-methylcytosine promotes esophageal squamous cell carcinoma progression via LIN28B-dependent GRB2 mRNA stabilization. Oncogene 2021; 40(39): 5814–5828 https://doi.org/10.1038/s41388-021-01978-0
166	T Selmi, S Hussain, S Dietmann, M Heiß, K Borland, S Flad, JM Carter, R Dennison, YL Huang, S Kellner, S Bornelöv, M Frye. Sequence- and structure-specific cytosine-5 mRNA methylation by NSUN6. Nucleic Acids Res 2021; 49(2): 1006–1022 https://doi.org/10.1093/nar/gkaa1193
167	X Chen, A Li, BF Sun, Y Yang, YN Han, X Yuan, RX Chen, WS Wei, Y Liu, CC Gao, YS Chen, M Zhang, XD Ma, ZW Liu, JH Luo, C Lyu, HL Wang, J Ma, YL Zhao, FJ Zhou, Y Huang, D Xie, YG Yang. 5-methylcytosine promotes pathogenesis of bladder cancer through stabilizing mRNAs. Nat Cell Biol 2019; 21(8): 978–990 https://doi.org/10.1038/s41556-019-0361-y
168	L Van Haute, S Dietmann, L Kremer, S Hussain, SF Pearce, CA Powell, J Rorbach, R Lantaff, S Blanco, S Sauer, U Kotzaeridou, GF Hoffmann, Y Memari, A Kolb-Kokocinski, R Durbin, JA Mayr, M Frye, H Prokisch, M Minczuk. Deficient methylation and formylation of mt-tRNA(Met) wobble cytosine in a patient carrying mutations in NSUN3. Nat Commun 2016; 7: 12039 https://doi.org/10.1038/ncomms12039
169	S Nakano, T Suzuki, L Kawarada, H Iwata, K Asano, T Suzuki. NSUN3 methylase initiates 5-formylcytidine biogenesis in human mitochondrial tRNA(Met). Nat Chem Biol 2016; 12(7): 546–551 https://doi.org/10.1038/nchembio.2099
170	J Liu, T Huang, Y Zhang, T Zhao, X Zhao, W Chen, R Zhang. Sequence- and structure-selective mRNA m5C methylation by NSUN6 in animals. Natl Sci Rev 2021; 8(6): nwaa273 https://doi.org/10.1093/nsr/nwaa273
171	H Yang, Y Wang, Y Xiang, T Yadav, J Ouyang, L Phoon, X Zhu, Y Shi, L Zou, L Lan. FMRP promotes transcription-coupled homologous recombination via facilitating TET1-mediated m5C RNA modification demethylation. Proc Natl Acad Sci USA 2022; 119(12): e2116251119 https://doi.org/10.1073/pnas.2116251119
172	H Shen, RJ Ontiveros, MC Owens, MY Liu, U Ghanty, RM Kohli, KF Liu. TET-mediated 5-methylcytosine oxidation in tRNA promotes translation. J Biol Chem 2021; 296: 100087 https://doi.org/10.1074/jbc.RA120.014226
173	L Kawarada, T Suzuki, T Ohira, S Hirata, K Miyauchi, T Suzuki. ALKBH1 is an RNA dioxygenase responsible for cytoplasmic and mitochondrial tRNA modifications. Nucleic Acids Res 2017; 45(12): 7401–7415 https://doi.org/10.1093/nar/gkx354
174	JZ Wang, W Zhu, J Han, X Yang, R Zhou, HC Lu, H Yu, WB Yuan, PC Li, J Tao, Q Lu, JF Wei, H Yang. The role of the HIF-1α/ALYREF/PKM2 axis in glycolysis and tumorigenesis of bladder cancer. Cancer Commun (Lond) 2021; 41(7): 560–575 https://doi.org/10.1002/cac2.12158
175	W Gao, L Chen, L Lin, M Yang, T Li, H Wei, C Sha, J Xing, M Zhang, S Zhao, Q Chen, W Xu, Y Li, X Zhu. SIAH1 reverses chemoresistance in epithelial ovarian cancer via ubiquitination of YBX-1. Oncogenesis 2022; 11(1): 13 https://doi.org/10.1038/s41389-022-00387-6
176	Y Yang, L Wang, X Han, WL Yang, M Zhang, HL Ma, BF Sun, A Li, J Xia, J Chen, J Heng, B Wu, YS Chen, JW Xu, X Yang, H Yao, J Sun, C Lyu, HL Wang, Y Huang, YP Sun, YL Zhao, A Meng, J Ma, F Liu, YG Yang. RNA 5-methylcytosine facilitates the maternal-to-zygotic transition by preventing maternal mRNA decay. Mol Cell 2019; 75(6): 1188–1202.e11 https://doi.org/10.1016/j.molcel.2019.06.033
