{"gene":"AZIN1","run_date":"2026-04-28T17:12:37","timeline":{"discoveries":[{"year":2013,"finding":"ADAR1-mediated A-to-I RNA editing of AZIN1 results in a serine-to-glycine substitution at residue 367 (S367G), causing a conformational change that induces cytoplasmic-to-nuclear translocation of AZIN1 protein, increases its binding affinity to antizyme, enhances AZIN1 protein stability, and promotes cell proliferation by neutralizing antizyme-mediated degradation of ODC and cyclin D1 (CCND1).","method":"Transcriptome sequencing, site-directed mutagenesis, Co-IP, subcellular fractionation/imaging, functional proliferation assays, in vivo tumor models","journal":"Nature medicine","confidence":"High","confidence_rationale":"Tier 1-2 — multiple orthogonal methods (sequencing, mutagenesis, binding assays, localization, in vivo), foundational paper with 445 citations replicated across subsequent studies","pmids":["23291631"],"is_preprint":false},{"year":2013,"finding":"AZIN1 splice variant 2 (AZIN1 SV2), whose expression is enhanced by an SNP that reduces SRp40 splicing factor activity, reduces collagen I and α-smooth muscle actin expression in hepatic stellate cells via a polyamine-independent pathway that does not interact with antizyme.","method":"Minigene splicing assay, shRNA knockdown of SRp40, transient transfection of AZIN1 SV2 cDNA, qRT-PCR and Western blot for fibrogenic markers","journal":"Hepatology (Baltimore, Md.)","confidence":"Medium","confidence_rationale":"Tier 2 — multiple methods in a single study with functional readout and mechanistic pathway placement","pmids":["21837750"],"is_preprint":false},{"year":2013,"finding":"miR-433, induced by Smad3 binding to the miR-433 promoter downstream of TGF-β signaling, targets AZIN1 to suppress its expression, thereby creating a positive feedback loop that amplifies TGF-β/Smad3-driven renal fibrosis; AZIN1 overexpression suppresses TGF-β signaling.","method":"Luciferase reporter assay for promoter binding, miR-433 overexpression/knockdown, AZIN1 overexpression, in vivo ultrasound microbubble gene delivery, Western blot","journal":"Kidney international","confidence":"Medium","confidence_rationale":"Tier 2 — reciprocal gain/loss-of-function with in vivo validation and promoter binding assay in single lab","pmids":["23868013"],"is_preprint":false},{"year":2021,"finding":"RNA editing of Azin1 (S367G) in hematopoietic stem and progenitor cells causes nuclear translocation of the edited AZIN1 protein and enhanced binding affinity to DDX1 (DEAD box polypeptide 1), altering the chromatin distribution of DDX1 and the expression of multiple hematopoietic regulators to promote HSPC differentiation.","method":"RNA sequencing of sorted murine hematopoietic cell populations, Co-IP/pulldown for DDX1 interaction, subcellular fractionation, chromatin distribution assays, functional differentiation assays","journal":"Blood","confidence":"High","confidence_rationale":"Tier 1-2 — multiple orthogonal methods (transcriptomics, protein interaction, chromatin, functional differentiation assays) in a single rigorous study","pmids":["34388251"],"is_preprint":false},{"year":2023,"finding":"RNA editing of AZIN1 coding sites is catalyzed exclusively by the cytoplasmic isoform ADAR1 p150 (not nuclear ADAR1 p110 or ADAR2) after splicing, by forming a dsRNA structure with a downstream exon in the mature mRNA; the intervening intron suppresses editing in pre-mRNA, and nuclear retention of ADAR1 p150 (by NES deletion) reduces editing levels.","method":"Adar1 p110/Adar2 double KO mice, Adar1 p150 KO mice, type I interferon treatment, precursor vs. mature mRNA editing analysis, NES deletion mutant of ADAR1 p150, editing quantification in Raw 264.7 and HEK293T cells","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 1 — genetic KO models combined with mutagenesis and mechanistic RNA structure analysis, replicated in multiple cell systems","pmids":["37209819"],"is_preprint":false},{"year":2022,"finding":"Edited AZIN1 (S367G) binds to alpha-smooth muscle actin (ACTA2), gamma actin 1 (ACTG1), and myosin9 — interactions absent with wild-type AZIN1 — and this binding to the actin/myosin9 complex enables nuclear translocation of edited AZIN1 and promotes tumor aggressiveness in prostate cancer.","method":"Protein interaction profiling (pulldown/MS), overexpression of edited vs. uneditable AZIN1 alleles, subcellular localization imaging, clinical specimen analysis","journal":"Experimental & molecular medicine","confidence":"Medium","confidence_rationale":"Tier 2 — differential binding identified by proteomics with functional localization follow-up, but single lab","pmids":["36202978"],"is_preprint":false},{"year":2022,"finding":"RNA-edited AZIN1 promotes tumor angiogenesis by delaying c-Myc degradation via an OAZ2-mediated ubiquitin-independent proteasome pathway, leading to increased mRNA expression and secretion of the angiogenic factor IL-8.","method":"In vitro angiogenesis assays, in vivo tumor models, IL-8 ELISA/qRT-PCR, c-Myc stability assays, OAZ2 manipulation","journal":"Cell death & disease","confidence":"Medium","confidence_rationale":"Tier 2 — in vitro and in vivo functional assays with mechanistic pathway placement, single lab","pmids":["35365616"],"is_preprint":false},{"year":2024,"finding":"AZIN1 A-to-I editing, triggered by preceding