Table 1.
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Summary of the function and downstream targets of A-to-I modification in cancer.

Cancer typesA-to-I modifierA-to-I editing siteImpact on mRNA/proteinGene(s) involvedFunctional implicationsOrganisms
A-to-I promoting cancer
Acute lymphoblastic leukemiaADAR1SNPThe variations are expected to disrupt or enhance interaction with other transcriptional regulatory proteinsrs9616 and rs2229857 genetic variantsThe variant at rs9616 and rs2229857 modulates ADAR1 expression and confers a predisposition and relapse risk to ALLHumans/cell lines
Breast cancerADAR1MiRNA, 3ʹUTRRNA editing stabilizes DHFR mRNAmiR-25-3p and miR-125a-3p, DHFRDHFR is posttranscriptionally regulated through ADAR1-mediated RNA editing by editing the miR-25-3p and miR-125a-3p binding sites in the 3’-UTR of DHFR, affecting cell proliferation and sensitivity of BC cells to methotrexateHumans/cell lines
ADAR1MiRNA, 3ʹUTRIncreases METTL3 mRNA and protein levelsMETTL3ADAR1 edits METTL3 mRNA and changes its binding site to miR532-5p, leading to increased METTL3 protein, which further targets ARHGAP5, recognized by YTHDF1 to promote the proliferation, migration, and invasion of BC cellsHumans/cell lines/mice
ADAR1LncRNAAlters LINC00944 expression levels by means of noncanonical functionsLINC00944Edited lncRNA LINC00944 is immune-related and positively correlates to tumor infiltrating T lymphocytes, the age at diagnosis, tumor size, and poor prognosisHumans/cell lines
ADAR1LncRNALINC00624
promotes ADAR1 RNA editing ability by regulating
ADAR1 expression		LINC00624Edited LINC00624 inhibits MHC class I antigen presentation and limits CD8 + Tcell infiltration in the BC microenvironmentHumans/cell lines/mice
ADAR1NANAKYNUEdited KYNU is associated with aggressiveness of BCHumans/cell lines
ADAR1Coding genep.M2293V. The editing reduces FLNB activity via disruption of binding partners
and consequently of localization		FLNB, miR-27a-5p and miR-4485-3pEdited FLNB reduces the tumor suppressive activities of the protein, thereby promoting growth and invasion in TNBC. ADAR1-downregulated miRNAs 27a-5p and miR-4485-3p inhibit cell-cycle progression, and that miR-27a-5p also suppresses invasion and promotes IL6/TNF expression in TNBC cellsCell lines
Cervical cancerADAR1Coding geneY/C, Q/RBLCAPEdited BLCAP regulates the STAT3 signaling pathway to promote the progression of CC carcinogenesisHumans/cell lines
Chronic myeloid leukemiaADAR1IntronADAR1 drives alternative splicing of GSK3βGSK3βADAR1 induces mis-splicing of GSK3β resulting in the renewal of leukemia stem cellHumans/cell lines/mice
ADAR1MiRNAA-to-G nucleotide changes at + 3 and + 59 editing sites may alter RNA secondary structures at DROSHA/DGCR8 and DICER cleavage sitesLet-7ADAR1 reduces let-7 levels and enhances leukemic stem cell renewalHumans/cell lines/mice
ADAR1MiRNAADAR1 hinders pri-miR-26a biogenesis by preventing
DROSHA cleavage		miR-26aADAR1 reduces the maturation of miR-26a, which indirectly represses CDKN1A expression via EZH2, hence regulating cell-cycle transitHumans/cell lines/mice
ADAR13ʹUTRADAR1 reduces miR-155 expressionMDM2ADAR1 edits the 3ʹUTR of MDM2 to prevent targeting by miR-155, leading to increase MDM2 levels and inhibit the activation of p53, thereby promoting the progression of CMLHumans/cell lines/mice
Colorectal cancerADAR1Coding geneS/GAZIN1Edited AZIN1 enhances stemness and appears to drive the metastatic processHumans/cell lines/mice
ADAR2Coding geneQ/R in the fifth amino acid of the BLCAP proteinBLCAPEdited BLCAP facilitates the transition from G1 to S phase of the cell cycle through the loss of repressive effect on Rb1, leading to the increased cell proliferation and reduced apoptosisHumans/cell lines/mice
ADAR13ʹ-UTRIncreases the RNA stabilityPVRADAR-mediated RNA editing may enhance tumor- and immune-related gene activities and pathways in CRC by upregulating PVR expression.Human/cell lines
ADAR1Coding geneS/GAZIN1Edited AZIN1 enhances the invasive potential of CAFs within the TMEHumans/cell lines
Esophageal squamous cell carcinomaADAR1Coding genep.S367GAZIN1Edited AZIN1 transcript is more abundant in tumors, resulting in “gain of function” phenotypes during ESCC progressionHumans/cell lines/mice
ADAR1NANASOX2Oncogenic Sox2 activates endogenous retroviruses, inducing expression of dsRNA and dependence on the ADAR1Human/cell lines/mice
ADAR2Coding gene (c.261A > G)p.N72DSLC22A3Deregulation of SLC22A3 facilitates cell invasion and filopodia formation by reducing its direct association with ACTN4, leading to the increased actin-binding activity of ACTN4 in normal esophageal cellsHumans/cell lines/mice
Gastric cancerADAR1NANAmTORADAR1 activates mTOR/p70S6K/S6 ribosomal protein signaling axis to regulate protein translation, cell proliferation, and autophagyHumans/cell lines/mice
ADAR1MiRNAADAR1 mediates its effect via the interaction with DROSHA or by regulating the transcription of miR-302/367 clustermiR-302a-3p and IRF9ADAR1 regulates IFN signaling through the suppression of STAT1 and IRF9 via miR-302aCell lines
ADAR13′UTRA-to-I editing on 3′UTR of
SCD1 enhances binding of KHDRBS1, thereby increasing SCD1 mRNA stability		SCD1ADAR1/SCD1 axis governs chemoresistance by enhancing lipid droplet formation to neutralize ER stress induced by chemotherapyHumans/cell lines/mice
ADAR1CircRNAADAR1 has the ability to reduce the abundance of hsa_circ_0004872 in GC cellshsa_circ_0004872 and miR-224ADAR1 inhibits the expression of hsa_circ_0004872, which led to the upregulation of miR-224. Smad4, the target of miR-224, could further influence hsa_circ_0004872 levels by binding directly to the promoter region of ADAR1 to inhibit ADAR1 expressionHumans/cell lines/mice
GlioblastomaADAR1NAADAR1 binds and stabilizes CDK2 transcriptCDK2ADAR1 stabilizes CDK2 a key player in cancer cell-cycle progression, so promoting GBM proliferation in vitro and most importantly in vivoHumans/cell lines/mice
ADAR3Coding geneQ/R, ADAR3 inhibits editing of the Q/R site by binding to the GRIA2 pre-mRNAGRIA2ADAR3 expression contributes to the relative level of GRIA2 editing in tumors from patients suffering from glioblastomaHumans/cell lines
ADAR3NAADAR3 leads to increased phosphorylation and translocation of NF-κB into the nucleusNF-κBADAR3 promotes NF-κB activation and a gene expression program that provides a growth advantage to glioblastoma cellsCell lines
Hepatocellular carcinomaADAR1Coding genep.M2269VFLNBHyper-editing of FLNB (filamin B, β) is closely linked to HCC pathogenesisHumans/cell lines/mice
ADAR1CircRNAA-to-I editing occurs near the location of reverse complementary matchesCircARSP91CircARSP91 downregulated by AR in an ADAR1-dependent manner, could inhibit HCC tumor growth both in vitro and in vivoHumans/cell lines/mice
ADAR1NANAITGA2ADAR1 enhances HCC metastasis by promoting tumor cells adhering to ECM via increasing ITGA2 expressionHumans/cell lines/mice
ADAR1MiRNAED_miR-3144-3p(3_A < G)miR-3144-3pADAR1 augments oncogenic MSI2 effects by editing miR-3144-3p and that the resultant ED_miR-3144-3p(3_A < G) simultaneously suppresses tumor suppressor SLC38A4 expression, contributing to hepatocellular carcinogenesisHumans/cell lines/mice
ADAR1Coding genep.S367G. This substitution is predicted to cause a conformational change, resulting in a translocation from the cytoplasm to the nucleusAZIN1Edited AZIN1 has a stronger affinity to antizyme and promotes cell proliferation through the neutralization of antizyme-mediated degradation of ODC and CCND1Humans/cell lines/mice
Lung cancerADAR1Coding gene and MiRNAp.K242R. ADAR1 binds and edits on the neighboring pri-miR-381 sequenceNEIL1 and miR-381ADAR1 promotes tumor growth and mediates the regulation of A-to-I editing in both coding (NEIL1) and noncoding (miR-381) RNA transcriptsHumans/cell lines/mice
