Deciphering the Divergent Gene Expression Landscapes of m6A/m5C/m1A Methylation Regulators in Hepatocellular Carcinoma Through Single-Cell and Bulk RNA Transcriptomic Analysis

References

• Llovet JM, Kelley RK, Villanueva A, et al. Hepatocellular carcinoma. Nat Rev Dis Primers. 2021;7(1):6. doi:10.1038/s41572-020-00240-3
   PubMed Web of Science ®Google Scholar
• Boulias K, Greer EL. Biological roles of adenine methylation in RNA. Nat Rev Genet. 2023;24:143–160. doi:10.1038/s41576-022-00534-0
   PubMed Web of Science ®Google Scholar
• Patrasso EA, Raikundalia S, Arango D. Regulation of the epigenome through RNA modifications. Chromosoma. 2023;132:231–246. doi:10.1007/s00412-023-00794-7
   PubMed Web of Science ®Google Scholar
• Su T, Liu J, Zhang N, et al. New insights on the interplays between m(6)A modifications and microRNA or lncRNA in gastrointestinal cancers. Front Cell Dev Biol. 2023;11:1157797. doi:10.3389/fcell.2023.1157797
   PubMed Web of Science ®Google Scholar
• Tang Q, Li L, Wang Y, et al. RNA modifications in cancer. Br J Cancer. 2023;129:204–221. doi:10.1038/s41416-023-02275-1
   PubMed Web of Science ®Google Scholar
• Wang Z, Zhou J, Zhang H, Ge L, Li J, Wang H. RNA m(6) A methylation in cancer. Mol Oncol. 2023;17:195–229. doi:10.1002/1878-0261.13326
   PubMed Web of Science ®Google Scholar
• Wei Y, Li Y, Lu C. Exploring the role of m6A modification in cancer. Proteomics. 2023;23:e2200208. doi:10.1002/pmic.202200208
   PubMed Web of Science ®Google Scholar
• Zhuang H, Yu B, Tao D, et al. The role of m6A methylation in therapy resistance in cancer. Mol Cancer. 2023;22:91. doi:10.1186/s12943-023-01782-2
   PubMed Web of Science ®Google Scholar
• Braghini MR, Lo Re O, Romito I, et al. Epigenetic remodelling in human hepatocellular carcinoma. J Exp Clin Cancer Res. 2022;41:107. doi:10.1186/s13046-022-02297-2
   PubMed Web of Science ®Google Scholar
• Wang S, Gao S, Ye W, Li Y, Luan J, Lv X. The emerging importance role of m6A modification in liver disease. Biomed Pharmacother. 2023;162:114669. doi:10.1016/j.biopha.2023.114669
   PubMed Web of Science ®Google Scholar
• Wang Y, Zeng J, Chen W, Fan J, Hylemon PB, Zhou H. Long noncoding RNA H19: a novel oncogene in liver cancer. Noncoding RNA. 2023;9. doi:10.3390/ncrna9020019
   Web of Science ®Google Scholar
• Xu K, Wu T, Xia P, Chen X, Yuan Y. Alternative splicing: a bridge connecting NAFLD and HCC. Trends Mol Med. 2023. doi:10.1016/j.molmed.2023.07.001
   Web of Science ®Google Scholar
• Yang L, Tian S, Zheng X, et al. N6-methyladenosine RNA methylation in liver diseases: from mechanism to treatment. J Gastroenterol. 2023;58:718–733. doi:10.1007/s00535-023-02008-4
   PubMed Web of Science ®Google Scholar
• Mao Y, Ding Z, Jiang M, Yuan B, Zhang Y, Zhang X. Circ_0091579 exerts an oncogenic role in hepatocellular carcinoma via mediating miR-136-5p/TRIM27. Biomed J. 2022;45:883–895. doi:10.1016/j.bj.2021.12.009
   PubMed Web of Science ®Google Scholar
• Yu MC, Wu TH, Lee CW, et al. Percentage genome change and chromosome 7q amplification predict sorafenib response in advanced hepatocellular carcinoma. Biomed J. 2021;44:S73–S83. doi:10.1016/j.bj.2020.07.001
   PubMed Web of Science ®Google Scholar
• Dominissini D, Moshitch-Moshkovitz S, Schwartz S, et al. Topology of the human and mouse m6A RNA methylomes revealed by m6A-seq. Nature. 2012;485:201–206. doi:10.1038/nature11112
   PubMed Web of Science ®Google Scholar
