TABLE 1.
A summary of known RNA epigenetic modifications and potential targets in HCC.
| Modification type | Modification regulator | Gene name | Mechanism of action | References |
| m6A | METTL3 | FOXO3 mRNA | METTL3 regulates sorafenib resistance in HCC through FOXO3-mediated autophagy | 10.15252/embj.2019103181 |
| METTL3 | SOCS2 mRNA | METTL3 promotes HCC progression through YTHDF2-dependent posttranscriptional silencing of SOCS2 | 10.1002/hep.29683 | |
| METTL3 | LINC00958 | METTL3-mediated upregulation of LINC00958 increases lipogenesis in HCC | 10.1186/s13045-019-0839-x | |
| METTL3 | FEN1 mRNA | METTL3 and IGF2BP2 maintained FEN1 expression through an m6A-IGF2BP2-dependent mechanism in HCC | 10.3389/fonc.2020.578816 | |
| METTL3 | Snail mRNA | SUMO1 modification of METTL3 promotes tumor progression via regulating Snail mRNA homeostasis in HCC | 10.7150/thno.42539 | |
| METTL3 | circ-ARL3 | METTL3 promotes circ-ARL3 to facilitate HBV-associated HCC via sponging miR-1305 | 10.1002/iub.2438 | |
| METTL3 | CD47 mRNA | METTL3/IGF2BP1/CD47 mediated EMTcontributes to the incomplete ablation induced metastasis in HCC cells | 10.1016/j.bbrc.2021.01.085 | |
| METTL3 | RDM1 mRNA | METTL3 represses RDM1 to increase cell proliferation, colony formation in HCC | 10.1002/1878-0261.12593 | |
| METTL3 | lncRNA NIFK-AS1 | METTL3 upregulates lncRNA NIFK-AS1 to promotes HCC progression and sorafenib resistance | 10.1007/s13577-021-00587-z | |
| METTL3 | LncRNA MEG3 | METTL3-induced LncRNA MEG3 to suppress the proliferation, migration and invasion of HCC through miR-544b/BTG2 signaling | 10.2147/OTT.S289198 | |
| METTL14 | EGFR mRNA | METTL14 inhibits HCC Metastasis through regulating EGFR/PI3K/Akt signaling | 10.2147/CMAR.S286275 | |
| METTL14 | HNF3γ mRNA | METTL14-mediated HNF3γ reduction renders HCC dedifferentiation and sorafenib resistance | 10.1038/s41392-020-00299-0 | |
| METTL14 | USP48 mRNA | METTL14 upregulates USP48 to attenuate HCC via regulating SIRT6 stabilization | 10.1158/0008-5472.CAN-20-4163 | |
| WTAP | ETS1 mRNA | WTAP facilitates progression of HCC via m6A-HuR-dependent epigenetic silencing of ETS1 | 10.1186/s12943-019-1053-8 | |
| VIRMA | GATA3 mRNA | VIRMA contributes to HCC progression through m6A-dependent post-transcriptional modification of GATA3 | 10.1186/s12943-019-1106-z | |
| FTO | CUL4A mRNA | FTO reduces CUL4A abundance to reverse the increased hepatocyte proliferation in HCC | 10.1016/j.molmet.2020.101085 | |
| FTO | PKM2 mRNA | FTO promotes HCC tumorigenesis via mediating PKM2 demethylation | PMID: 31632576; PMID: PMC6789218 | |
| FTO | GNAO1 mRNA | SIRT1 destabilizes FTO to steering the GNAO1 mRNA expression in HCC tumorigenesis | 10.1002/hep.31222 | |
| ALKBH5 | LYPD1 mRNA | ALKBH5 suppresses malignancy of HCC via m6A-guided epigenetic inhibition of LYPD1 | 10.1186/s12943-020-01239-w | |
| ALKBH5 | HBx mRNA | ALKBH5 catalyzes HBx mRNA to promote HBV-driven HCC cells’ growth and migration | 10.1186/s12885-021-08449-5 | |
| YTHDF1 | ATG2A and ATG14 mRNA | YTHDF1 drives hypoxia-induced autophagy and malignancy of HCC by promoting ATG2A and ATG14 translation | 10.1038/s41392-020-00453-8 | |
| YTHDF1 | Akt mRNA | YTHDF1 promotes HCC progression via activating PI3K/AKT/mTOR signaling and inducing EMT | 10.1186/s40164-021-00227-0 | |
| YTHDF1 | FZD5 mRNA | YTHDF1 facilitates the progression of HCC by promoting FZD5 mRNA translation | 10.1016/j.omtn.2020.09.036 | |