177	Y Hu, C Chen, X Tong, S Chen, X Hu, B Pan, X Sun, Z Chen, X Shi, Y Hu, X Shen, X Xue, M Lu. NSUN2 modified by SUMO-2/3 promotes gastric cancer progression and regulates mRNA m5C methylation. Cell Death Dis 2021; 12(9): 842 https://doi.org/10.1038/s41419-021-04127-3
178	Z Sun, S Xue, M Zhang, H Xu, X Hu, S Chen, Y Liu, M Guo, H Cui. Aberrant NSUN2-mediated m5C modification of H19 lncRNA is associated with poor differentiation of hepatocellular carcinoma. Oncogene 2020; 39(45): 6906–6919 https://doi.org/10.1038/s41388-020-01475-w
179	L Mei, C Shen, R Miao, JZ Wang, MD Cao, YS Zhang, LH Shi, GH Zhao, MH Wang, LS Wu, JF Wei. RNA methyltransferase NSUN2 promotes gastric cancer cell proliferation by repressing p57Kip2 by an m5C-dependent manner. Cell Death Dis 2020; 11(4): 270 https://doi.org/10.1038/s41419-020-2487-z
180	H Song, J Zhang, B Liu, J Xu, B Cai, H Yang, J Straube, X Yu, T Ma. Biological roles of RNA m5C modification and its implications in cancer immunotherapy. Biomark Res 2022; 10(1): 15 https://doi.org/10.1186/s40364-022-00362-8
181	C Tomikawa. 7-methylguanosine modifications in transfer RNA (tRNA). Int J Mol Sci 2018; 19(12): 4080 https://doi.org/10.3390/ijms19124080
182	Y Furuichi. Discovery of m7G-cap in eukaryotic mRNAs. Proc Jpn Acad, Ser B, Phys Biol Sci 2015; 91(8): 394–409 https://doi.org/10.2183/pjab.91.394
183	L Malbec, T Zhang, YS Chen, Y Zhang, BF Sun, BY Shi, YL Zhao, Y Yang, YG Yang. Dynamic methylome of internal mRNA N7-methylguanosine and its regulatory role in translation. Cell Res 2019; 29(11): 927–941 https://doi.org/10.1038/s41422-019-0230-z
184	VS Zueva, AS Mankin, AA Bogdanov, LA Baratova. Specific fragmentation of tRNA and rRNA at a 7-methylguanine residue in the presence of methylated carrier RNA. Eur J Biochem 1985; 146(3): 679–687 https://doi.org/10.1111/j.1432-1033.1985.tb08704.x
185	Z Zhao, Y Qing, L Dong, L Han, D Wu, Y Li, W Li, J Xue, K Zhou, M Sun, B Tan, Z Chen, C Shen, L Gao, A Small, K Wang, K Leung, Z Zhang, X Qin, X Deng, Q Xia, R Su, J Chen. QKI shuttles internal m7G-modified transcripts into stress granules and modulates mRNA metabolism. Cell 2023; 186(15): 3208–3226.e27 https://doi.org/10.1016/j.cell.2023.05.047
186	S Lin, Q Liu, VS Lelyveld, J Choe, JW Szostak, RI Gregory. Mettl1/Wdr4-mediated m7G tRNA methylome is required for normal mRNA translation and embryonic stem cell self-renewal and differentiation. Mol Cell 2018; 71(2): 244–255.e5 https://doi.org/10.1016/j.molcel.2018.06.001
187	JA Bueren-Calabuig, MG Bage, VH Cowling, AV Pisliakov. Mechanism of allosteric activation of human mRNA cap methyltransferase (RNMT) by RAM: insights from accelerated molecular dynamics simulations. Nucleic Acids Res 2019; 47(16): 8675–8692 https://doi.org/10.1093/nar/gkz613
188	T Gonatopoulos-Pournatzis, S Dunn, R Bounds, VH Cowling. RAM/Fam103a1 is required for mRNA cap methylation. Mol Cell 2011; 44(4): 585–596 https://doi.org/10.1016/j.molcel.2011.08.041