inflammation via ADAR1 isoform switching, enhances polyamine biosynthesis and also engages glycolysis and nicotinamide biosynthesis pathways to drive a kidney recovery phenotype, as demonstrated by genetically modified human cell lines and mice locked in edited or uneditable states.","method":"Genetically modified human cell lines and knock-in/knock-out mice (edited vs. uneditable AZIN1), metabolomics, RNA sequencing, murine endotoxemia model","journal":"The Journal of clinical investigation","confidence":"High","confidence_rationale":"Tier 1-2 — genetic lock-in models (edited vs. uneditable) combined with metabolomics and in vivo phenotyping in multiple orthogonal systems","pmids":["38954486"],"is_preprint":false},{"year":2025,"finding":"AZIN1 promotes osteosarcoma cell cycle progression and immune evasion through polyamine biosynthesis; AZIN1 knockdown reduces MYC expression, downregulates cell cycle genes, and alters immunomodulatory cytokine and HLA molecule expression, enhancing T-cell-mediated cytotoxicity.","method":"AZIN1 siRNA/shRNA knockdown, polyamine depletion experiments, TCR-engineered T-cell cytotoxicity assays, Western blot for MYC and cell cycle proteins, tumor growth models","journal":"Cell death & disease","confidence":"Medium","confidence_rationale":"Tier 2 — loss-of-function with defined molecular and functional readouts, single lab","pmids":["40246846"],"is_preprint":false},{"year":2018,"finding":"Edited AZIN1 (S367G) confers cancer stem cell properties and enhances metastatic potential in colorectal cancer cells; ADAR1-mediated editing is upregulated in CRC and drives oncogenic gain-of-function phenotypes.","method":"AZIN1 edited vs. wild-type expression in CRC cell lines, stemness assays, in vivo metastasis models, patient cohort analysis","journal":"JCI insight","confidence":"Medium","confidence_rationale":"Tier 2 — functional assays with edited vs. WT constructs and in vivo validation, single lab","pmids":["29925690"],"is_preprint":false},{"year":2025,"finding":"AZIN1 overexpression in medulloblastoma cells increases binding and inhibition of antizyme, which prevents antizyme-mediated deactivation of c-Myc, resulting in increased MYC activity and a more aggressive tumor phenotype; CRISPR-Cas9 knockout of AZIN1 reduced tumor progression in orthotopic mouse models.","method":"CRISPR-Cas9 AZIN1 knockout, orthotopic implantation in nude mice, IVIS imaging, Western blot, invasion/colony formation/proliferation assays","journal":"Journal of experimental & clinical cancer research : CR","confidence":"Medium","confidence_rationale":"Tier 2 — CRISPR KO with in vivo and in vitro functional readouts, single lab","pmids":["39962590"],"is_preprint":false}],"current_model":"AZIN1 (antizyme inhibitor 1) functions as a positive regulator of polyamine biosynthesis by binding and inhibiting antizyme, thereby preventing antizyme-mediated proteasomal degradation of ODC and other growth-promoting proteins (cyclin D1, c-Myc); critically, ADAR1 p150-catalyzed A-to-I RNA editing of AZIN1 after splicing introduces an S367G substitution that induces cytoplasmic-to-nuclear translocation (mediated by binding to an actin/myosin9 complex or DDX1), increases antizyme binding affinity, enhances protein stability, activates additional biosynthetic programs (glycolysis, nicotinamide biosynthesis), and confers gain-of-function oncogenic and stem-cell phenotypes across multiple cancer types."},"narrative":{"teleology":[{"year":2013,"claim":"The discovery that ADAR1-mediated A-to-I editing of AZIN1 produces an S367G substitution that alters protein conformation, localization, antizyme-binding affinity, and stability established AZIN1 RNA editing as a functionally consequential oncogenic event and defined the core biochemical mechanism by which edited AZIN1 neutralizes antizyme-mediated degradation of ODC and cyclin D1.","evidence":"Transcriptome sequencing, site-directed mutagenesis, Co-IP, subcellular fractionation, in vivo tumor models in hepatocellular carcinoma","pmids":["23291631"],"confidence":"High","gaps":["The enzyme isoform responsible for AZIN1 editing (p110 vs. p150) and the timing relative to splicing were not resolved","Mechanism of nuclear translocation of edited AZIN1 was not identified","Whether edited AZIN1 has nuclear functions beyond antizyme sequestration was unknown"]},{"year":2013,"claim":"Parallel work identified an AZIN1 splice variant (SV2) that suppresses fibrogenic markers through a polyamine-independent, antizyme-independent pathway, and showed that AZIN1 overexpression antagonizes TGF-β/Smad3 signaling in renal fibrosis, revealing non-canonical roles for AZIN1 outside polyamine regulation.","evidence":"Minigene splicing assays, shRNA knockdown, AZIN1 overexpression in hepatic stellate cells and kidney fibrosis models with in vivo gene delivery","pmids":["21837750","23868013"],"confidence":"Medium","gaps":["The polyamine-independent mechanism of AZIN1 SV2 action on fibrogenic genes is undefined","Whether the anti-fibrotic splice variant and the edited form interact or compete is unknown","Findings are from single laboratories without independent replication"]},{"year":2018,"claim":"Demonstrating that edited AZIN1 confers cancer stem-cell properties and enhanced metastatic potential in colorectal cancer extended the oncogenic editing paradigm beyond