• Meyer KD, Saletore Y, Zumbo P, Elemento O, Mason CE, Jaffrey SR. Comprehensive analysis of mRNA methylation reveals enrichment in 3’ UTRs and near stop codons. Cell. 2012;149:1635–1646. doi:10.1016/j.cell.2012.05.003
   PubMed Web of Science ®Google Scholar
• Huang J, Yin P. Structural insights into N(6)-methyladenosine (m(6)A) modification in the transcriptome. Genomics Proteomics Bioinf. 2018;16:85–98. doi:10.1016/j.gpb.2018.03.001
   PubMed Web of Science ®Google Scholar
• Yu F, Wei J, Cui X, et al. Post-translational modification of RNA m6A demethylase ALKBH5 regulates ROS-induced DNA damage response. Nucleic Acids Res. 2021;49:5779–5797. doi:10.1093/nar/gkab415
   PubMed Web of Science ®Google Scholar
• Huber SM, van Delft P, Mendil L, et al. Formation and abundance of 5-hydroxymethylcytosine in RNA. Chembiochem. 2015;16:752–755. doi:10.1002/cbic.201500013
   PubMed Web of Science ®Google Scholar
• Legrand C, Tuorto F, Hartmann M, et al. Statistically robust methylation calling for whole-transcriptome bisulfite sequencing reveals distinct methylation patterns for mouse RNAs. Genome Res. 2017;27:1589–1596. doi:10.1101/gr.210666.116
   PubMed Web of Science ®Google Scholar
• Li X, Xiong X, Zhang M, et al. Base-resolution mapping reveals distinct m(1)A methylome in nuclear- and mitochondrial-encoded transcripts. Mol Cell. 2017;68:993–1005.e1009. doi:10.1016/j.molcel.2017.10.019
   PubMed Web of Science ®Google Scholar
• Cusenza VY, Tameni A, Neri A, Frazzi R. The lncRNA epigenetics: the significance of m6A and m5C lncRNA modifications in cancer. Front Oncol. 2023;13:1063636. doi:10.3389/fonc.2023.1063636
   PubMed Web of Science ®Google Scholar
• Gu X, Ma X, Chen C, et al. Vital roles of m(5)C RNA modification in cancer and immune cell biology. Front Immunol. 2023;14:1207371. doi:10.3389/fimmu.2023.1207371
   PubMedGoogle Scholar
• Li M, Tao Z, Zhao Y, et al. 5-methylcytosine RNA methyltransferases and their potential roles in cancer. J Transl Med. 2022;20:214. doi:10.1186/s12967-022-03427-2
   PubMed Web of Science ®Google Scholar
• Song H, Zhang J, Liu B, et al. Biological roles of RNA m(5)C modification and its implications in Cancer immunotherapy. Biomark Res. 2022;10:15. doi:10.1186/s40364-022-00362-8
   PubMed Web of Science ®Google Scholar
• Yu G, Bao J, Zhan M, et al. Comprehensive analysis of m5C methylation regulatory genes and tumor microenvironment in prostate cancer. Front Immunol. 2022;13:914577. doi:10.3389/fimmu.2022.914577
   PubMed Web of Science ®Google Scholar
• Jin H, Huo C, Zhou T, Xie S. m(1)A RNA modification in gene expression regulation. Genes. 2022;13. doi:10.3390/genes13050910
   Web of Science ®Google Scholar
• Li J, Zhang H, Wang H. N(1)-methyladenosine modification in cancer biology: current status and future perspectives. Comput Struct Biotechnol J. 2022;20:6578–6585. doi:10.1016/j.csbj.2022.11.045
   PubMed Web of Science ®Google Scholar
• Song P, Tayier S, Cai Z, Jia G. RNA methylation in mammalian development and cancer. Cell Biol Toxicol. 2021;37:811–831. doi:10.1007/s10565-021-09627-8
   PubMed Web of Science ®Google Scholar
• Li D, Li K, Zhang W, et al. The m6A/m5C/m1A regulated gene signature predicts the prognosis and correlates with the immune status of hepatocellular carcinoma. Front Immunol. 2022;13:918140. doi:10.3389/fimmu.2022.918140
   PubMed Web of Science ®Google Scholar