ADAR1NANACX3CR1ADAR1 deficiency increases the sensitivity of NSCLC/AR cells to Anlotinib by downregulating CX3CL1Cell lines/mice
ADAR13′UTRADAR1 mainly binds to the segment chr17: 82034049-82034204 of the 3ʹ-UTR in RAC3 mRNADDX1DDX1 mediates chemosensitivity to cisplatin via the ADAR1/RAC3 axis and promotes cancer progressionHumans/cell lines/mice
ADAR1IntronTargets a specific region within an intron on chromosome 8 (position 141,702,274) in the FAK transcript, leading to enhanced stability of FAK mRNAFAKADAR1 increases FAK protein abundance posttranscriptionally by binding to the FAK transcript and modifying a specific intronic site, resulting in the increased stabilization of FAK mRNAHumans/cell lines
MelanomaADAR1MiRNAADAR1p150 increases and the expression level of miRNA-149*miRNA-149*ADAR1 forms a complex with Dicer and enhance the function of miRNA-149*, thereby promoting proliferation of melanoma cells and inhibited cell apoptosisHumans/cell lines
MesotheliomaADAR23′UTRADAR2 maintains the level of DHFRDHFR, FPGSADAR2 deficiency leads to upregulation of type 1 IFN response and sensitizes mesothelioma cells to pemetrexed via ADAR2/DHFR, FPGS pathwayHumans/cell lines
Multiple myelomaADAR1Coding genep.R701GGLI1Edited GL1 activates the Hedgehog pathway and promotes malignant self-renewal of multiple myeloma in vivo and immunomodulatory drug resistance in vitroHumans/cell lines/mice
ADAR1Coding gene (c.726A > G)p.K242RNEIL1Recoded NEIL1 protein demonstrated deficient oxidative damage repair capacity and loss-of-function characteristics.Humans/cell lines/mice
Pancreatic cancerADAR1Coding geneADAR1 suppresses the phosphorylation of AKT at
Ser-473 sites		AKT, c-MycADAR1 stabilizes c-Myc via AKT signaling, which contributes to cancer cell resistance to BET inhibitors in PC cellsHumans/cell lines/mice
ADAR1Coding geneA-to-I editing occurs in exon 12 of GLI1 mRNA, specifically at nucleotide position chr12:57864624GLI1, circNEIL3CircNEIL3 promotes the proliferation and metastasis of PC via the circNEIL3/miR-432-5p/ADAR1/GLI1/cell cycle and EMT axis and that its expression is negatively regulated by ADAR1 via a feedback loopHumans/cell lines/mice
Prostate cancerADAR1LncRNAADAR1 interacts with PRUNE2/PCA3 dsRNA and controls the levels of PRUNE2PCA3 and PRUNE2PCA3 as a transdominant negative oncogene that inhibits the unidentified tumor suppressor gene PRUNE2 at the RNA level through an ADAR-mediated mechanismHumans/cell lines/mice
Thyroid cancerADAR1MiRNAThe editing hotspot in miR-200b is located in its
seed region		miR-200bThe impaired ability of edited miR-200b to inhibit ZEB1 could promote motility and invasion in TC cellsHumans/cell lines/mice
ADAR1Coding gene (c.308A > G)p.Q103RCDK13Edited CDK13-Q103R stimulates a stronger cell proliferation and migration phenotype than WT CDK1Humans/cell lines
A-to-I suppressing cancer
Acute myeloid leukemiaADAR2Coding geneCOPA(p.I164V) COG3(p.I635V)COPA and COG3ADAR2 suppresses leukemogenesis specifically in t(8;21) and inv16 AML cells by the RUNX1-ETO AE9a fusion protein, targeting COPA and COG3 to inhibit clonogenic growth of human t(8;21) AML cellsHumans/cell lines/mice
Breast cancerADAR1Coding genep.I342MGABRA3Edited Gabra3 suppresses BC cell invasion and metastasisCell lines/mice
Colorectal cancerADAR2MiRNAADAR2 regulates the secretion of miR-200s or influences the levels of RBPs or other components of the miRNA secretion machinerymiR-200sPKCζ-phosphorylated ADAR2 promotes the accumulation of miR-200s and loss of the PKCζ/ADAR2 axis results in EMT and increased liver metastasesHumans/cell lines/mice
Esophageal squamous cell carcinomaADAR2Coding gene (c.284A > G)p.K95RIGFBP7ADAR2 edits and stabilizes IGFBP7 to suppresses tumor growth and induces apoptosis in ESCCHumans/cell lines/mice
Gastric cancerADAR2Coding genep.H241RPODXLEdited PODXL at codon 241 (His to Arg) confers a loss-of-function phenotype that neutralizes the tumorigenic ability of the unedited PODXLHumans/cell lines/mice
GlioblastomaADAR2MiRNAADAR2 reduces the levels of miR-221, -222 and -21 by preventing their precursors from maturing.miR-222/221 and miR-21ADAR2 edits miR-222/221 and miR-21 precursors and decreases the expression of the corresponding mature onco-miRNAs in vivo and in vitro, with significant effects on cell proliferation and migrationHumans/cell lines/mice
ADAR2IntronEdited CDC14B pre-mRNA enhances its expression and therefore reduces the skp2 target proteinCDC14BADAR2 inhibits astrocytoma growth by increasing the level of CDC14B, which in turn affects the Skp2/p21-p27 pathwayHumans/cell lines/mice
GliomaADAR2MiRNAThe A-to-I editing of miR-378a occurs within the seed regionmiR-376a*Unedited miR-376a* decreases RAP2A, but a modified miR-376a* causes an accumulation of AMFR, collectively leading to increased migration and invasiveness of glioma cellsHumans/cell lines/mice
ADAR3Coding genep.Q607RGRIA2Low expression of ADAR3 may induce unedited GRIA2 transcripts level that can promote cell migration and tumor invasionHumans/cell lines
Hepatocellular carcinomaADAR2SNPThe rs2253763 C-to-T change in ADAR2 3′UTR reduces
its interaction with miR-542-3p and allele-specifically elevates ADAR2 levels		rs2253763 genetic variantsThe rs2253763 SNP in ADAR2 3’-UTR could disturb miR-
542-3p binding, leading to dysregulated production of ADAR2 in an allelic way and ADAR2 could enhance oxaliplatin sensitivity		Humans/cell lines
ADAR2Coding genep.I164VCOPAHypo-editing of COPA (coatomer protein complex, subunit α) is closely linked to HCC pathogenesisHumans/cell lines/mice
MelanomaADAR1MiRNAADAR1 regulates biogenesis of miRNAs directly by potentially affecting Drosha complex and indirectly by regulating Dicer via let-7miR-17,
miR-432		Overexpression of miR-17-5p and miR-432 mediates the loss of ADAR1 in cancer cells and subsequently increases the malignant featuresHumans/cell lines/mice
ADAR1MiRNAThe reduction of ADAR1 results in aberrant miRNA processing, as well as alterations in the overall levels of mature miR-455-5pmiR-455-5pEdited miR-455-5p inhibits melanoma metastasis through promotion of the tumour suppressor gene CPEB1Cell lines/mice
ADAR1MiRNAEdited miR-22 regulates
the stability of the mRNA of ITGB3		ITGB3, miR-22 and PAX6ADAR1 regulates ITGB3 expression via miR-22 and PAX6 transcription factor both at the posttranscriptional and transcriptional levels, respectivelyHumans/cell lines
ADAR1MiRNAReduced miR-30a/d lead to a significant increase in ITGB3
expression in all three melanoma lines at the mRNA level		ITGB3, miR-30a and miR-30dADAR1 regulates ITGB3 by pointing on miR-30a and miR-30d as ADAR1-controlled microRNAs, which play a direct role in the posttranscriptional expression control of ITGB3 and of the invasive melanoma cell phenotypeHumans/cell lines/mice
ADAR1MiRNAADAR1 influences the transcription of miR222 precursorsmiR-222ADAR1 regulates the biogenesis of miR222 and thereby ICAM1 expression, which consequently affects melanoma immune resistanceHumans/cell lines
ADAR1MiRNAThe A-to-I editing of miR-378a-3p is non-canonical and it occurs outside the seed regionmiR-378a-3pEdited miR-378a-3p binds to the 3ʹ-UTR of the PARVA oncogene and inhibits its expression, thus preventing the progression of melanoma towards the malignant phenotypeCell lines/mice
Thyroid cancerADAR3SNPThe ADAR3 rs904957 polymorphism, which involves a thymine-to-cytosine (T-to-C) change in the 3′UTR, increases the binding affinity of miR-1180-3p and suppresses ADAR3rs904957 genetic variantsADAR3 rs904957 genetic polymorphism located in the gene 3’-UTR results in allelic downregulation of ADAR3 expression and miR-1180-3p posttranscriptionally suppresses ADARB2 expressionHumans/cell lines