proliferation to stemness and invasion.","evidence":"Edited vs. wild-type AZIN1 expression in CRC cell lines, stemness assays, in vivo metastasis models, patient cohort analysis","pmids":["29925690"],"confidence":"Medium","gaps":["Downstream transcriptional programs driven by edited AZIN1 in stem cells were not identified","Whether stem-cell phenotypes depend on nuclear AZIN1 or cytoplasmic antizyme inhibition was not distinguished"]},{"year":2021,"claim":"Identification of DDX1 as a nuclear binding partner of edited AZIN1 in hematopoietic stem/progenitor cells, with consequent alteration of DDX1 chromatin distribution and hematopoietic gene expression, established a non-canonical nuclear mechanism for edited AZIN1 independent of polyamine biosynthesis.","evidence":"Co-IP/pulldown, subcellular fractionation, chromatin distribution assays, functional differentiation assays in sorted murine hematopoietic populations","pmids":["34388251"],"confidence":"High","gaps":["Direct genomic targets of the AZIN1–DDX1 complex are not mapped","Whether DDX1-mediated chromatin remodeling also operates in cancer contexts is untested"]},{"year":2022,"claim":"Proteomic identification of ACTA2, ACTG1, and myosin9 as editing-specific interactors of AZIN1 provided a molecular mechanism for the cytoplasmic-to-nuclear translocation of edited AZIN1, while parallel work showed that edited AZIN1 stabilizes c-Myc via OAZ2 to drive angiogenesis through IL-8 secretion.","evidence":"Pulldown/mass spectrometry for interaction profiling; c-Myc stability and IL-8 expression assays with OAZ2 manipulation; in vivo tumor angiogenesis models","pmids":["36202978","35365616"],"confidence":"Medium","gaps":["Whether actin/myosin9 transport and DDX1 binding represent sequential or alternative nuclear import mechanisms is unresolved","The relative contribution of OAZ1 vs. OAZ2 in different tissues has not been systematically compared","Findings from single laboratories"]},{"year":2023,"claim":"Genetic dissection using isoform-specific knockout mice proved that AZIN1 coding-site editing is catalyzed exclusively by cytoplasmic ADAR1 p150 acting on spliced mRNA, resolving the enzyme identity and substrate timing questions left open by the original editing discovery.","evidence":"Adar1 p110/Adar2 double KO mice, Adar1 p150 KO mice, interferon treatment, NES deletion mutants, pre-mRNA vs. mRNA editing quantification","pmids":["37209819"],"confidence":"High","gaps":["The dsRNA structure formed by downstream exon that enables editing has not been structurally resolved","How inflammation-induced ADAR1 isoform switching quantitatively tunes editing levels remains incompletely characterized"]},{"year":2024,"claim":"Metabolomic and genetic lock-in studies revealed that edited AZIN1 activates glycolysis and nicotinamide biosynthesis in addition to polyamine synthesis, broadening the metabolic scope of AZIN1 editing beyond the polyamine pathway and linking it to kidney injury recovery.","evidence":"Genetically modified human cell lines and knock-in mice locked in edited or uneditable AZIN1 states, metabolomics, RNA sequencing, murine endotoxemia model","pmids":["38954486"],"confidence":"High","gaps":["The molecular mechanism by which AZIN1 engages glycolytic and NAD+ biosynthetic enzymes is unknown","Whether these metabolic effects operate through antizyme inhibition or a distinct mechanism is unresolved"]},{"year":2025,"claim":"CRISPR knockout and knockdown studies in osteosarcoma and medulloblastoma demonstrated that AZIN1 sustains MYC protein levels and promotes cell cycle progression, immune evasion, and tumor aggressiveness through polyamine-dependent antizyme inhibition, consolidating its role as a druggable oncogenic node.","evidence":"CRISPR-Cas9 KO with orthotopic mouse models; siRNA/shRNA knockdown with TCR-engineered T-cell cytotoxicity assays and polyamine depletion experiments","pmids":["40246846","39962590"],"confidence":"Medium","gaps":["Whether therapeutic targeting of AZIN1 is feasible without disrupting normal polyamine homeostasis is untested","The mechanism by which AZIN1/polyamines regulate HLA expression and immune evasion is not defined","Findings are from single laboratories"]},{"year":null,"claim":"Key unresolved questions include the structural basis of the S367G conformational change, whether the nuclear functions of edited AZIN1 (DDX1 interaction, chromatin remodeling) operate through antizyme-dependent or -independent mechanisms, and whether AZIN1 editing can be therapeutically modulated without disrupting normal ADAR1 function.","evidence":"","pmids":[],"confidence":"Low","gaps":["No crystal or cryo-EM structure of wild-type or edited AZIN1 exists","The relationship between antizyme-dependent and antizyme-independent nuclear functions has not been dissected","No pharmacological tool compounds targeting AZIN1 or its editing have been reported"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0098772","term_label":"molecular function regulator activity","supporting_discovery_ids":[0,6,8,10]}],"localization":[{"term_id":"GO:0005829","term_label":"cytosol","supporting_discovery_ids":[0,5]},{"term_id":"GO:0005634","term_label":"nucleus","supporting_discovery_ids":[0,3,5]}],"pathway":[{"term_id":"R-HSA-1430728","term_label":"Metabolism","supporting_discovery_ids":[0,7,8]},{"term_id":"R-HSA-392499","term_label":"Metabolism