189	J Ma, H Han, Y Huang, C Yang, S Zheng, T Cai, J Bi, X Huang, R Liu, L Huang, Y Luo, W Li, S Lin. METTL1/WDR4-mediated m7G tRNA modifications and m7G codon usage promote mRNA translation and lung cancer progression. Mol Ther 2021; 29(12): 3422–3435 https://doi.org/10.1016/j.ymthe.2021.08.005
190	Z Chen, W Zhu, S Zhu, K Sun, J Liao, H Liu, Z Dai, H Han, X Ren, Q Yang, S Zheng, B Peng, S Peng, M Kuang, S Lin. METTL1 promotes hepatocarcinogenesis via m7 G tRNA modification-dependent translation control. Clin Transl Med 2021; 11(12): e661 https://doi.org/10.1002/ctm2.661
191	J Chen, K Li, J Chen, X Wang, R Ling, M Cheng, Z Chen, F Chen, Q He, S Li, C Zhang, Y Jiang, Q Chen, A Wang, D Chen. Aberrant translation regulated by METTL1/WDR4-mediated tRNA N7-methylguanosine modification drives head and neck squamous cell carcinoma progression. Cancer Commun (Lond) 2022; 42(3): 223–244 https://doi.org/10.1002/cac2.12273
192	B Chen, W Jiang, Y Huang, J Zhang, P Yu, L Wu, H Peng. N7-methylguanosine tRNA modification promotes tumorigenesis and chemoresistance through WNT/β-catenin pathway in nasopharyngeal carcinoma. Oncogene 2022; 41(15): 2239–2253 https://doi.org/10.1038/s41388-022-02250-9
193	S Haag, J Kretschmer, MT Bohnsack. WBSCR22/Merm1 is required for late nuclear pre-ribosomal RNA processing and mediates N7-methylation of G1639 in human 18S rRNA. RNA 2015; 21(2): 180–187 https://doi.org/10.1261/rna.047910.114
194	C Zorbas, E Nicolas, L Wacheul, E Huvelle, V Heurgué-Hamard, DL Lafontaine. The human 18S rRNA base methyltransferases DIMT1L and WBSCR22-TRMT112 but not rRNA modification are required for ribosome biogenesis. Mol Biol Cell 2015; 26(11): 2080–2095 https://doi.org/10.1091/mbc.E15-02-0073
195	M Cai, C Yang, Z Wang. N7-methylguanosine modification: from regulatory roles to therapeutic implications in cancer. Am J Cancer Res 2023; 13(5): 1640–1655
196	M Kiriakidou, GS Tan, S Lamprinaki, M De Planell-Saguer, PT Nelson, Z Mourelatos. An mRNA m7G cap binding-like motif within human Ago2 represses translation. Cell 2007; 129(6): 1141–1151 https://doi.org/10.1016/j.cell.2007.05.016
197	N Cohen, M Sharma, A Kentsis, JM Perez, S Strudwick, KL Borden. PML RING suppresses oncogenic transformation by reducing the affinity of eIF4E for mRNA. EMBO J 2001; 20(16): 4547–4559 https://doi.org/10.1093/emboj/20.16.4547
198	M Aregger, A Kaskar, D Varshney, ME Fernandez-Sanchez, FA Inesta-Vaquera, S Weidlich, VH Cowling. CDK1-cyclin B1 activates RNMT, coordinating mRNA cap methylation with G1 phase transcription. Mol Cell 2016; 61(5): 734–746 https://doi.org/10.1016/j.molcel.2016.02.008
199	LS D’Abronzo, PM Ghosh. eIF4E phosphorylation in prostate cancer. Neoplasia 2018; 20(6): 563–573 https://doi.org/10.1016/j.neo.2018.04.003
200	X Ying, B Liu, Z Yuan, Y Huang, C Chen, X Jiang, H Zhang, D Qi, S Yang, S Lin, J Luo, W Ji. METTL1-m7 G-EGFR/EFEMP1 axis promotes the bladder cancer development. Clin Transl Med 2021; 11(12): e675 https://doi.org/10.1002/ctm2.675
201	A Kentsis, I Topisirovic, B Culjkovic, L Shao, KL Borden. Ribavirin suppresses eIF4E-mediated oncogenic transformation by physical mimicry of the 7-methyl guanosine mRNA cap. Proc Natl Acad Sci USA 2004; 101(52): 18105–18110 https://doi.org/10.1073/pnas.0406927102