Cancer typesA-to-I modifierA-to-I editing siteImpact on mRNA/proteinGene(s) involvedFunctional implicationsOrganisms
A-to-I promoting cancer
Acute lymphoblastic leukemiaADAR1SNPThe variations are expected to disrupt or enhance interaction with other transcriptional regulatory proteinsrs9616 and rs2229857 genetic variantsThe variant at rs9616 and rs2229857 modulates ADAR1 expression and confers a predisposition and relapse risk to ALLHumans/cell lines
Breast cancerADAR1MiRNA, 3ʹUTRRNA editing stabilizes DHFR mRNAmiR-25-3p and miR-125a-3p, DHFRDHFR is posttranscriptionally regulated through ADAR1-mediated RNA editing by editing the miR-25-3p and miR-125a-3p binding sites in the 3’-UTR of DHFR, affecting cell proliferation and sensitivity of BC cells to methotrexateHumans/cell lines
ADAR1MiRNA, 3ʹUTRIncreases METTL3 mRNA and protein levelsMETTL3ADAR1 edits METTL3 mRNA and changes its binding site to miR532-5p, leading to increased METTL3 protein, which further targets ARHGAP5, recognized by YTHDF1 to promote the proliferation, migration, and invasion of BC cellsHumans/cell lines/mice
ADAR1LncRNAAlters LINC00944 expression levels by means of noncanonical functionsLINC00944Edited lncRNA LINC00944 is immune-related and positively correlates to tumor infiltrating T lymphocytes, the age at diagnosis, tumor size, and poor prognosisHumans/cell lines
ADAR1LncRNALINC00624
promotes ADAR1 RNA editing ability by regulating
ADAR1 expression		LINC00624Edited LINC00624 inhibits MHC class I antigen presentation and limits CD8 + Tcell infiltration in the BC microenvironmentHumans/cell lines/mice
ADAR1NANAKYNUEdited KYNU is associated with aggressiveness of BCHumans/cell lines
ADAR1Coding genep.M2293V. The editing reduces FLNB activity via disruption of binding partners
and consequently of localization		FLNB, miR-27a-5p and miR-4485-3pEdited FLNB reduces the tumor suppressive activities of the protein, thereby promoting growth and invasion in TNBC. ADAR1-downregulated miRNAs 27a-5p and miR-4485-3p inhibit cell-cycle progression, and that miR-27a-5p also suppresses invasion and promotes IL6/TNF expression in TNBC cellsCell lines
Cervical cancerADAR1Coding geneY/C, Q/RBLCAPEdited BLCAP regulates the STAT3 signaling pathway to promote the progression of CC carcinogenesisHumans/cell lines
Chronic myeloid leukemiaADAR1IntronADAR1 drives alternative splicing of GSK3βGSK3βADAR1 induces mis-splicing of GSK3β resulting in the renewal of leukemia stem cellHumans/cell lines/mice
ADAR1MiRNAA-to-G nucleotide changes at + 3 and + 59 editing sites may alter RNA secondary structures at DROSHA/DGCR8 and DICER cleavage sitesLet-7ADAR1 reduces let-7 levels and enhances leukemic stem cell renewalHumans/cell lines/mice
ADAR1MiRNAADAR1 hinders pri-miR-26a biogenesis by preventing
DROSHA cleavage		miR-26aADAR1 reduces the maturation of miR-26a, which indirectly represses CDKN1A expression via EZH2, hence regulating cell-cycle transitHumans/cell lines/mice
ADAR13ʹUTRADAR1 reduces miR-155 expressionMDM2ADAR1 edits the 3ʹUTR of MDM2 to prevent targeting by miR-155, leading to increase MDM2 levels and inhibit the activation of p53, thereby promoting the progression of CMLHumans/cell lines/mice
Colorectal cancerADAR1Coding geneS/GAZIN1Edited AZIN1 enhances stemness and appears to drive the metastatic processHumans/cell lines/mice
ADAR2Coding geneQ/R in the fifth amino acid of the BLCAP proteinBLCAPEdited BLCAP facilitates the transition from G1 to S phase of the cell cycle through the loss of repressive effect on Rb1, leading to the increased cell proliferation and reduced apoptosisHumans/cell lines/mice
ADAR13ʹ-UTRIncreases the RNA stabilityPVRADAR-mediated RNA editing may enhance tumor- and immune-related gene activities and pathways in CRC by upregulating PVR expression.Human/cell lines
ADAR1Coding geneS/GAZIN1Edited AZIN1 enhances the invasive potential of CAFs within the TMEHumans/cell lines
Esophageal squamous cell carcinomaADAR1Coding genep.S367GAZIN1Edited AZIN1 transcript is more abundant in tumors, resulting in “gain of function” phenotypes during ESCC progressionHumans/cell lines/mice
ADAR1NANASOX2Oncogenic Sox2 activates endogenous retroviruses, inducing expression of dsRNA and dependence on the ADAR1Human/cell lines/mice
ADAR2Coding gene (c.261A > G)p.N72DSLC22A3Deregulation of SLC22A3 facilitates cell invasion and filopodia formation by reducing its direct association with ACTN4, leading to the increased actin-binding activity of ACTN4 in normal esophageal cellsHumans/cell lines/mice
Gastric cancerADAR1NANAmTORADAR1 activates mTOR/p70S6K/S6 ribosomal protein signaling axis to regulate protein translation, cell proliferation, and autophagyHumans/cell lines/mice
ADAR1MiRNAADAR1 mediates its effect via the interaction with DROSHA or by regulating the transcription of miR-302/367 clustermiR-302a-3p and IRF9ADAR1 regulates IFN signaling through the suppression of STAT1 and IRF9 via miR-302aCell lines
ADAR13′UTRA-to-I editing on 3′UTR of
SCD1 enhances binding of KHDRBS1, thereby increasing SCD1 mRNA stability		SCD1ADAR1/SCD1 axis governs chemoresistance by enhancing lipid droplet formation to neutralize ER stress induced by chemotherapyHumans/cell lines/mice
ADAR1CircRNAADAR1 has the ability to reduce the abundance of hsa_circ_0004872 in GC cellshsa_circ_0004872 and miR-224ADAR1 inhibits the expression of hsa_circ_0004872, which led to the upregulation of miR-224. Smad4, the target of miR-224, could further influence hsa_circ_0004872 levels by binding directly to the promoter region of ADAR1 to inhibit ADAR1 expressionHumans/cell lines/mice
GlioblastomaADAR1NAADAR1 binds and stabilizes CDK2 transcriptCDK2ADAR1 stabilizes CDK2 a key player in cancer cell-cycle progression, so promoting GBM proliferation in vitro and most importantly in vivoHumans/cell lines/mice
ADAR3Coding geneQ/R, ADAR3 inhibits editing of the Q/R site by binding to the GRIA2 pre-mRNAGRIA2ADAR3 expression contributes to the relative level of GRIA2 editing in tumors from patients suffering from glioblastomaHumans/cell lines
ADAR3NAADAR3 leads to increased phosphorylation and translocation of NF-κB into the nucleusNF-κBADAR3 promotes NF-κB activation and a gene expression program that provides a growth advantage to glioblastoma cellsCell lines
Hepatocellular carcinomaADAR1Coding genep.M2269VFLNBHyper-editing of FLNB (filamin B, β) is closely linked to HCC pathogenesisHumans/cell lines/mice
ADAR1CircRNAA-to-I editing occurs near the location of reverse complementary matchesCircARSP91CircARSP91 downregulated by AR in an ADAR1-dependent manner, could inhibit HCC tumor growth both in vitro and in vivoHumans/cell lines/mice
ADAR1NANAITGA2ADAR1 enhances HCC metastasis by promoting tumor cells adhering to ECM via increasing ITGA2 expressionHumans/cell lines/mice
ADAR1MiRNAED_miR-3144-3p(3_A < G)miR-3144-3pADAR1 augments oncogenic MSI2 effects by editing miR-3144-3p and that the resultant ED_miR-3144-3p(3_A < G) simultaneously suppresses tumor suppressor SLC38A4 expression, contributing to hepatocellular carcinogenesisHumans/cell lines/mice
ADAR1Coding genep.S367G. This substitution is predicted to cause a conformational change, resulting in a translocation from the cytoplasm to the nucleusAZIN1Edited AZIN1 has a stronger affinity to antizyme and promotes cell proliferation through the neutralization of antizyme-mediated degradation of ODC and CCND1Humans/cell lines/mice
Lung cancerADAR1Coding gene and MiRNAp.K242R. ADAR1 binds and edits on the neighboring pri-miR-381 sequenceNEIL1 and miR-381ADAR1 promotes tumor growth and mediates the regulation of A-to-I editing in both coding (NEIL1) and noncoding (miR-381) RNA transcriptsHumans/cell lines/mice