of proteins","supporting_discovery_ids":[0,6,10]},{"term_id":"R-HSA-1640170","term_label":"Cell Cycle","supporting_discovery_ids":[8,10]},{"term_id":"R-HSA-1643685","term_label":"Disease","supporting_discovery_ids":[6,9,10]}],"complexes":[],"partners":["OAZ1","OAZ2","DDX1","MYH9","ACTG1","ACTA2","ODC1","ADAR"],"other_free_text":[]},"mechanistic_narrative":"AZIN1 is a central positive regulator of polyamine biosynthesis and cell proliferation that functions by binding and sequestering antizyme, thereby preventing antizyme-mediated proteasomal degradation of ornithine decarboxylase (ODC), cyclin D1, and c-Myc [PMID:23291631, PMID:39962590, PMID:40246846]. ADAR1 p150 catalyzes A-to-I RNA editing of AZIN1 mRNA after splicing, introducing an S367G substitution that increases antizyme-binding affinity, enhances protein stability, and triggers cytoplasmic-to-nuclear translocation via interaction with an actin/myosin9 complex or DDX1, enabling nuclear functions including chromatin remodeling of hematopoietic regulators [PMID:37209819, PMID:36202978, PMID:34388251]. Edited AZIN1 acts as a gain-of-function oncogene across multiple cancer types by stabilizing c-Myc to promote angiogenesis, conferring cancer stem-cell properties, driving immune evasion, and activating glycolysis and nicotinamide biosynthesis pathways beyond canonical polyamine production [PMID:35365616, PMID:29925690, PMID:38954486, PMID:40246846]. AZIN1 also participates in anti-fibrotic signaling: a polyamine-independent splice variant suppresses fibrogenic markers in hepatic stellate cells, and AZIN1 overexpression antagonizes TGF-β/Smad3-driven renal fibrosis [PMID:21837750, PMID:23868013]."},"prefetch_data":{"uniprot":{"accession":"O14977","full_name":"Antizyme inhibitor 1","aliases":["Ornithine decarboxylase antizyme inhibitor"],"length_aa":448,"mass_kda":49.5,"function":"Antizyme inhibitor (AZI) protein that positively regulates ornithine decarboxylase (ODC) activity and polyamine uptake. AZI is an enzymatically inactive ODC homolog that counteracts the negative effect of ODC antizymes (AZs) OAZ1, OAZ2 and OAZ3 on ODC activity by competing with ODC for antizyme-binding (PubMed:17900240, PubMed:26305948). Inhibits antizyme-dependent ODC degradation and releases ODC monomers from their inactive complex with antizymes, leading to formation of the catalytically active ODC homodimer and restoring polyamine production (PubMed:17900240)","subcellular_location":"Nucleus","url":"https://www.uniprot.org/uniprotkb/O14977/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/AZIN1","classification":"Not Classified","n_dependent_lines":105,"n_total_lines":1208,"dependency_fraction":0.0869205298013245},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/AZIN1","total_profiled":1310},"omim":[{"mim_id":"608353","title":"ANTIZYME INHIBITOR 2; AZIN2","url":"https://www.omim.org/entry/608353"},{"mim_id":"607909","title":"ANTIZYME INHIBITOR 1; AZIN1","url":"https://www.omim.org/entry/607909"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Approved","locations":[{"location":"Nucleoli","reliability":"Approved"},{"location":"Nucleoli rim","reliability":"Approved"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/AZIN1"},"hgnc":{"alias_symbol":["OAZI","ODC1L"],"prev_symbol":["OAZIN"]},"alphafold":{"accession":"O14977","domains":[{"cath_id":"2.40.37.10","chopping":"9-38_281-384_388-403","consensus_level":"high","plddt":85.7905,"start":9,"end":403},{"cath_id":"3.20.20.10","chopping":"46-275","consensus_level":"high","plddt":93.1801,"start":46,"end":275}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/O14977","model_url":"https://alphafold.ebi.ac.uk/files/AF-O14977-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-O14977-F1-predicted_aligned_error_v6.png","plddt_mean":88.31},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=AZIN1","jax_strain_url":"https://www.jax.org/strain/search?query=AZIN1"},"sequence":{"accession":"O14977","fasta_url":"https://rest.uniprot.org/uniprotkb/O14977.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/O14977/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/O14977"}},"corpus_meta":[{"pmid":"23291631","id":"PMC_23291631","title":"Recoding RNA editing of AZIN1 predisposes to hepatocellular carcinoma.","date":"2013","source":"Nature medicine","url":"https://pubmed.ncbi.nlm.nih.gov/23291631","citation_count":445,"is_preprint":false},{"pmid":"23868013","id":"PMC_23868013","title":"The microRNA miR-433 promotes renal fibrosis by amplifying the TGF-β/Smad3-Azin1 pathway.","date":"2013","source":"Kidney international","url":"https://pubmed.ncbi.nlm.nih.gov/23868013","citation_count":140,"is_preprint":false},{"pmid":"29925690","id":"PMC_29925690","title":"AZIN1 RNA editing confers cancer stemness and enhances oncogenic potential in colorectal cancer.","date":"2018","source":"JCI insight","url":"https://pubmed.ncbi.nlm.nih.gov/29925690","citation_count":107,"is_preprint":false},{"pmid":"30583079","id":"PMC_30583079","title":"Activation of AZIN1 RNA editing is a novel mechanism that promotes invasive potential of cancer-associated fibroblasts in colorectal cancer.","date":"2018","source":"Cancer letters","url":"https://pubmed.ncbi.nlm.nih.gov/30583079","citation_count":55,"is_preprint":false},{"pmid":"28849733","id":"PMC_28849733","title":"RNA editing of