202	H Sun, M Zhang, K Li, D Bai, C Yi. Cap-specific, terminal N6-methylation by a mammalian m6Am methyltransferase. Cell Res 2019; 29(1): 80–82 https://doi.org/10.1038/s41422-018-0117-4
203	J Mauer, M Sindelar, V Despic, T Guez, BR Hawley, JJ Vasseur, A Rentmeister, SS Gross, L Pellizzoni, F Debart, H Goodarzi, SR Jaffrey. FTO controls reversible m6Am RNA methylation during snRNA biogenesis. Nat Chem Biol 2019; 15(4): 340–347 https://doi.org/10.1038/s41589-019-0231-8
204	E Sendinc, D Valle-Garcia, A Dhall, H Chen, T Henriques, J Navarrete-Perea, W Sheng, SP Gygi, K Adelman, Y Shi. PCIF1 catalyzes m6Am mRNA methylation to regulate gene expression. Mol Cell 2019; 75(3): 620–630.e9 https://doi.org/10.1016/j.molcel.2019.05.030
205	K Boulias, D Toczydłowska-Socha, BR Hawley, N Liberman, K Takashima, S Zaccara, T Guez, JJ Vasseur, F Debart, L Aravind, SR Jaffrey, EL Greer. Identification of the m6Am methyltransferase PCIF1 reveals the location and functions of m6Am in the transcriptome. Mol Cell 2019; 75(3): 631–643.e8 https://doi.org/10.1016/j.molcel.2019.06.006
206	J Mauer, X Luo, A Blanjoie, X Jiao, AV Grozhik, DP Patil, B Linder, BF Pickering, JJ Vasseur, Q Chen, SS Gross, O Elemento, F Debart, M Kiledjian, SR Jaffrey. Reversible methylation of m6Am in the 5′ cap controls mRNA stability. Nature 2017; 541(7637): 371–375 https://doi.org/10.1038/nature21022
207	S Akichika, S Hirano, Y Shichino, T Suzuki, H Nishimasu, R Ishitani, A Sugita, Y Hirose, S Iwasaki, O Nureki, T Suzuki. Cap-specific terminal N6-methylation of RNA by an RNA polymerase II-associated methyltransferase. Science 2019; 363(6423): eaav0080 https://doi.org/10.1126/science.aav0080
208	S Relier, J Ripoll, H Guillorit, A Amalric, C Achour, F Boissière, J Vialaret, A Attina, F Debart, A Choquet, F Macari, V Marchand, Y Motorin, E Samalin, JJ Vasseur, J Pannequin, F Aguilo, E Lopez-Crapez, C Hirtz, E Rivals, A Bastide, A David. FTO-mediated cytoplasmic m6Am demethylation adjusts stem-like properties in colorectal cancer cell. Nat Commun 2021; 12(1): 1716 https://doi.org/10.1038/s41467-021-21758-4
209	Y Zhao, S Wen, H Li, CW Pan, Y Wei, T Huang, Z Li, Y Yang, S Fan, Y Zhang. Enhancer RNA promotes resistance to radiotherapy in bone-metastatic prostate cancer by m6A modification. Theranostics 2023; 13(2): 596–610 https://doi.org/10.7150/thno.78687
210	W Zhuo, M Sun, K Wang, L Zhang, K Li, D Yi, M Li, Q Sun, X Ma, W Liu, L Teng, C Yi, T Zhou. m6Am methyltransferase PCIF1 is essential for aggressiveness of gastric cancer cells by inhibiting TM9SF1 mRNA translation. Cell Discov 2022; 8(1): 48 https://doi.org/10.1038/s41421-022-00395-1
211	S Gao, J Zhou, Z Hu, S Zhang, Y Wu, PP Musunuru, T Zhang, L Yang, X Luo, J Bai, Q Meng, R Yu. Effects of the m6Am methyltransferase PCIF1 on cell proliferation and survival in gliomas. Biochim Biophys Acta Mol Basis Dis 2022; 1868(11): 166498 https://doi.org/10.1016/j.bbadis.2022.166498
212	L Wang, L Wu, Z Zhu, Q Zhang, W Li, GM Gonzalez, Y Wang, TM Rana. Role of PCIF1-mediated 5′-cap N6-methyladeonsine mRNA methylation in colorectal cancer and anti-PD-1 immunotherapy. EMBO J 2023; 42(2): e111673 https://doi.org/10.15252/embj.2022111673