ADAR1NANACX3CR1ADAR1 deficiency increases the sensitivity of NSCLC/AR cells to Anlotinib by downregulating CX3CL1Cell lines/mice
ADAR13′UTRADAR1 mainly binds to the segment chr17: 82034049-82034204 of the 3ʹ-UTR in RAC3 mRNADDX1DDX1 mediates chemosensitivity to cisplatin via the ADAR1/RAC3 axis and promotes cancer progressionHumans/cell lines/mice
ADAR1IntronTargets a specific region within an intron on chromosome 8 (position 141,702,274) in the FAK transcript, leading to enhanced stability of FAK mRNAFAKADAR1 increases FAK protein abundance posttranscriptionally by binding to the FAK transcript and modifying a specific intronic site, resulting in the increased stabilization of FAK mRNAHumans/cell lines
MelanomaADAR1MiRNAADAR1p150 increases and the expression level of miRNA-149*miRNA-149*ADAR1 forms a complex with Dicer and enhance the function of miRNA-149*, thereby promoting proliferation of melanoma cells and inhibited cell apoptosisHumans/cell lines
MesotheliomaADAR23′UTRADAR2 maintains the level of DHFRDHFR, FPGSADAR2 deficiency leads to upregulation of type 1 IFN response and sensitizes mesothelioma cells to pemetrexed via ADAR2/DHFR, FPGS pathwayHumans/cell lines
Multiple myelomaADAR1Coding genep.R701GGLI1Edited GL1 activates the Hedgehog pathway and promotes malignant self-renewal of multiple myeloma in vivo and immunomodulatory drug resistance in vitroHumans/cell lines/mice
ADAR1Coding gene (c.726A > G)p.K242RNEIL1Recoded NEIL1 protein demonstrated deficient oxidative damage repair capacity and loss-of-function characteristics.Humans/cell lines/mice
Pancreatic cancerADAR1Coding geneADAR1 suppresses the phosphorylation of AKT at
Ser-473 sites		AKT, c-MycADAR1 stabilizes c-Myc via AKT signaling, which contributes to cancer cell resistance to BET inhibitors in PC cellsHumans/cell lines/mice
ADAR1Coding geneA-to-I editing occurs in exon 12 of GLI1 mRNA, specifically at nucleotide position chr12:57864624GLI1, circNEIL3CircNEIL3 promotes the proliferation and metastasis of PC via the circNEIL3/miR-432-5p/ADAR1/GLI1/cell cycle and EMT axis and that its expression is negatively regulated by ADAR1 via a feedback loopHumans/cell lines/mice
Prostate cancerADAR1LncRNAADAR1 interacts with PRUNE2/PCA3 dsRNA and controls the levels of PRUNE2PCA3 and PRUNE2PCA3 as a transdominant negative oncogene that inhibits the unidentified tumor suppressor gene PRUNE2 at the RNA level through an ADAR-mediated mechanismHumans/cell lines/mice
Thyroid cancerADAR1MiRNAThe editing hotspot in miR-200b is located in its
seed region		miR-200bThe impaired ability of edited miR-200b to inhibit ZEB1 could promote motility and invasion in TC cellsHumans/cell lines/mice
ADAR1Coding gene (c.308A > G)p.Q103RCDK13Edited CDK13-Q103R stimulates a stronger cell proliferation and migration phenotype than WT CDK1Humans/cell lines
A-to-I suppressing cancer
Acute myeloid leukemiaADAR2Coding geneCOPA(p.I164V) COG3(p.I635V)COPA and COG3ADAR2 suppresses leukemogenesis specifically in t(8;21) and inv16 AML cells by the RUNX1-ETO AE9a fusion protein, targeting COPA and COG3 to inhibit clonogenic growth of human t(8;21) AML cellsHumans/cell lines/mice
Breast cancerADAR1Coding genep.I342MGABRA3Edited Gabra3 suppresses BC cell invasion and metastasisCell lines/mice
Colorectal cancerADAR2MiRNAADAR2 regulates the secretion of miR-200s or influences the levels of RBPs or other components of the miRNA secretion machinerymiR-200sPKCζ-phosphorylated ADAR2 promotes the accumulation of miR-200s and loss of the PKCζ/ADAR2 axis results in EMT and increased liver metastasesHumans/cell lines/mice
Esophageal squamous cell carcinomaADAR2Coding gene (c.284A > G)p.K95RIGFBP7ADAR2 edits and stabilizes IGFBP7 to suppresses tumor growth and induces apoptosis in ESCCHumans/cell lines/mice
Gastric cancerADAR2Coding genep.H241RPODXLEdited PODXL at codon 241 (His to Arg) confers a loss-of-function phenotype that neutralizes the tumorigenic ability of the unedited PODXLHumans/cell lines/mice
GlioblastomaADAR2MiRNAADAR2 reduces the levels of miR-221, -222 and -21 by preventing their precursors from maturing.miR-222/221 and miR-21ADAR2 edits miR-222/221 and miR-21 precursors and decreases the expression of the corresponding mature onco-miRNAs in vivo and in vitro, with significant effects on cell proliferation and migrationHumans/cell lines/mice
ADAR2IntronEdited CDC14B pre-mRNA enhances its expression and therefore reduces the skp2 target proteinCDC14BADAR2 inhibits astrocytoma growth by increasing the level of CDC14B, which in turn affects the Skp2/p21-p27 pathwayHumans/cell lines/mice
GliomaADAR2MiRNAThe A-to-I editing of miR-378a occurs within the seed regionmiR-376a*Unedited miR-376a* decreases RAP2A, but a modified miR-376a* causes an accumulation of AMFR, collectively leading to increased migration and invasiveness of glioma cellsHumans/cell lines/mice
ADAR3Coding genep.Q607RGRIA2Low expression of ADAR3 may induce unedited GRIA2 transcripts level that can promote cell migration and tumor invasionHumans/cell lines
Hepatocellular carcinomaADAR2SNPThe rs2253763 C-to-T change in ADAR2 3′UTR reduces
its interaction with miR-542-3p and allele-specifically elevates ADAR2 levels		rs2253763 genetic variantsThe rs2253763 SNP in ADAR2 3’-UTR could disturb miR-
542-3p binding, leading to dysregulated production of ADAR2 in an allelic way and ADAR2 could enhance oxaliplatin sensitivity		Humans/cell lines
ADAR2Coding genep.I164VCOPAHypo-editing of COPA (coatomer protein complex, subunit α) is closely linked to HCC pathogenesisHumans/cell lines/mice
MelanomaADAR1MiRNAADAR1 regulates biogenesis of miRNAs directly by potentially affecting Drosha complex and indirectly by regulating Dicer via let-7miR-17,
miR-432		Overexpression of miR-17-5p and miR-432 mediates the loss of ADAR1 in cancer cells and subsequently increases the malignant featuresHumans/cell lines/mice
ADAR1MiRNAThe reduction of ADAR1 results in aberrant miRNA processing, as well as alterations in the overall levels of mature miR-455-5pmiR-455-5pEdited miR-455-5p inhibits melanoma metastasis through promotion of the tumour suppressor gene CPEB1Cell lines/mice
ADAR1MiRNAEdited miR-22 regulates
the stability of the mRNA of ITGB3		ITGB3, miR-22 and PAX6ADAR1 regulates ITGB3 expression via miR-22 and PAX6 transcription factor both at the posttranscriptional and transcriptional levels, respectivelyHumans/cell lines
ADAR1MiRNAReduced miR-30a/d lead to a significant increase in ITGB3
expression in all three melanoma lines at the mRNA level		ITGB3, miR-30a and miR-30dADAR1 regulates ITGB3 by pointing on miR-30a and miR-30d as ADAR1-controlled microRNAs, which play a direct role in the posttranscriptional expression control of ITGB3 and of the invasive melanoma cell phenotypeHumans/cell lines/mice
ADAR1MiRNAADAR1 influences the transcription of miR222 precursorsmiR-222ADAR1 regulates the biogenesis of miR222 and thereby ICAM1 expression, which consequently affects melanoma immune resistanceHumans/cell lines
ADAR1MiRNAThe A-to-I editing of miR-378a-3p is non-canonical and it occurs outside the seed regionmiR-378a-3pEdited miR-378a-3p binds to the 3ʹ-UTR of the PARVA oncogene and inhibits its expression, thus preventing the progression of melanoma towards the malignant phenotypeCell lines/mice
Thyroid cancerADAR3SNPThe ADAR3 rs904957 polymorphism, which involves a thymine-to-cytosine (T-to-C) change in the 3′UTR, increases the binding affinity of miR-1180-3p and suppresses ADAR3rs904957 genetic variantsADAR3 rs904957 genetic polymorphism located in the gene 3’-UTR results in allelic downregulation of ADAR3 expression and miR-1180-3p posttranscriptionally suppresses ADARB2 expressionHumans/cell lines

NA: not available.