AZIN1 induces the malignant progression of non-small-cell lung cancers.","date":"2017","source":"Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine","url":"https://pubmed.ncbi.nlm.nih.gov/28849733","citation_count":50,"is_preprint":false},{"pmid":"34388251","id":"PMC_34388251","title":"A comprehensive RNA editome reveals that edited Azin1 partners with DDX1 to enable hematopoietic stem cell differentiation.","date":"2021","source":"Blood","url":"https://pubmed.ncbi.nlm.nih.gov/34388251","citation_count":34,"is_preprint":false},{"pmid":"35365616","id":"PMC_35365616","title":"A novel mechanism for A-to-I RNA-edited AZIN1 in promoting tumor angiogenesis in colorectal cancer.","date":"2022","source":"Cell death & disease","url":"https://pubmed.ncbi.nlm.nih.gov/35365616","citation_count":33,"is_preprint":false},{"pmid":"21837750","id":"PMC_21837750","title":"A polymorphism that delays fibrosis in hepatitis C promotes alternative splicing of AZIN1, reducing fibrogenesis.","date":"2011","source":"Hepatology (Baltimore, Md.)","url":"https://pubmed.ncbi.nlm.nih.gov/21837750","citation_count":24,"is_preprint":false},{"pmid":"35697535","id":"PMC_35697535","title":"ADAR1 and AZIN1 RNA editing function as an oncogene and contributes to immortalization in endometrial cancer.","date":"2022","source":"Gynecologic oncology","url":"https://pubmed.ncbi.nlm.nih.gov/35697535","citation_count":19,"is_preprint":false},{"pmid":"33116570","id":"PMC_33116570","title":"AZIN1-AS1, A Novel Oncogenic LncRNA, Promotes the Progression of Non-Small Cell Lung Cancer by Regulating MiR-513b-5p and DUSP11.","date":"2020","source":"OncoTargets and therapy","url":"https://pubmed.ncbi.nlm.nih.gov/33116570","citation_count":16,"is_preprint":false},{"pmid":"28315656","id":"PMC_28315656","title":"Expression of ODC1, SPD, SPM and AZIN1 in the hypothalamus, ovary and uterus during rat estrous cycle.","date":"2017","source":"General and comparative endocrinology","url":"https://pubmed.ncbi.nlm.nih.gov/28315656","citation_count":16,"is_preprint":false},{"pmid":"37104086","id":"PMC_37104086","title":"ADAR1 affects gastric cancer cell metastasis and reverses cisplatin resistance through AZIN1.","date":"2023","source":"Anti-cancer drugs","url":"https://pubmed.ncbi.nlm.nih.gov/37104086","citation_count":13,"is_preprint":false},{"pmid":"37209819","id":"PMC_37209819","title":"RNA editing of AZIN1 coding sites is catalyzed by ADAR1 p150 after splicing.","date":"2023","source":"The Journal of biological 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Animal","url":"https://pubmed.ncbi.nlm.nih.gov/35064471","citation_count":12,"is_preprint":false},{"pmid":"36202978","id":"PMC_36202978","title":"AZIN1 RNA editing alters protein interactions, leading to nuclear translocation and worse outcomes in prostate cancer.","date":"2022","source":"Experimental & molecular medicine","url":"https://pubmed.ncbi.nlm.nih.gov/36202978","citation_count":11,"is_preprint":false},{"pmid":"38954486","id":"PMC_38954486","title":"Inflammation primes the murine kidney for recovery by activating AZIN1 adenosine-to-inosine editing.","date":"2024","source":"The Journal of clinical investigation","url":"https://pubmed.ncbi.nlm.nih.gov/38954486","citation_count":9,"is_preprint":false},{"pmid":"40246846","id":"PMC_40246846","title":"AZIN1-dependent polyamine synthesis accelerates tumor cell cycle progression and impairs effector T-cell function in osteosarcoma.","date":"2025","source":"Cell death & disease","url":"https://pubmed.ncbi.nlm.nih.gov/40246846","citation_count":5,"is_preprint":false},{"pmid":"39962590","id":"PMC_39962590","title":"AZIN1 level is increased in medulloblastoma and correlates with c-Myc activity and tumor phenotype.","date":"2025","source":"Journal of experimental & clinical cancer research : CR","url":"https://pubmed.ncbi.nlm.nih.gov/39962590","citation_count":4,"is_preprint":false},{"pmid":"36700468","id":"PMC_36700468","title":"Long non-coding RNA MALAT1 aggravated liver ischemia-reperfusion injury via targeting miR-150-5p/AZIN1.","date":"2022","source":"Bioengineered","url":"https://pubmed.ncbi.nlm.nih.gov/36700468","citation_count":4,"is_preprint":false},{"pmid":"38767730","id":"PMC_38767730","title":"Ame-miR-1-3p of bee venom reduced cell viability through the AZIN1/OAZ1-ODC1-polyamines pathway and enhanced the defense ability of honeybee (Apis mellifera L.).","date":"2024","source":"Insect molecular biology","url":"https://pubmed.ncbi.nlm.nih.gov/38767730","citation_count":3,"is_preprint":false},{"pmid":"39453997","id":"PMC_39453997","title":"Toxoplasma gondii macrophage migration inhibitory factor shows anti-Mycobacterium tuberculosis potential via AZIN1/STAT1 interaction.","date":"2024","source":"Science advances","url":"https://pubmed.ncbi.nlm.nih.gov/39453997","citation_count":2,"is_preprint":false},{"pmid":"37986799","id":"PMC_37986799","title":"Inflammation primes the kidney for recovery by activating AZIN1 A-to-I editing.","date":"2023","source":"bioRxiv : the preprint server for biology","url":"https://pubmed.ncbi.nlm.nih.gov/37986799","citation_count":0,"is_preprint":false},{"pmid":"23475882","id":"PMC_23475882","title":"Recoding RNA editing of AZIN1 is oncogenic in hepatocellular carcinoma.","date":"2013","source":"Cancer