Site-specific RNA editing events in hematologic malignancies
| Disease . | Gene . | Editing sites . | Mechanisms . | Outcomes . | References . |
|---|---|---|---|---|---|
| AML | PTPN6 | Intron | Create aberrant splicing isoform | Nonfunctional PTPN6 dysregulates its suppressor function on cKit signaling | 33,114,115 |
| AML | STAT3 | Intron | Affect alternative splicing and increase a shorter form STAT3β | Promote transformation of pre-LSCs into LSCs that drive therapy-resistant sAML transformation | 35,117 |
| AML | COPA | CDS | I164V | Inhibit the colony-forming of t(8:21) AML cells | 31 |
| COG3 | CDS | I635V | |||
| AML | SOCS2-AS1 | LncRNA | Not stated | Correlated with low mRNA abundance and poor prognosis | 120 |
| AML | Pri-miR-142 | Drosha cleavage site | Edited pri-miRNA was degraded by Tudor-SN | Inhibit mature miR-142 biogenesis | 48 |
| CML | Pri-let-7 | DROSHA and DICER cleavage sites | Upregulate LIN28B | Promote LSC proliferation | 50 |
| CML | Pri-miR-26a | DROSHA cleavage site | Inhibit maturation of miR-26a | Upregulate miR-26a target transcripts, which activates cell cycle–related gene CDKN1A | 37 |
| CML | MDM2 | 3′UTR | Prevents miR-155 binding | Increase MDM2 expression and repress the p53 tumor suppressor | 37,38 |
| CML | GSK3β | Intron | Increase a novel in-frame splice deletion | Increase β-catenin expression and serial leukemia engraftment potential | 79,121 |
| CLL | miR-184, miR-589, miR-6503, miR3157 | miRNAs | Deregulate mRNA target network | Affect the pathogenesis of CLL | 129 |
| CLL | COG3, CDK13, FLNB, BLCAP | Nonsynonymous | Protein recoding | Probably contribute to treatment sensitivity in CLL | 23 |
| T-ALL | MAVS, IL17RA | 3′UTR | Not stated | Low editing events are probably associated with loss of LIC stemness | 130 |
| MYB | Intron | Not stated | |||
| DLBCL | PRDM1 | Exon-intron junction | Premature translation termination | PRDM1 inactivation and inhibition of terminal differentiation in DLBCL | 34 |
| DLBCL | MAVS | 3′ UTR | Increase MAVS protein expression levels | Increase inflammation cascade and T-cell exhaustion | 133 |
| PEL | pri-miRNA-K12-4 | Stem region and seed region | Regulate miRNA biogenesis and target specificity | Regulate viral life cycle of KSHV | 134 |
| MM | GLI1 | Exon | R701G, increase GLI1 transcriptional activity and decrease SUFU binding | Activate Hedgehog pathway and lead to therapeutic resistance | 32 |
| MM | NEIL1 | Exon | K242R, change the lesion specificity of NEIL1 | Display ineffective oxidative damage repair capacity and loss-of-TSG function properties | 137 |
| MM | MDM4, EIF2AK2 | 3′ UTR | Interact with p53 and NF-κB | Promote MM progression | 142 |
| Disease . | Gene . | Editing sites . | Mechanisms . | Outcomes . | References . |
|---|---|---|---|---|---|
| AML | PTPN6 | Intron | Create aberrant splicing isoform | Nonfunctional PTPN6 dysregulates its suppressor function on cKit signaling | 33,114,115 |
| AML | STAT3 | Intron | Affect alternative splicing and increase a shorter form STAT3β | Promote transformation of pre-LSCs into LSCs that drive therapy-resistant sAML transformation | 35,117 |
| AML | COPA | CDS | I164V | Inhibit the colony-forming of t(8:21) AML cells | 31 |
| COG3 | CDS | I635V | |||
| AML | SOCS2-AS1 | LncRNA | Not stated | Correlated with low mRNA abundance and poor prognosis | 120 |
| AML | Pri-miR-142 | Drosha cleavage site | Edited pri-miRNA was degraded by Tudor-SN | Inhibit mature miR-142 biogenesis | 48 |
| CML | Pri-let-7 | DROSHA and DICER cleavage sites | Upregulate LIN28B | Promote LSC proliferation | 50 |
| CML | Pri-miR-26a | DROSHA cleavage site | Inhibit maturation of miR-26a | Upregulate miR-26a target transcripts, which activates cell cycle–related gene CDKN1A | 37 |
| CML | MDM2 | 3′UTR | Prevents miR-155 binding | Increase MDM2 expression and repress the p53 tumor suppressor | 37,38 |
| CML | GSK3β | Intron | Increase a novel in-frame splice deletion | Increase β-catenin expression and serial leukemia engraftment potential | 79,121 |
| CLL | miR-184, miR-589, miR-6503, miR3157 | miRNAs | Deregulate mRNA target network | Affect the pathogenesis of CLL | 129 |
| CLL | COG3, CDK13, FLNB, BLCAP | Nonsynonymous | Protein recoding | Probably contribute to treatment sensitivity in CLL | 23 |
| T-ALL | MAVS, IL17RA | 3′UTR | Not stated | Low editing events are probably associated with loss of LIC stemness | 130 |
| MYB | Intron | Not stated | |||
| DLBCL | PRDM1 | Exon-intron junction | Premature translation termination | PRDM1 inactivation and inhibition of terminal differentiation in DLBCL | 34 |
| DLBCL | MAVS | 3′ UTR | Increase MAVS protein expression levels | Increase inflammation cascade and T-cell exhaustion | 133 |
| PEL | pri-miRNA-K12-4 | Stem region and seed region | Regulate miRNA biogenesis and target specificity | Regulate viral life cycle of KSHV | 134 |
| MM | GLI1 | Exon | R701G, increase GLI1 transcriptional activity and decrease SUFU binding | Activate Hedgehog pathway and lead to therapeutic resistance | 32 |
| MM | NEIL1 | Exon | K242R, change the lesion specificity of NEIL1 | Display ineffective oxidative damage repair capacity and loss-of-TSG function properties | 137 |
| MM | MDM4, EIF2AK2 | 3′ UTR | Interact with p53 and NF-κB | Promote MM progression | 142 |
CDS, coding sequence; Drosha, mouse protein; DROSHA, human protein; LIC, leukemia-initiating cells; lncRNA, long noncoding RNA; PEL, primary effusion lymphoma; sAML, secondary acute myeloid leukemia; TSG, tumor suppressor gene.