Table 1.
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Summary of the function and downstream targets of A-to-I modification in cancer.

Cancer typesA-to-I modifierA-to-I editing siteImpact on mRNA/proteinGene(s) involvedFunctional implicationsOrganisms
A-to-I promoting cancer
Acute lymphoblastic leukemiaADAR1SNPThe variations are expected to disrupt or enhance interaction with other transcriptional regulatory proteinsrs9616 and rs2229857 genetic variantsThe variant at rs9616 and rs2229857 modulates ADAR1 expression and confers a predisposition and relapse risk to ALLHumans/cell lines
Breast cancerADAR1MiRNA, 3ʹUTRRNA editing stabilizes DHFR mRNAmiR-25-3p and miR-125a-3p, DHFRDHFR is posttranscriptionally regulated through ADAR1-mediated RNA editing by editing the miR-25-3p and miR-125a-3p binding sites in the 3’-UTR of DHFR, affecting cell proliferation and sensitivity of BC cells to methotrexateHumans/cell lines
ADAR1MiRNA, 3ʹUTRIncreases METTL3 mRNA and protein levelsMETTL3ADAR1 edits METTL3 mRNA and changes its binding site to miR532-5p, leading to increased METTL3 protein, which further targets ARHGAP5, recognized by YTHDF1 to promote the proliferation, migration, and invasion of BC cellsHumans/cell lines/mice
ADAR1LncRNAAlters LINC00944 expression levels by means of noncanonical functionsLINC00944Edited lncRNA LINC00944 is immune-related and positively correlates to tumor infiltrating T lymphocytes, the age at diagnosis, tumor size, and poor prognosisHumans/cell lines
ADAR1LncRNALINC00624
promotes ADAR1 RNA editing ability by regulating
ADAR1 expression		LINC00624Edited LINC00624 inhibits MHC class I antigen presentation and limits CD8 + Tcell infiltration in the BC microenvironmentHumans/cell lines/mice
ADAR1NANAKYNUEdited KYNU is associated with aggressiveness of BCHumans/cell lines
ADAR1Coding genep.M2293V. The editing reduces FLNB activity via disruption of binding partners
and consequently of localization		FLNB, miR-27a-5p and miR-4485-3pEdited FLNB reduces the tumor suppressive activities of the protein, thereby promoting growth and invasion in TNBC. ADAR1-downregulated miRNAs 27a-5p and miR-4485-3p inhibit cell-cycle progression, and that miR-27a-5p also suppresses invasion and promotes IL6/TNF expression in TNBC cellsCell lines
Cervical cancerADAR1Coding geneY/C, Q/RBLCAPEdited BLCAP regulates the STAT3 signaling pathway to promote the progression of CC carcinogenesisHumans/cell lines
Chronic myeloid leukemiaADAR1IntronADAR1 drives alternative splicing of GSK3βGSK3βADAR1 induces mis-splicing of GSK3β resulting in the renewal of leukemia stem cellHumans/cell lines/mice
ADAR1MiRNAA-to-G nucleotide changes at + 3 and + 59 editing sites may alter RNA secondary structures at DROSHA/DGCR8 and DICER cleavage sitesLet-7ADAR1 reduces let-7 levels and enhances leukemic stem cell renewalHumans/cell lines/mice
ADAR1MiRNAADAR1 hinders pri-miR-26a biogenesis by preventing
DROSHA cleavage		miR-26aADAR1 reduces the maturation of miR-26a, which indirectly represses CDKN1A expression via EZH2, hence regulating cell-cycle transitHumans/cell lines/mice
ADAR13ʹUTRADAR1 reduces miR-155 expressionMDM2ADAR1 edits the 3ʹUTR of MDM2 to prevent targeting by miR-155, leading to increase MDM2 levels and inhibit the activation of p53, thereby promoting the progression of CMLHumans/cell lines/mice
Colorectal cancerADAR1Coding geneS/GAZIN1Edited AZIN1 enhances stemness and appears to drive the metastatic processHumans/cell lines/mice
ADAR2Coding geneQ/R in the fifth amino acid of the BLCAP proteinBLCAPEdited BLCAP facilitates the transition from G1 to S phase of the cell cycle through the loss of repressive effect on Rb1, leading to the increased cell proliferation and reduced apoptosisHumans/cell lines/mice
ADAR13ʹ-UTRIncreases the RNA stabilityPVRADAR-mediated RNA editing may enhance tumor- and immune-related gene activities and pathways in CRC by upregulating PVR expression.Human/cell lines
ADAR1Coding geneS/GAZIN1Edited AZIN1 enhances the invasive potential of CAFs within the TMEHumans/cell lines
Esophageal squamous cell carcinomaADAR1Coding genep.S367GAZIN1Edited AZIN1 transcript is more abundant in tumors, resulting in “gain of function” phenotypes during ESCC progressionHumans/cell lines/mice
ADAR1NANASOX2Oncogenic Sox2 activates endogenous retroviruses, inducing expression of dsRNA and dependence on the ADAR1Human/cell lines/mice
ADAR2Coding gene (c.261A > G)p.N72DSLC22A3Deregulation of SLC22A3 facilitates cell invasion and filopodia formation by reducing its direct association with ACTN4, leading to the increased actin-binding activity of ACTN4 in normal esophageal cellsHumans/cell lines/mice
Gastric cancerADAR1NANAmTORADAR1 activates mTOR/p70S6K/S6 ribosomal protein signaling axis to regulate protein translation, cell proliferation, and autophagyHumans/cell lines/mice
ADAR1MiRNAADAR1 mediates its effect via the interaction with DROSHA or by regulating the transcription of miR-302/367 clustermiR-302a-3p and IRF9ADAR1 regulates IFN signaling through the suppression of STAT1 and IRF9 via miR-302aCell lines
ADAR13′UTRA-to-I editing on 3′UTR of
SCD1 enhances binding of KHDRBS1, thereby increasing SCD1 mRNA stability		SCD1ADAR1/SCD1 axis governs chemoresistance by enhancing lipid droplet formation to neutralize ER stress induced by chemotherapyHumans/cell lines/mice
ADAR1CircRNAADAR1 has the ability to reduce the abundance of hsa_circ_0004872 in GC cellshsa_circ_0004872 and miR-224ADAR1 inhibits the expression of hsa_circ_0004872, which led to the upregulation of miR-224. Smad4, the target of miR-224, could further influence hsa_circ_0004872 levels by binding directly to the promoter region of ADAR1 to inhibit ADAR1 expressionHumans/cell lines/mice
GlioblastomaADAR1NAADAR1 binds and stabilizes CDK2 transcriptCDK2ADAR1 stabilizes CDK2 a key player in cancer cell-cycle progression, so promoting GBM proliferation in vitro and most importantly in vivoHumans/cell lines/mice
ADAR3Coding geneQ/R, ADAR3 inhibits editing of the Q/R site by binding to the GRIA2 pre-mRNAGRIA2ADAR3 expression contributes to the relative level of GRIA2 editing in tumors from patients suffering from glioblastomaHumans/cell lines
ADAR3NAADAR3 leads to increased phosphorylation and translocation of NF-κB into the nucleusNF-κBADAR3 promotes NF-κB activation and a gene expression program that provides a growth advantage to glioblastoma cellsCell lines
Hepatocellular carcinomaADAR1Coding genep.M2269VFLNBHyper-editing of FLNB (filamin B, β) is closely linked to HCC pathogenesisHumans/cell lines/mice
ADAR1CircRNAA-to-I editing occurs near the location of reverse complementary matchesCircARSP91CircARSP91 downregulated by AR in an ADAR1-dependent manner, could inhibit HCC tumor growth both in vitro and in vivoHumans/cell lines/mice
ADAR1NANAITGA2ADAR1 enhances HCC metastasis by promoting tumor cells adhering to ECM via increasing ITGA2 expressionHumans/cell lines/mice
ADAR1MiRNAED_miR-3144-3p(3_A < G)miR-3144-3pADAR1 augments oncogenic MSI2 effects by editing miR-3144-3p and that the resultant ED_miR-3144-3p(3_A < G) simultaneously suppresses tumor suppressor SLC38A4 expression, contributing to hepatocellular carcinogenesisHumans/cell lines/mice
ADAR1Coding genep.S367G. This substitution is predicted to cause a conformational change, resulting in a translocation from the cytoplasm to the nucleusAZIN1Edited AZIN1 has a stronger affinity to antizyme and promotes cell proliferation through the neutralization of antizyme-mediated degradation of ODC and CCND1Humans/cell lines/mice
Lung cancerADAR1Coding gene and MiRNAp.K242R. ADAR1 binds and edits on the neighboring pri-miR-381 sequenceNEIL1 and miR-381ADAR1 promotes tumor growth and mediates the regulation of A-to-I editing in both coding (NEIL1) and noncoding (miR-381) RNA transcriptsHumans/cell lines/mice