| YTHDF1 | Akt mRNA | YTHDF1 promote the HCC cell aggressive phenotypes by facilitating EMT and activating Akt/glycogen GSK-3β/β-catenin signaling | 10.3389/fmolb.2020.60476 | |
| YTHDF2 | IL11 and SERPINE2 mRNA | YTHDF2 processed the decay of IL11 and SERPINE2 mRNAs responsible for the inflammation-mediated malignancy and disruption of vascular normalization in HCC | 10.1186/s12943-019-1082-3 | |
| YTHDF2 | OCT4 mRNA | YTHDF2 promotes the liver cancer stem cell phenotype and cancer metastasis by regulating OCT4 expression | 10.1038/s41388-020-1303-7 | |
| YTHDF2 | EGFR mRNA | YTHDF2 suppresses cell proliferation and growth via destabilizing the EGFR mRNA in HCC | 10.1016/j.canlet.2018.11.006 | |
| YTHDF3 | Zeb1 mRNA | circ_KIAA1429 accelerates HCC advancement through m6A-YTHDF3-Zeb1 | 10.1016/j.lfs.2020.118082 | |
| YTHDF3 | ITGA6 mRNA | KDM5B promotes self-renewal of HCC cells through the microRNA-448-mediated YTHDF3/ITGA6 axis | 10.1111/jcmm.16342 | |
| m5C | NSUN2 | H19 lncRNA | Aberrant NSUN2-mediated m(5)C modification of H19 lncRNA is associated with poor differentiation of HCC | 10.1038/s41388-020-01475-w |
| NSUN2 | FZR1 mRNA | NSUN2 promotes growth of HCC cells by regulating FZR1 in vitro and in vivo | 10.1002/kjm2.12430 | |
| TET1/TET2 | SOCS1 mRNA | miR-29a down-regulates anti-metastatic SOCS1 by directly targeting the TET family | 10.1007/s12032-014-0291-2 | |
| m7G | METTL1 | PTEN mRNA | METTL1 overexpression is correlated with poor prognosis and promotes HCC via PTEN | 10.1007/s00109-019-01830-9 |
| WDR4 | CCNB1 mRNA | WDR4 promotes proliferation, metastasis, and sorafenib resistance by inducing CCNB1 translation in HCC | 10.1038/s41419-021-03973-5 | |
| Pseudouridine | Unknown | 18S rRNA component of the small (40S) ribosomal subunit | snoRNA24 guided pseudouridine modifications increased translational miscoding and stop codon readthrough frequencies in HCC | 10.7554/eLife.48847 |
ALKBH5, AlkB homolog 5; ATG2A, Autophagy related 2a; BTG2, B cell translocation gene 2; CCNB1, cyclin B1; CUL4A, Cullin 4A; EGFR, Epidermal growth factor receptor; EMT, Epithelial-to-mesenchymal transition; ETS1, ETS proto-oncogene 1; FEN1, Flap endonuclease-1; FOXO3, Forkhead transcription factor 3; FTO, Fat mass and obesity-related protein; FZD5, Frizzled homolog 5; FZR1, Fizzy-related-1; GATA3, GATA binding protein 3; GNAO1, Guanine nucleotide-binding protein, α-activating activity polypeptide O; HBV, Hepatitis B virus; HBx, HBV derived X protein; HCC, hepatocellular carcinoma; HNF3γ, Hepatocyte nuclear factor 3γ; IGF2BP1, Insulin-like growth factor 2 mRNA binding protein 1; IL11, Interleukin 11; ITGA6, integrin subunit alpha 6; KDM5B, Lysine-specific demethylase 5B; LYPD1, LY6/PLAUR domain containing 1; m5C, 5-methylcytosine; m6A, N6-methyladenosine; m7G, N7-methylguanosine; METTL14, Methyltransferase-like 14; METTL3, Methyltransferase-like 3; NSUN2, NOP2/Sun domain family, member 2; OCT4, Octamer-binding transcription factor 4; PKM2, Pyruvate kinase type M2; PTEN, Phosphatase and tensin homolog; RDM1, RAD52 motif 1; SERPINE2, Serpin family E member 2; SIRT1/6, Silent information regulator 1/6; SNORA24, Small nucleolar RNA 24; SOCS1/2, Suppressor of cytokine signaling 1/2; SUMO1, Small ubiquitin-like modifier; TET1/TET2, Ten-eleven translocation methyl-cytosine dioxygenase 1/2; USP48, Ubiquitin-specific peptidase 48; VIRMA, Vir-like m6A methyltransferase with association; WDR4, WD repeat domain 4; WTAP, Wilms tumor 1-associating protein 1.