213	D Arango, D Sturgill, N Alhusaini, AA Dillman, TJ Sweet, G Hanson, M Hosogane, WR Sinclair, KK Nanan, MD Mandler, SD Fox, TT Zengeya, T Andresson, JL Meier, J Coller, S Oberdoerffer. Acetylation of cytidine in mRNA promotes translation efficiency. Cell 2018; 175(7): 1872–1886.e24 https://doi.org/10.1016/j.cell.2018.10.030
214	D Dominissini, G Rechavi. N4-acetylation of cytidine in mRNA by NAT10 regulates stability and translation. Cell 2018; 175(7): 1725–1727 https://doi.org/10.1016/j.cell.2018.11.037
215	X Zheng, Q Wang, Y Zhou, D Zhang, Y Geng, W Hu, C Wu, Y Shi, J Jiang. N-acetyltransferase 10 promotes colon cancer progression by inhibiting ferroptosis through N4-acetylation and stabilization of ferroptosis suppressor protein 1 (FSP1) mRNA. Cancer Commun (Lond) 2022; 42(12): 1347–1366 https://doi.org/10.1002/cac2.12363
216	Y Zhang, Y Jing, Y Wang, J Tang, X Zhu, WL Jin, Y Wang, W Yuan, X Li, X Li. NAT10 promotes gastric cancer metastasis via N4-acetylated COL5A1. Signal Transduct Target Ther 2021; 6(1): 173 https://doi.org/10.1038/s41392-021-00489-4
217	M Deng, L Zhang, W Zheng, J Chen, N Du, M Li, W Chen, Y Huang, N Zeng, Y Song, Y Chen. Helicobacter pylori-induced NAT10 stabilizes MDM2 mRNA via RNA acetylation to facilitate gastric cancer progression. J Exp Clin Cancer Res 2023; 42(1): 9 https://doi.org/10.1186/s13046-022-02586-w
218	G Wang, M Zhang, Y Zhang, Y Xie, J Zou, J Zhong, Z Zheng, X Zhou, Y Zheng, B Chen, C Liu. NAT10-mediated mRNA N4-acetylcytidine modification promotes bladder cancer progression. Clin Transl Med 2022; 12(5): e738 https://doi.org/10.1002/ctm2.738
219	Q Yang, X Lei, J He, Y Peng, Y Zhang, R Ling, C Wu, G Zhang, B Zheng, X Chen, B Zou, Z Fu, L Zhao, H Liu, Y Hu, J Yu, F Li, G Ye, G Li. N4-acetylcytidine drives glycolysis addiction in gastric cancer via NAT10/SEPT9/HIF-1α positive feedback loop. Adv Sci (Weinh) 2023; 10(23): e2300898 https://doi.org/10.1002/advs.202300898

[1]	Hongye Zeng, Wenjing Ning, Xue Liu, Wenxin Luo, Ningshao Xia. Unlocking the potential of bispecific ADCs for targeted cancer therapy[J]. Front. Med., 2024, 18(4): 597-621.
[2]	Yue Ma, Hongwei Lv, Fuxue Xing, Wei Xiang, Zixin Wu, Qiyu Feng, Hongyang Wang, Wen Yang. Cancer stem cell-immune cell crosstalk in the tumor microenvironment for liver cancer progression[J]. Front. Med., 2024, 18(3): 430-445.
[3]	Haoyu Wang, Zhengyuan Wang, Zheng Wang, Xiaoyang Li, Yuntong Li, Ni Yan, Lili Wu, Ying Liang, Jiale Wu, Huaxin Song, Qing Qu, Jiahui Huang, Chunkang Chang, Kunwei Shen, Xiaosong Chen, Min Lu. *Decitabine induces IRF7-mediated immune responses in p53-mutated triple-negative breast cancer: a clinical and translational study*[J]. Front. Med., 2024, 18(2): 357-374.
[4]	Guoqiang Li, Peng Pu, Mengqiao Pan, Xiaoling Weng, Shimei Qiu, Yiming Li, Sk Jahir Abbas, Lu Zou, Ke Liu, Zheng Wang, Ziyu Shao, Lin Jiang, Wenguang Wu, Yun Liu, Rong Shao, Fatao Liu, Yingbin Liu. Topological reorganization and functional alteration of distinct genomic components in gallbladder cancer[J]. Front. Med., 2024, 18(1): 109-127.