ADAR1NANACX3CR1ADAR1 deficiency increases the sensitivity of NSCLC/AR cells to Anlotinib by downregulating CX3CL1Cell lines/mice
ADAR13′UTRADAR1 mainly binds to the segment chr17: 82034049-82034204 of the 3ʹ-UTR in RAC3 mRNADDX1DDX1 mediates chemosensitivity to cisplatin via the ADAR1/RAC3 axis and promotes cancer progressionHumans/cell lines/mice
ADAR1IntronTargets a specific region within an intron on chromosome 8 (position 141,702,274) in the FAK transcript, leading to enhanced stability of FAK mRNAFAKADAR1 increases FAK protein abundance posttranscriptionally by binding to the FAK transcript and modifying a specific intronic site, resulting in the increased stabilization of FAK mRNAHumans/cell lines
MelanomaADAR1MiRNAADAR1p150 increases and the expression level of miRNA-149*miRNA-149*ADAR1 forms a complex with Dicer and enhance the function of miRNA-149*, thereby promoting proliferation of melanoma cells and inhibited cell apoptosisHumans/cell lines
MesotheliomaADAR23′UTRADAR2 maintains the level of DHFRDHFR, FPGSADAR2 deficiency leads to upregulation of type 1 IFN response and sensitizes mesothelioma cells to pemetrexed via ADAR2/DHFR, FPGS pathwayHumans/cell lines
Multiple myelomaADAR1Coding genep.R701GGLI1Edited GL1 activates the Hedgehog pathway and promotes malignant self-renewal of multiple myeloma in vivo and immunomodulatory drug resistance in vitroHumans/cell lines/mice
ADAR1Coding gene (c.726A > G)p.K242RNEIL1Recoded NEIL1 protein demonstrated deficient oxidative damage repair capacity and loss-of-function characteristics.Humans/cell lines/mice
Pancreatic cancerADAR1Coding geneADAR1 suppresses the phosphorylation of AKT at
Ser-473 sites		AKT, c-MycADAR1 stabilizes c-Myc via AKT signaling, which contributes to cancer cell resistance to BET inhibitors in PC cellsHumans/cell lines/mice
ADAR1Coding geneA-to-I editing occurs in exon 12 of GLI1 mRNA, specifically at nucleotide position chr12:57864624GLI1, circNEIL3CircNEIL3 promotes the proliferation and metastasis of PC via the circNEIL3/miR-432-5p/ADAR1/GLI1/cell cycle and EMT axis and that its expression is negatively regulated by ADAR1 via a feedback loopHumans/cell lines/mice
Prostate cancerADAR1LncRNAADAR1 interacts with PRUNE2/PCA3 dsRNA and controls the levels of PRUNE2PCA3 and PRUNE2PCA3 as a transdominant negative oncogene that inhibits the unidentified tumor suppressor gene PRUNE2 at the RNA level through an ADAR-mediated mechanismHumans/cell lines/mice
Thyroid cancerADAR1MiRNAThe editing hotspot in miR-200b is located in its
seed region		miR-200bThe impaired ability of edited miR-200b to inhibit ZEB1 could promote motility and invasion in TC cellsHumans/cell lines/mice
ADAR1Coding gene (c.308A > G)p.Q103RCDK13Edited CDK13-Q103R stimulates a stronger cell proliferation and migration phenotype than WT CDK1Humans/cell lines
A-to-I suppressing cancer
Acute myeloid leukemiaADAR2Coding geneCOPA(p.I164V) COG3(p.I635V)COPA and COG3ADAR2 suppresses leukemogenesis specifically in t(8;21) and inv16 AML cells by the RUNX1-ETO AE9a fusion protein, targeting COPA and COG3 to inhibit clonogenic growth of human t(8;21) AML cellsHumans/cell lines/mice
Breast cancerADAR1Coding genep.I342MGABRA3Edited Gabra3 suppresses BC cell invasion and metastasisCell lines/mice
Colorectal cancerADAR2MiRNAADAR2 regulates the secretion of miR-200s or influences the levels of RBPs or other components of the miRNA secretion machinerymiR-200sPKCζ-phosphorylated ADAR2 promotes the accumulation of miR-200s and loss of the PKCζ/ADAR2 axis results in EMT and increased liver metastasesHumans/cell lines/mice
Esophageal squamous cell carcinomaADAR2Coding gene (c.284A > G)p.K95RIGFBP7ADAR2 edits and stabilizes IGFBP7 to suppresses tumor growth and induces apoptosis in ESCCHumans/cell lines/mice
Gastric cancerADAR2Coding genep.H241RPODXLEdited PODXL at codon 241 (His to Arg) confers a loss-of-function phenotype that neutralizes the tumorigenic ability of the unedited PODXLHumans/cell lines/mice
GlioblastomaADAR2MiRNAADAR2 reduces the levels of miR-221, -222 and -21 by preventing their precursors from maturing.miR-222/221 and miR-21ADAR2 edits miR-222/221 and miR-21 precursors and decreases the expression of the corresponding mature onco-miRNAs in vivo and in vitro, with significant effects on cell proliferation and migrationHumans/cell lines/mice
ADAR2IntronEdited CDC14B pre-mRNA enhances its expression and therefore reduces the skp2 target proteinCDC14BADAR2 inhibits astrocytoma growth by increasing the level of CDC14B, which in turn affects the Skp2/p21-p27 pathwayHumans/cell lines/mice
GliomaADAR2MiRNAThe A-to-I editing of miR-378a occurs within the seed regionmiR-376a*Unedited miR-376a* decreases RAP2A, but a modified miR-376a* causes an accumulation of AMFR, collectively leading to increased migration and invasiveness of glioma cellsHumans/cell lines/mice
ADAR3Coding genep.Q607RGRIA2Low expression of ADAR3 may induce unedited GRIA2 transcripts level that can promote cell migration and tumor invasionHumans/cell lines
Hepatocellular carcinomaADAR2SNPThe rs2253763 C-to-T change in ADAR2 3′UTR reduces
its interaction with miR-542-3p and allele-specifically elevates ADAR2 levels		rs2253763 genetic variantsThe rs2253763 SNP in ADAR2 3’-UTR could disturb miR-
542-3p binding, leading to dysregulated production of ADAR2 in an allelic way and ADAR2 could enhance oxaliplatin sensitivity		Humans/cell lines
ADAR2Coding genep.I164VCOPAHypo-editing of COPA (coatomer protein complex, subunit α) is closely linked to HCC pathogenesisHumans/cell lines/mice
MelanomaADAR1MiRNAADAR1 regulates biogenesis of miRNAs directly by potentially affecting Drosha complex and indirectly by regulating Dicer via let-7miR-17,
miR-432		Overexpression of miR-17-5p and miR-432 mediates the loss of ADAR1 in cancer cells and subsequently increases the malignant featuresHumans/cell lines/mice
ADAR1MiRNAThe reduction of ADAR1 results in aberrant miRNA processing, as well as alterations in the overall levels of mature miR-455-5pmiR-455-5pEdited miR-455-5p inhibits melanoma metastasis through promotion of the tumour suppressor gene CPEB1Cell lines/mice
ADAR1MiRNAEdited miR-22 regulates
the stability of the mRNA of ITGB3		ITGB3, miR-22 and PAX6ADAR1 regulates ITGB3 expression via miR-22 and PAX6 transcription factor both at the posttranscriptional and transcriptional levels, respectivelyHumans/cell lines
ADAR1MiRNAReduced miR-30a/d lead to a significant increase in ITGB3
expression in all three melanoma lines at the mRNA level		ITGB3, miR-30a and miR-30dADAR1 regulates ITGB3 by pointing on miR-30a and miR-30d as ADAR1-controlled microRNAs, which play a direct role in the posttranscriptional expression control of ITGB3 and of the invasive melanoma cell phenotypeHumans/cell lines/mice
ADAR1MiRNAADAR1 influences the transcription of miR222 precursorsmiR-222ADAR1 regulates the biogenesis of miR222 and thereby ICAM1 expression, which consequently affects melanoma immune resistanceHumans/cell lines
ADAR1MiRNAThe A-to-I editing of miR-378a-3p is non-canonical and it occurs outside the seed regionmiR-378a-3pEdited miR-378a-3p binds to the 3ʹ-UTR of the PARVA oncogene and inhibits its expression, thus preventing the progression of melanoma towards the malignant phenotypeCell lines/mice
Thyroid cancerADAR3SNPThe ADAR3 rs904957 polymorphism, which involves a thymine-to-cytosine (T-to-C) change in the 3′UTR, increases the binding affinity of miR-1180-3p and suppresses ADAR3rs904957 genetic variantsADAR3 rs904957 genetic polymorphism located in the gene 3’-UTR results in allelic downregulation of ADAR3 expression and miR-1180-3p posttranscriptionally suppresses ADARB2 expressionHumans/cell lines