discovery","url":"https://pubmed.ncbi.nlm.nih.gov/23475882","citation_count":0,"is_preprint":false},{"pmid":null,"id":"bio_10.1101_2025.02.19.25322572","title":"Genetics of cardiovascular outcomes in individuals with chronic kidney disease: the Chronic Renal Insufficiency Cohort (CRIC) study","date":"2025-02-21","source":"bioRxiv","url":"https://doi.org/10.1101/2025.02.19.25322572","citation_count":0,"is_preprint":true}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":13770,"output_tokens":2854,"usd":0.04206},"stage2":{"model":"claude-opus-4-6","input_tokens":6205,"output_tokens":2879,"usd":0.1545},"total_usd":0.19656,"stage1_batch_id":"msgbatch_01TqNM6p6FsoMBT2jzQTwKBr","stage2_batch_id":"msgbatch_01Ya473eco8sTHbvRymQaU8o","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2013,\n      \"finding\": \"ADAR1-mediated A-to-I RNA editing of AZIN1 results in a serine-to-glycine substitution at residue 367 (S367G), causing a conformational change that induces cytoplasmic-to-nuclear translocation of AZIN1 protein, increases its binding affinity to antizyme, enhances AZIN1 protein stability, and promotes cell proliferation by neutralizing antizyme-mediated degradation of ODC and cyclin D1 (CCND1).\",\n      \"method\": \"Transcriptome sequencing, site-directed mutagenesis, Co-IP, subcellular fractionation/imaging, functional proliferation assays, in vivo tumor models\",\n      \"journal\": \"Nature medicine\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 — multiple orthogonal methods (sequencing, mutagenesis, binding assays, localization, in vivo), foundational paper with 445 citations replicated across subsequent studies\",\n      \"pmids\": [\"23291631\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"AZIN1 splice variant 2 (AZIN1 SV2), whose expression is enhanced by an SNP that reduces SRp40 splicing factor activity, reduces collagen I and α-smooth muscle actin expression in hepatic stellate cells via a polyamine-independent pathway that does not interact with antizyme.\",\n      \"method\": \"Minigene splicing assay, shRNA knockdown of SRp40, transient transfection of AZIN1 SV2 cDNA, qRT-PCR and Western blot for fibrogenic markers\",\n      \"journal\": \"Hepatology (Baltimore, Md.)\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — multiple methods in a single study with functional readout and mechanistic pathway placement\",\n      \"pmids\": [\"21837750\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"miR-433, induced by Smad3 binding to the miR-433 promoter downstream of TGF-β signaling, targets AZIN1 to suppress its expression, thereby creating a positive feedback loop that amplifies TGF-β/Smad3-driven renal fibrosis; AZIN1 overexpression suppresses TGF-β signaling.\",\n      \"method\": \"Luciferase reporter assay for promoter binding, miR-433 overexpression/knockdown, AZIN1 overexpression, in vivo ultrasound microbubble gene delivery, Western blot\",\n      \"journal\": \"Kidney international\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — reciprocal gain/loss-of-function with in vivo validation and promoter binding assay in single lab\",\n      \"pmids\": [\"23868013\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"RNA editing of Azin1 (S367G) in hematopoietic stem and progenitor cells causes nuclear translocation of the edited AZIN1 protein and enhanced binding affinity to DDX1 (DEAD box polypeptide 1), altering the chromatin distribution of DDX1 and the expression of multiple hematopoietic regulators to promote HSPC differentiation.\",\n      \"method\": \"RNA sequencing of sorted murine hematopoietic cell populations, Co-IP/pulldown for DDX1 interaction, subcellular fractionation, chromatin distribution assays, functional differentiation assays\",\n      \"journal\": \"Blood\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 — multiple orthogonal methods (transcriptomics, protein interaction, chromatin, functional differentiation assays) in a single rigorous study\",\n      \"pmids\": [\"34388251\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"RNA editing of AZIN1 coding sites is catalyzed exclusively by the cytoplasmic isoform ADAR1 p150 (not nuclear ADAR1 p110 or ADAR2) after splicing, by forming a dsRNA structure with a downstream exon in the mature mRNA; the intervening intron suppresses editing in pre-mRNA, and nuclear retention of ADAR1 p150 (by NES deletion) reduces editing levels.\",\n      \"method\": \"Adar1 p110/Adar2 double KO mice, Adar1 p150 KO mice, type I interferon treatment, precursor vs. mature mRNA editing analysis, NES deletion mutant of ADAR1 p150, editing quantification in Raw 264.7 and HEK293T cells\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 — genetic KO models combined with mutagenesis and mechanistic RNA structure analysis, replicated in multiple cell systems\",\n      \"pmids\": [\"37209819\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"Edited AZIN1 (S367G) binds to alpha-smooth muscle actin (ACTA2), gamma actin 1 (ACTG1), and myosin9 — interactions absent with wild-type AZIN1 — and this binding to the actin/myosin9 complex enables nuclear translocation of edited AZIN1 and promotes tumor aggressiveness in prostate cancer.