• Liu T, Sun L, Li ZZ, et al. The m6A/m5C/m1A regulator genes signature reveals the prognosis and is related with immune microenvironment for hepatocellular carcinoma. BMC Gastroenterol. 2023;23:147. doi:10.1186/s12876-023-02776-6
   PubMed Web of Science ®Google Scholar
• Liu Y, Zhu J, Ding L. Involvement of RNA methylation modification patterns mediated by m7G, m6A, m5C and m1A regulators in immune microenvironment regulation of Sjögren’s syndrome. Cell Signal. 2023;106:110650. doi:10.1016/j.cellsig.2023.110650
   PubMed Web of Science ®Google Scholar
• Mao S, Chen Z, Wu Y, Xiong H, Yuan X. Crosstalk of Eight types of RNA modification regulators defines tumor microenvironments, cancer hallmarks, and prognosis of lung adenocarcinoma. J Oncol. 2022;2022:1285632. doi:10.1155/2022/1285632
   PubMed Web of Science ®Google Scholar
• Qi L, Zhang W, Ren X, et al. Cross-Talk of multiple types of RNA modification regulators uncovers the tumor microenvironment and immune infiltrates in soft tissue sarcoma. Front Immunol. 2022;13:921223. doi:10.3389/fimmu.2022.921223
   PubMed Web of Science ®Google Scholar
• Wang Y, Mao Y, Wang C, et al. RNA methylation-related genes of m6A, m5C, and m1A predict prognosis and immunotherapy response in cervical cancer. Ann Med. 2023;55:2190618. doi:10.1080/07853890.2023.2190618
   PubMed Web of Science ®Google Scholar
• Wu ZY, Shi ZY. The prognostic value and immune landscapes of m1A/m5C/m6A-associated lncRNA signature in osteosarcoma. Eur Rev Med Pharmacol Sci. 2022;26:5868–5883. doi:10.26355/eurrev_202208_29526
   PubMed Web of Science ®Google Scholar
• Zhao K, Li W, Yang Y, et al. Comprehensive analysis of m(6)A/m(5)C/m(1)A-related gene expression, immune infiltration, and sensitivity of antineoplastic drugs in glioma. Front Immunol. 2022;13:955848. doi:10.3389/fimmu.2022.955848
   PubMed Web of Science ®Google Scholar
• Kong Y, Yu J, Ge S, Fan X. Novel insight into RNA modifications in tumor immunity: promising targets to prevent tumor immune escape. Innovation. 2023;4:100452. doi:10.1016/j.xinn.2023.100452
   Google Scholar
• Yang Z, Zhang S, Xia T, et al. RNA modifications meet tumors. Cancer Manag Res. 2022;14:3223–3243. doi:10.2147/cmar.S391067
   PubMed Web of Science ®Google Scholar
• Biswas S, Rao CM. Epigenetic tools (The Writers, The Readers and The Erasers) and their implications in cancer therapy. Eur J Pharmacol. 2018;837:8–24. doi:10.1016/j.ejphar.2018.08.021
   PubMed Web of Science ®Google Scholar
• Li X, Xiong X, Wang K, et al. Transcriptome-wide mapping reveals reversible and dynamic N(1)-methyladenosine methylome. Nat Chem Biol. 2016;12:311–316. doi:10.1038/nchembio.2040
   PubMed Web of Science ®Google Scholar
• Zhang Q, Liu F, Chen W, et al. The role of RNA m(5)C modification in cancer metastasis. Int J Biol Sci. 2021;17:3369–3380. doi:10.7150/ijbs.61439
   PubMed Web of Science ®Google Scholar
• He L, Li H, Wu A, Peng Y, Shu G, Yin G. Functions of N6-methyladenosine and its role in cancer. Mol Cancer. 2019;18:176. doi:10.1186/s12943-019-1109-9
   PubMed Web of Science ®Google Scholar
• Li T, Fu J, Zeng Z, et al. TIMER2.0 for analysis of tumor-infiltrating immune cells. Nucleic Acids Res. 2020;48:W509–W514. doi:10.1093/nar/gkaa407
   PubMed Web of Science ®Google Scholar
• Sun GF, Ding H. NOP2-mediated m5C methylation of XPD is associated with hepatocellular carcinoma progression. Neoplasma. 2023;70:340–349. doi:10.4149/neo_2023_230110N17
   PubMed Web of Science ®Google Scholar