Cancer typesA-to-I modifierA-to-I editing siteImpact on mRNA/proteinGene(s) involvedFunctional implicationsOrganisms
A-to-I promoting cancer
Acute lymphoblastic leukemiaADAR1SNPThe variations are expected to disrupt or enhance interaction with other transcriptional regulatory proteinsrs9616 and rs2229857 genetic variantsThe variant at rs9616 and rs2229857 modulates ADAR1 expression and confers a predisposition and relapse risk to ALLHumans/cell lines
Breast cancerADAR1MiRNA, 3ʹUTRRNA editing stabilizes DHFR mRNAmiR-25-3p and miR-125a-3p, DHFRDHFR is posttranscriptionally regulated through ADAR1-mediated RNA editing by editing the miR-25-3p and miR-125a-3p binding sites in the 3’-UTR of DHFR, affecting cell proliferation and sensitivity of BC cells to methotrexateHumans/cell lines
ADAR1MiRNA, 3ʹUTRIncreases METTL3 mRNA and protein levelsMETTL3ADAR1 edits METTL3 mRNA and changes its binding site to miR532-5p, leading to increased METTL3 protein, which further targets ARHGAP5, recognized by YTHDF1 to promote the proliferation, migration, and invasion of BC cellsHumans/cell lines/mice
ADAR1LncRNAAlters LINC00944 expression levels by means of noncanonical functionsLINC00944Edited lncRNA LINC00944 is immune-related and positively correlates to tumor infiltrating T lymphocytes, the age at diagnosis, tumor size, and poor prognosisHumans/cell lines
ADAR1LncRNALINC00624
promotes ADAR1 RNA editing ability by regulating
ADAR1 expression		LINC00624Edited LINC00624 inhibits MHC class I antigen presentation and limits CD8 + Tcell infiltration in the BC microenvironmentHumans/cell lines/mice
ADAR1NANAKYNUEdited KYNU is associated with aggressiveness of BCHumans/cell lines
ADAR1Coding genep.M2293V. The editing reduces FLNB activity via disruption of binding partners
and consequently of localization		FLNB, miR-27a-5p and miR-4485-3pEdited FLNB reduces the tumor suppressive activities of the protein, thereby promoting growth and invasion in TNBC. ADAR1-downregulated miRNAs 27a-5p and miR-4485-3p inhibit cell-cycle progression, and that miR-27a-5p also suppresses invasion and promotes IL6/TNF expression in TNBC cellsCell lines
Cervical cancerADAR1Coding geneY/C, Q/RBLCAPEdited BLCAP regulates the STAT3 signaling pathway to promote the progression of CC carcinogenesisHumans/cell lines
Chronic myeloid leukemiaADAR1IntronADAR1 drives alternative splicing of GSK3βGSK3βADAR1 induces mis-splicing of GSK3β resulting in the renewal of leukemia stem cellHumans/cell lines/mice
ADAR1MiRNAA-to-G nucleotide changes at + 3 and + 59 editing sites may alter RNA secondary structures at DROSHA/DGCR8 and DICER cleavage sitesLet-7ADAR1 reduces let-7 levels and enhances leukemic stem cell renewalHumans/cell lines/mice
ADAR1MiRNAADAR1 hinders pri-miR-26a biogenesis by preventing
DROSHA cleavage		miR-26aADAR1 reduces the maturation of miR-26a, which indirectly represses CDKN1A expression via EZH2, hence regulating cell-cycle transitHumans/cell lines/mice
ADAR13ʹUTRADAR1 reduces miR-155 expressionMDM2ADAR1 edits the 3ʹUTR of MDM2 to prevent targeting by miR-155, leading to increase MDM2 levels and inhibit the activation of p53, thereby promoting the progression of CMLHumans/cell lines/mice
Colorectal cancerADAR1Coding geneS/GAZIN1Edited AZIN1 enhances stemness and appears to drive the metastatic processHumans/cell lines/mice
ADAR2Coding geneQ/R in the fifth amino acid of the BLCAP proteinBLCAPEdited BLCAP facilitates the transition from G1 to S phase of the cell cycle through the loss of repressive effect on Rb1, leading to the increased cell proliferation and reduced apoptosisHumans/cell lines/mice
ADAR13ʹ-UTRIncreases the RNA stabilityPVRADAR-mediated RNA editing may enhance tumor- and immune-related gene activities and pathways in CRC by upregulating PVR expression.Human/cell lines
ADAR1Coding geneS/GAZIN1Edited AZIN1 enhances the invasive potential of CAFs within the TMEHumans/cell lines
Esophageal squamous cell carcinomaADAR1Coding genep.S367GAZIN1Edited AZIN1 transcript is more abundant in tumors, resulting in “gain of function” phenotypes during ESCC progressionHumans/cell lines/mice
ADAR1NANASOX2Oncogenic Sox2 activates endogenous retroviruses, inducing expression of dsRNA and dependence on the ADAR1Human/cell lines/mice
ADAR2Coding gene (c.261A > G)p.N72DSLC22A3Deregulation of SLC22A3 facilitates cell invasion and filopodia formation by reducing its direct association with ACTN4, leading to the increased actin-binding activity of ACTN4 in normal esophageal cellsHumans/cell lines/mice
Gastric cancerADAR1NANAmTORADAR1 activates mTOR/p70S6K/S6 ribosomal protein signaling axis to regulate protein translation, cell proliferation, and autophagyHumans/cell lines/mice
ADAR1MiRNAADAR1 mediates its effect via the interaction with DROSHA or by regulating the transcription of miR-302/367 clustermiR-302a-3p and IRF9ADAR1 regulates IFN signaling through the suppression of STAT1 and IRF9 via miR-302aCell lines
ADAR13′UTRA-to-I editing on 3′UTR of
SCD1 enhances binding of KHDRBS1, thereby increasing SCD1 mRNA stability		SCD1ADAR1/SCD1 axis governs chemoresistance by enhancing lipid droplet formation to neutralize ER stress induced by chemotherapyHumans/cell lines/mice
ADAR1CircRNAADAR1 has the ability to reduce the abundance of hsa_circ_0004872 in GC cellshsa_circ_0004872 and miR-224ADAR1 inhibits the expression of hsa_circ_0004872, which led to the upregulation of miR-224. Smad4, the target of miR-224, could further influence hsa_circ_0004872 levels by binding directly to the promoter region of ADAR1 to inhibit ADAR1 expressionHumans/cell lines/mice
GlioblastomaADAR1NAADAR1 binds and stabilizes CDK2 transcriptCDK2ADAR1 stabilizes CDK2 a key player in cancer cell-cycle progression, so promoting GBM proliferation in vitro and most importantly in vivoHumans/cell lines/mice
ADAR3Coding geneQ/R, ADAR3 inhibits editing of the Q/R site by binding to the GRIA2 pre-mRNAGRIA2ADAR3 expression contributes to the relative level of GRIA2 editing in tumors from patients suffering from glioblastomaHumans/cell lines
ADAR3NAADAR3 leads to increased phosphorylation and translocation of NF-κB into the nucleusNF-κBADAR3 promotes NF-κB activation and a gene expression program that provides a growth advantage to glioblastoma cellsCell lines
Hepatocellular carcinomaADAR1Coding genep.M2269VFLNBHyper-editing of FLNB (filamin B, β) is closely linked to HCC pathogenesisHumans/cell lines/mice
ADAR1CircRNAA-to-I editing occurs near the location of reverse complementary matchesCircARSP91CircARSP91 downregulated by AR in an ADAR1-dependent manner, could inhibit HCC tumor growth both in vitro and in vivoHumans/cell lines/mice
ADAR1NANAITGA2ADAR1 enhances HCC metastasis by promoting tumor cells adhering to ECM via increasing ITGA2 expressionHumans/cell lines/mice
ADAR1MiRNAED_miR-3144-3p(3_A < G)miR-3144-3pADAR1 augments oncogenic MSI2 effects by editing miR-3144-3p and that the resultant ED_miR-3144-3p(3_A < G) simultaneously suppresses tumor suppressor SLC38A4 expression, contributing to hepatocellular carcinogenesisHumans/cell lines/mice
ADAR1Coding genep.S367G. This substitution is predicted to cause a conformational change, resulting in a translocation from the cytoplasm to the nucleusAZIN1Edited AZIN1 has a stronger affinity to antizyme and promotes cell proliferation through the neutralization of antizyme-mediated degradation of ODC and CCND1Humans/cell lines/mice
Lung cancerADAR1Coding gene and MiRNAp.K242R. ADAR1 binds and edits on the neighboring pri-miR-381 sequenceNEIL1 and miR-381ADAR1 promotes tumor growth and mediates the regulation of A-to-I editing in both coding (NEIL1) and noncoding (miR-381) RNA transcriptsHumans/cell lines/mice
