Table 2.
RBPs involved in RNA modification
| Gene | Protein/RNP function | Target Genes | Biological consequences | Type of cancer | Expression in cancer | Ref |
|---|---|---|---|---|---|---|
| METTL3 | RNA hypermethylation, m6A writer | c-MYC, BCL2, PTEN | promotes oncogenes translation | AML MOLM-13 | upregulation | 20 |
| RNA m6A writer, DNA promoter binding through binding CEBPZ | global | methylation of coding regions of mRNAs, m6A-dependent translation, relieving ribosome stalling | AML | 19 | ||
| Attenuate translation, cytoplasmic localization | WTAP | translation, interaction with eIF3, upregulated expression | K562, HeLa | 23 | ||
| METTL14 | RNA recognition | MYB, MYC | enables m6A methylation by METTL3, regulates self-renewal and differentiation | AML (LSCs) | upregulation | 21 |
| WTAP | RNA recognition | global analysis, transcription and RNA processing genes | promotes m6A methylation by METTL3 enables METTL3 nuclear localization | HEK293 cells, HeLa | upregulation | 24 |
| CD4, CD44, CEBPA, CSF1R, MPO, ABCG2, TCL1A, CYP1A1, CYP3A4, FGFR1, PTPRC (CD45), CD83, CD86, CD9 and CCR4. | abnormal proliferation and arrested differentiastion | AML, HL-60, K562 | 25 | |||
| RBM15 | RNA recognition | genes on the X chromosome | transcriptional silencing by lncRNA XIST | n/a | n/a | 26 |
| FTO | RNA hypomethylation, m6A eraser | NANOG, SOX2 WNT signaling | stem cell genes, oncogenes upregulated | AML: MLLr, PML-RARA, FLT3-ITD, NPM1 mut. | upregulation | 28 |
| ASB2, RARA | differentiation factors are downregulated | |||||
| immune checkpoint genes e.g. LILRB4 | immune evasion | AML (LSCs) | 29 | |||
| U1, U2, U6 snRNAs | demethylation, FTO inhibition leads to altered splicing | human TF-1 erythroleukemia cells | tumor suppressor? | 31 | ||
| ALKBH5 | RNA hypomethylation, m6A eraser | TACC3 | functions as an oncogene in AML regardless of TP53 mutation status; significantly associated with shorter overall survival and poor prognosis in AML, similar to solid tumors | NOMO-1 (TP53-mutant), MV4;11 (TP53-WT) and MA9.3-ITDcells (TP53-WT), in vivo | upregulation | 32 |
| promotes LSCs self-renewal through MYC-p21 axis | AML (LSCs) | |||||
| receptor tyrosine kinase AXL | AXL mRNA stability in m6A-dependent manner; MYB, Pol II activity | AML (LSCs) | 33 | |||
| YTHDF2 | m6A reader, cytoplasmic, targets mRNA for degradation | TNFR2 | Inhibition of apoptosis, enhanced self-renewal | AML (LSCs) | upregulation | 34 |
Abbreviations used: Acute myeloid leukemia (AML); acute promyeloblastic leukemia (APL); acute megakaryoblastic leukemia (AMKL); acute lymphoblastic or lymphocytic (ALL); B-cell acute lymphoblastic leukemia (B-ALL); adult T-cell leukemia/lymphoma (ATL); diffuse large B-cell lymphomas (DLBCLs); chronic myeloid leukemia (CML), chronic phase (CP), accelerated phase (AP), blast crisis (BC); chronic lymphoblastic or lymphocytic leukemia (CLL); myelodysplastic syndromes (MDS); multiple myeloma (MM); hepatocellular carcinoma (HCC); leukemia stem cell (LSC); wild type (WT); patient-derived xenograft (PDX); bone marrow (BM); hematopoietic stem/progenitor cells (HSCs, HSPCs).