• Zhang XW, Wu LY, Liu HR, et al. NSUN5 promotes progression and predicts poor prognosis in hepatocellular carcinoma. Oncol Lett. 2022;24:439. doi:10.3892/ol.2022.13559
   PubMed Web of Science ®Google Scholar
• Wang Y, Wang J, Li X, et al. N(1)-methyladenosine methylation in tRNA drives liver tumourigenesis by regulating cholesterol metabolism. Nat Commun. 2021;12:6314. doi:10.1038/s41467-021-26718-6
   PubMed Web of Science ®Google Scholar
• Ye Y, Liu M, Wu F, et al. TRMT6 promotes hepatocellular carcinoma progression through the PI3K/AKT signaling pathway. Eur J Med Res. 2023;28:48. doi:10.1186/s40001-022-00951-1
   PubMed Web of Science ®Google Scholar
• Wang Y, Huang Q, Deng T, Li BH, Ren XQ. Clinical significance of TRMT6 in hepatocellular carcinoma: a bioinformatics-based study. Med Sci Monit. 2019;25:3894–3901. doi:10.12659/msm.913556
   PubMed Web of Science ®Google Scholar
• Zhao Q, Zhang Y, Shao S, Sun Y, Lin Z. Identification of hub genes and biological pathways in hepatocellular carcinoma by integrated bioinformatics analysis. PeerJ. 2021;9:e10594. doi:10.7717/peerj.10594
   PubMed Web of Science ®Google Scholar
• Elcheva IA, Gowda CP, Bogush D, et al. IGF2BP family of RNA-binding proteins regulate innate and adaptive immune responses in cancer cells and tumor microenvironment. Front Immunol. 2023;14:1224516. doi:10.3389/fimmu.2023.1224516
   PubMedGoogle Scholar
• Shao W, Zhao H, Zhang S, et al. A pan-cancer landscape of IGF2BPs and their association with prognosis, stemness and tumor immune microenvironment. Front Oncol. 2022;12:1049183. doi:10.3389/fonc.2022.1049183
   PubMed Web of Science ®Google Scholar
• Ramesh-Kumar D, Guil S. The IGF2BP family of RNA binding proteins links epitranscriptomics to cancer. Semin Cancer Biol. 2022;86:18–31. doi:10.1016/j.semcancer.2022.05.009
   PubMed Web of Science ®Google Scholar
• Zhu TY, Hong LL, Ling ZQ. Oncofetal protein IGF2BPs in human cancer: functions, mechanisms and therapeutic potential. Biomark Res. 2023;11:62. doi:10.1186/s40364-023-00499-0
   PubMed Web of Science ®Google Scholar
• Yang J, Qin T, Liu S, Tang H, Liu M, Wang Q. Interaction analysis of miR-1275/IGF2BP1/IGF2BP3 with the susceptibility to hepatocellular carcinoma. Biomarker Med. 2020;14:283–292. doi:10.2217/bmm-2019-0332
   PubMed Web of Science ®Google Scholar
• Liang Y, Chen S, Xie J, et al. Establishment of a prognostic model based on m(6)A regulatory factors and stemness of hepatocellular carcinoma using RNA-seq data and scRNA-seq data. J Cancer Res Clin Oncol. 2023. doi:10.1007/s00432-023-05045-x
   Web of Science ®Google Scholar
• Czepukojc B, Abuhaliema A, Barghash A, et al. IGF2 mRNA binding protein 2 transgenic mice are more prone to develop a ductular reaction and to progress toward cirrhosis. Front Med. 2019;6:179. doi:10.3389/fmed.2019.00179
   Web of Science ®Google Scholar
• Waly AA, El-Ekiaby N, Assal RA, et al. Methylation in MIRLET7A3 gene induces the expression of IGF-II and its mRNA binding proteins IGF2BP-2 and 3 in hepatocellular carcinoma. Front Physiol. 2018;9:1918. doi:10.3389/fphys.2018.01918
   PubMed Web of Science ®Google Scholar
• Fawzy IO, Hamza MT, Hosny KA, Esmat G, Abdelaziz AI. Abrogating the interplay between IGF2BP1, 2 and 3 and IGF1R by let-7i arrests hepatocellular carcinoma growth. Growth Factors. 2016;34:42–50. doi:10.3109/08977194.2016.1169532
   PubMed Web of Science ®Google Scholar