\",\n      \"method\": \"Protein interaction profiling (pulldown/MS), overexpression of edited vs. uneditable AZIN1 alleles, subcellular localization imaging, clinical specimen analysis\",\n      \"journal\": \"Experimental & molecular medicine\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — differential binding identified by proteomics with functional localization follow-up, but single lab\",\n      \"pmids\": [\"36202978\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"RNA-edited AZIN1 promotes tumor angiogenesis by delaying c-Myc degradation via an OAZ2-mediated ubiquitin-independent proteasome pathway, leading to increased mRNA expression and secretion of the angiogenic factor IL-8.\",\n      \"method\": \"In vitro angiogenesis assays, in vivo tumor models, IL-8 ELISA/qRT-PCR, c-Myc stability assays, OAZ2 manipulation\",\n      \"journal\": \"Cell death & disease\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — in vitro and in vivo functional assays with mechanistic pathway placement, single lab\",\n      \"pmids\": [\"35365616\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"AZIN1 A-to-I editing, triggered by preceding inflammation via ADAR1 isoform switching, enhances polyamine biosynthesis and also engages glycolysis and nicotinamide biosynthesis pathways to drive a kidney recovery phenotype, as demonstrated by genetically modified human cell lines and mice locked in edited or uneditable states.\",\n      \"method\": \"Genetically modified human cell lines and knock-in/knock-out mice (edited vs. uneditable AZIN1), metabolomics, RNA sequencing, murine endotoxemia model\",\n      \"journal\": \"The Journal of clinical investigation\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 — genetic lock-in models (edited vs. uneditable) combined with metabolomics and in vivo phenotyping in multiple orthogonal systems\",\n      \"pmids\": [\"38954486\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"AZIN1 promotes osteosarcoma cell cycle progression and immune evasion through polyamine biosynthesis; AZIN1 knockdown reduces MYC expression, downregulates cell cycle genes, and alters immunomodulatory cytokine and HLA molecule expression, enhancing T-cell-mediated cytotoxicity.\",\n      \"method\": \"AZIN1 siRNA/shRNA knockdown, polyamine depletion experiments, TCR-engineered T-cell cytotoxicity assays, Western blot for MYC and cell cycle proteins, tumor growth models\",\n      \"journal\": \"Cell death & disease\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — loss-of-function with defined molecular and functional readouts, single lab\",\n      \"pmids\": [\"40246846\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"Edited AZIN1 (S367G) confers cancer stem cell properties and enhances metastatic potential in colorectal cancer cells; ADAR1-mediated editing is upregulated in CRC and drives oncogenic gain-of-function phenotypes.\",\n      \"method\": \"AZIN1 edited vs. wild-type expression in CRC cell lines, stemness assays, in vivo metastasis models, patient cohort analysis\",\n      \"journal\": \"JCI insight\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — functional assays with edited vs. WT constructs and in vivo validation, single lab\",\n      \"pmids\": [\"29925690\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"AZIN1 overexpression in medulloblastoma cells increases binding and inhibition of antizyme, which prevents antizyme-mediated deactivation of c-Myc, resulting in increased MYC activity and a more aggressive tumor phenotype; CRISPR-Cas9 knockout of AZIN1 reduced tumor progression in orthotopic mouse models.\",\n      \"method\": \"CRISPR-Cas9 AZIN1 knockout, orthotopic implantation in nude mice, IVIS imaging, Western blot, invasion/colony formation/proliferation assays\",\n      \"journal\": \"Journal of experimental & clinical cancer research : CR\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — CRISPR KO with in vivo and in vitro functional readouts, single lab\",\n      \"pmids\": [\"39962590\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"AZIN1 (antizyme inhibitor 1) functions as a positive regulator of polyamine biosynthesis by binding and inhibiting antizyme, thereby preventing antizyme-mediated proteasomal degradation of ODC and other growth-promoting proteins (cyclin D1, c-Myc); critically, ADAR1 p150-catalyzed A-to-I RNA editing of AZIN1 after splicing introduces an S367G substitution that induces cytoplasmic-to-nuclear translocation (mediated by binding to an actin/myosin9 complex or DDX1), increases antizyme binding affinity, enhances protein stability, activates additional biosynthetic programs (glycolysis, nicotinamide biosynthesis), and confers gain-of-function oncogenic and stem-cell phenotypes across multiple cancer types.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"AZIN1 is a central positive regulator of polyamine biosynthesis and cell proliferation that functions by binding and sequestering antizyme, thereby preventing antizyme-mediated proteasomal degradation of ornithine decarboxylase (ODC), cyclin D1, and c-Myc [PMID:23291631, PMID:39962590, PMID:40246846]. ADAR1 p150 catalyzes A-to-I RNA editing of AZIN1 mRNA after splicing, introducing an S367G substitution that increases antizyme-binding affinity, enhances protein stability, and triggers cytoplasmic-to-nuclear translocation via interaction with an actin/myosin9 complex or DDX1, enabling nuclear functions including chromatin remodeling of hematopoietic regulators [PMID:37209819, PMID:36202978, PMID:34388251]. Edited AZIN1 acts as a gain-of-function oncogene across multiple cancer types by stabilizing c-Myc to promote angiogenesis, conferring cancer stem-cell properties, driving immune evasion, and activating glycolysis and nicotinamide biosynthesis pathways beyond canonical polyamine production [PMID:35365616, PMID:29925690, PMID:38954486, PMID:40246846]. AZIN1 also participates in anti-fibrotic signaling: a polyamine-independent splice variant suppresses fibrogenic markers in hepatic stellate cells, and AZIN1 overexpression antagonizes TGF-β/Smad3-driven renal fibrosis [PMID:21837750, PMID:23868013].