[5]	Zhichen Jiang, Xiaohao Zheng, Min Li, Mingyang Liu. Improving the prognosis of pancreatic cancer: insights from epidemiology, genomic alterations, and therapeutic challenges[J]. Front. Med., 2023, 17(6): 1135-1169.
[6]	Pengfei Zhao, Yating Wang, Xiao Yu, Yabing Nan, Shi Liu, Bin Li, Zhumei Cui, Zhihua Liu. Long noncoding RNA LOC646029 functions as a ceRNA to suppress ovarian cancer progression through the miR-627-3p/SPRED1 axis[J]. Front. Med., 2023, 17(5): 924-938.
[7]	Tianzhuo Wang, Huiying Guo, Lei Zhang, Miao Yu, Qianchen Li, Jing Zhang, Yan Tang, Hongquan Zhang, Jun Zhan. FERM domain-containing protein FRMD6 activates the mTOR signaling pathway and promotes lung cancer progression[J]. Front. Med., 2023, 17(4): 714-728.
[8]	Ying Dong, Yingbei Qi, Haowen Jiang, Tian Mi, Yunkai Zhang, Chang Peng, Wanchen Li, Yongmei Zhang, Yubo Zhou, Yi Zang, Jia Li. The development and benefits of metformin in various diseases[J]. Front. Med., 2023, 17(3): 388-431.
[9]	Mingyue Tan, Qi Pan, Qi Wu, Jianfa Li, Jun Wang. Aldolase B attenuates clear cell renal cell carcinoma progression by inhibiting CtBP2[J]. Front. Med., 2023, 17(3): 503-517.
[10]	Yifan Chang, Xianzhi Zhao, Yutian Xiao, Shi Yan, Weidong Xu, Ye Wang, Huojun Zhang, Shancheng Ren. Neoadjuvant radiohormonal therapy for oligo-metastatic prostate cancer: safety and efficacy outcomes from an open-label, dose-escalation, single-center, phase I/II clinical trial[J]. Front. Med., 2023, 17(2): 231-239.
[11]	Xueqing Hu, Ujjwol Khatri, Tao Shen, Jie Wu. Progress and challenges in RET-targeted cancer therapy[J]. Front. Med., 2023, 17(2): 207-219.
[12]	Jia Zhong, Hua Bai, Zhijie Wang, Jianchun Duan, Wei Zhuang, Di Wang, Rui Wan, Jiachen Xu, Kailun Fei, Zixiao Ma, Xue Zhang, Jie Wang. Treatment of advanced non-small cell lung cancer with driver mutations: current applications and future directions[J]. Front. Med., 2023, 17(1): 18-42.
[13]	Danhui Weng, Huihua Xiong, Changkun Zhu, Xiaoyun Wan, Yaxia Chen, Xinyu Wang, Youzhong Zhang, Jie Jiang, Xi Zhang, Qinglei Gao, Gang Chen, Hui Xing, Changyu Wang, Kezhen Li, Yaheng Chen, Yuyan Mao, Dongxiao Hu, Zimin Pan, Qingqin Chen, Baoxia Cui, Kun Song, Cunjian Yi, Guangcai Peng, Xiaobing Han, Ruifang An, Liangsheng Fan, Wei Wang, Tingchuan Xiong, Yile Chen, Zhenzi Tang, Lin Li, Xingsheng Yang, Xiaodong Cheng, Weiguo Lu, Hui Wang, Beihua Kong, Xing Xie, Ding Ma. Adjuvant chemotherapy versus adjuvant concurrent chemoradiotherapy after radical surgery for early-stage cervical cancer: a randomized, non-inferiority, multicenter trial[J]. Front. Med., 2023, 17(1): 93-104.
[14]	Jianhua Shi, Ying Cheng, Qiming Wang, Kai Li, Lin Wu, Baohui Han, Gongyan Chen, Jianxing He, Jie Wang, Haifeng Qin, Xiaoling Li. Anlotinib as third- or further-line therapy for short-term relapsed small-cell lung cancer: subgroup analysis of a randomized phase 2 study (ALTER1202)[J]. Front. Med., 2022, 16(5): 766-772.
[15]	Shi-Yong Sun. Targeting apoptosis to manage acquired resistance to third generation EGFR inhibitors[J]. Front. Med., 2022, 16(5): 701-713.

Viewed

Full text

Abstract

Cited

Shared

Discussed