ADAR1NANACX3CR1ADAR1 deficiency increases the sensitivity of NSCLC/AR cells to Anlotinib by downregulating CX3CL1Cell lines/mice
ADAR13′UTRADAR1 mainly binds to the segment chr17: 82034049-82034204 of the 3ʹ-UTR in RAC3 mRNADDX1DDX1 mediates chemosensitivity to cisplatin via the ADAR1/RAC3 axis and promotes cancer progressionHumans/cell lines/mice
ADAR1IntronTargets a specific region within an intron on chromosome 8 (position 141,702,274) in the FAK transcript, leading to enhanced stability of FAK mRNAFAKADAR1 increases FAK protein abundance posttranscriptionally by binding to the FAK transcript and modifying a specific intronic site, resulting in the increased stabilization of FAK mRNAHumans/cell lines
MelanomaADAR1MiRNAADAR1p150 increases and the expression level of miRNA-149*miRNA-149*ADAR1 forms a complex with Dicer and enhance the function of miRNA-149*, thereby promoting proliferation of melanoma cells and inhibited cell apoptosisHumans/cell lines
MesotheliomaADAR23′UTRADAR2 maintains the level of DHFRDHFR, FPGSADAR2 deficiency leads to upregulation of type 1 IFN response and sensitizes mesothelioma cells to pemetrexed via ADAR2/DHFR, FPGS pathwayHumans/cell lines
Multiple myelomaADAR1Coding genep.R701GGLI1Edited GL1 activates the Hedgehog pathway and promotes malignant self-renewal of multiple myeloma in vivo and immunomodulatory drug resistance in vitroHumans/cell lines/mice
ADAR1Coding gene (c.726A > G)p.K242RNEIL1Recoded NEIL1 protein demonstrated deficient oxidative damage repair capacity and loss-of-function characteristics.Humans/cell lines/mice
Pancreatic cancerADAR1Coding geneADAR1 suppresses the phosphorylation of AKT at
Ser-473 sites		AKT, c-MycADAR1 stabilizes c-Myc via AKT signaling, which contributes to cancer cell resistance to BET inhibitors in PC cellsHumans/cell lines/mice
ADAR1Coding geneA-to-I editing occurs in exon 12 of GLI1 mRNA, specifically at nucleotide position chr12:57864624GLI1, circNEIL3CircNEIL3 promotes the proliferation and metastasis of PC via the circNEIL3/miR-432-5p/ADAR1/GLI1/cell cycle and EMT axis and that its expression is negatively regulated by ADAR1 via a feedback loopHumans/cell lines/mice
Prostate cancerADAR1LncRNAADAR1 interacts with PRUNE2/PCA3 dsRNA and controls the levels of PRUNE2PCA3 and PRUNE2PCA3 as a transdominant negative oncogene that inhibits the unidentified tumor suppressor gene PRUNE2 at the RNA level through an ADAR-mediated mechanismHumans/cell lines/mice
Thyroid cancerADAR1MiRNAThe editing hotspot in miR-200b is located in its
seed region		miR-200bThe impaired ability of edited miR-200b to inhibit ZEB1 could promote motility and invasion in TC cellsHumans/cell lines/mice
ADAR1Coding gene (c.308A > G)p.Q103RCDK13Edited CDK13-Q103R stimulates a stronger cell proliferation and migration phenotype than WT CDK1Humans/cell lines
A-to-I suppressing cancer
Acute myeloid leukemiaADAR2Coding geneCOPA(p.I164V) COG3(p.I635V)COPA and COG3ADAR2 suppresses leukemogenesis specifically in t(8;21) and inv16 AML cells by the RUNX1-ETO AE9a fusion protein, targeting COPA and COG3 to inhibit clonogenic growth of human t(8;21) AML cellsHumans/cell lines/mice
Breast cancerADAR1Coding genep.I342MGABRA3Edited Gabra3 suppresses BC cell invasion and metastasisCell lines/mice
Colorectal cancerADAR2MiRNAADAR2 regulates the secretion of miR-200s or influences the levels of RBPs or other components of the miRNA secretion machinerymiR-200sPKCζ-phosphorylated ADAR2 promotes the accumulation of miR-200s and loss of the PKCζ/ADAR2 axis results in EMT and increased liver metastasesHumans/cell lines/mice
Esophageal squamous cell carcinomaADAR2Coding gene (c.284A > G)p.K95RIGFBP7ADAR2 edits and stabilizes IGFBP7 to suppresses tumor growth and induces apoptosis in ESCCHumans/cell lines/mice
Gastric cancerADAR2Coding genep.H241RPODXLEdited PODXL at codon 241 (His to Arg) confers a loss-of-function phenotype that neutralizes the tumorigenic ability of the unedited PODXLHumans/cell lines/mice
GlioblastomaADAR2MiRNAADAR2 reduces the levels of miR-221, -222 and -21 by preventing their precursors from maturing.miR-222/221 and miR-21ADAR2 edits miR-222/221 and miR-21 precursors and decreases the expression of the corresponding mature onco-miRNAs in vivo and in vitro, with significant effects on cell proliferation and migrationHumans/cell lines/mice
ADAR2IntronEdited CDC14B pre-mRNA enhances its expression and therefore reduces the skp2 target proteinCDC14BADAR2 inhibits astrocytoma growth by increasing the level of CDC14B, which in turn affects the Skp2/p21-p27 pathwayHumans/cell lines/mice
GliomaADAR2MiRNAThe A-to-I editing of miR-378a occurs within the seed regionmiR-376a*Unedited miR-376a* decreases RAP2A, but a modified miR-376a* causes an accumulation of AMFR, collectively leading to increased migration and invasiveness of glioma cellsHumans/cell lines/mice
ADAR3Coding genep.Q607RGRIA2Low expression of ADAR3 may induce unedited GRIA2 transcripts level that can promote cell migration and tumor invasionHumans/cell lines
Hepatocellular carcinomaADAR2SNPThe rs2253763 C-to-T change in ADAR2 3′UTR reduces
its interaction with miR-542-3p and allele-specifically elevates ADAR2 levels		rs2253763 genetic variantsThe rs2253763 SNP in ADAR2 3’-UTR could disturb miR-
542-3p binding, leading to dysregulated production of ADAR2 in an allelic way and ADAR2 could enhance oxaliplatin sensitivity		Humans/cell lines
ADAR2Coding genep.I164VCOPAHypo-editing of COPA (coatomer protein complex, subunit α) is closely linked to HCC pathogenesisHumans/cell lines/mice
MelanomaADAR1MiRNAADAR1 regulates biogenesis of miRNAs directly by potentially affecting Drosha complex and indirectly by regulating Dicer via let-7miR-17,
miR-432		Overexpression of miR-17-5p and miR-432 mediates the loss of ADAR1 in cancer cells and subsequently increases the malignant featuresHumans/cell lines/mice
ADAR1MiRNAThe reduction of ADAR1 results in aberrant miRNA processing, as well as alterations in the overall levels of mature miR-455-5pmiR-455-5pEdited miR-455-5p inhibits melanoma metastasis through promotion of the tumour suppressor gene CPEB1Cell lines/mice
ADAR1MiRNAEdited miR-22 regulates
the stability of the mRNA of ITGB3		ITGB3, miR-22 and PAX6ADAR1 regulates ITGB3 expression via miR-22 and PAX6 transcription factor both at the posttranscriptional and transcriptional levels, respectivelyHumans/cell lines
ADAR1MiRNAReduced miR-30a/d lead to a significant increase in ITGB3
expression in all three melanoma lines at the mRNA level		ITGB3, miR-30a and miR-30dADAR1 regulates ITGB3 by pointing on miR-30a and miR-30d as ADAR1-controlled microRNAs, which play a direct role in the posttranscriptional expression control of ITGB3 and of the invasive melanoma cell phenotypeHumans/cell lines/mice
ADAR1MiRNAADAR1 influences the transcription of miR222 precursorsmiR-222ADAR1 regulates the biogenesis of miR222 and thereby ICAM1 expression, which consequently affects melanoma immune resistanceHumans/cell lines
ADAR1MiRNAThe A-to-I editing of miR-378a-3p is non-canonical and it occurs outside the seed regionmiR-378a-3pEdited miR-378a-3p binds to the 3ʹ-UTR of the PARVA oncogene and inhibits its expression, thus preventing the progression of melanoma towards the malignant phenotypeCell lines/mice
Thyroid cancerADAR3SNPThe ADAR3 rs904957 polymorphism, which involves a thymine-to-cytosine (T-to-C) change in the 3′UTR, increases the binding affinity of miR-1180-3p and suppresses ADAR3rs904957 genetic variantsADAR3 rs904957 genetic polymorphism located in the gene 3’-UTR results in allelic downregulation of ADAR3 expression and miR-1180-3p posttranscriptionally suppresses ADARB2 expressionHumans/cell lines

NA: not available.

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