\",\n  \"teleology\": [\n    {\n      \"year\": 2013,\n      \"claim\": \"The discovery that ADAR1-mediated A-to-I editing of AZIN1 produces an S367G substitution that alters protein conformation, localization, antizyme-binding affinity, and stability established AZIN1 RNA editing as a functionally consequential oncogenic event and defined the core biochemical mechanism by which edited AZIN1 neutralizes antizyme-mediated degradation of ODC and cyclin D1.\",\n      \"evidence\": \"Transcriptome sequencing, site-directed mutagenesis, Co-IP, subcellular fractionation, in vivo tumor models in hepatocellular carcinoma\",\n      \"pmids\": [\"23291631\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"The enzyme isoform responsible for AZIN1 editing (p110 vs. p150) and the timing relative to splicing were not resolved\",\n        \"Mechanism of nuclear translocation of edited AZIN1 was not identified\",\n        \"Whether edited AZIN1 has nuclear functions beyond antizyme sequestration was unknown\"\n      ]\n    },\n    {\n      \"year\": 2013,\n      \"claim\": \"Parallel work identified an AZIN1 splice variant (SV2) that suppresses fibrogenic markers through a polyamine-independent, antizyme-independent pathway, and showed that AZIN1 overexpression antagonizes TGF-β/Smad3 signaling in renal fibrosis, revealing non-canonical roles for AZIN1 outside polyamine regulation.\",\n      \"evidence\": \"Minigene splicing assays, shRNA knockdown, AZIN1 overexpression in hepatic stellate cells and kidney fibrosis models with in vivo gene delivery\",\n      \"pmids\": [\"21837750\", \"23868013\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"The polyamine-independent mechanism of AZIN1 SV2 action on fibrogenic genes is undefined\",\n        \"Whether the anti-fibrotic splice variant and the edited form interact or compete is unknown\",\n        \"Findings are from single laboratories without independent replication\"\n      ]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Demonstrating that edited AZIN1 confers cancer stem-cell properties and enhanced metastatic potential in colorectal cancer extended the oncogenic editing paradigm beyond proliferation to stemness and invasion.\",\n      \"evidence\": \"Edited vs. wild-type AZIN1 expression in CRC cell lines, stemness assays, in vivo metastasis models, patient cohort analysis\",\n      \"pmids\": [\"29925690\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Downstream transcriptional programs driven by edited AZIN1 in stem cells were not identified\",\n        \"Whether stem-cell phenotypes depend on nuclear AZIN1 or cytoplasmic antizyme inhibition was not distinguished\"\n      ]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Identification of DDX1 as a nuclear binding partner of edited AZIN1 in hematopoietic stem/progenitor cells, with consequent alteration of DDX1 chromatin distribution and hematopoietic gene expression, established a non-canonical nuclear mechanism for edited AZIN1 independent of polyamine biosynthesis.\",\n      \"evidence\": \"Co-IP/pulldown, subcellular fractionation, chromatin distribution assays, functional differentiation assays in sorted murine hematopoietic populations\",\n      \"pmids\": [\"34388251\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Direct genomic targets of the AZIN1–DDX1 complex are not mapped\",\n        \"Whether DDX1-mediated chromatin remodeling also operates in cancer contexts is untested\"\n      ]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Proteomic identification of ACTA2, ACTG1, and myosin9 as editing-specific interactors of AZIN1 provided a molecular mechanism for the cytoplasmic-to-nuclear translocation of edited AZIN1, while parallel work showed that edited AZIN1 stabilizes c-Myc via OAZ2 to drive angiogenesis through IL-8 secretion.\",\n      \"evidence\": \"Pulldown/mass spectrometry for interaction profiling; c-Myc stability and IL-8 expression assays with OAZ2 manipulation; in vivo tumor angiogenesis models\",\n      \"pmids\": [\"36202978\", \"35365616\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Whether actin/myosin9 transport and DDX1 binding represent sequential or alternative nuclear import mechanisms is unresolved\",\n        \"The relative contribution of OAZ1 vs. OAZ2 in different tissues has not been systematically compared\",\n        \"Findings from single laboratories\"\n      ]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Genetic dissection using isoform-specific knockout mice proved that AZIN1 coding-site editing is catalyzed exclusively by cytoplasmic ADAR1 p150 acting on spliced mRNA, resolving the enzyme identity and substrate timing questions left open by the original editing discovery.\",\n      \"evidence\": \"Adar1 p110/Adar2 double KO mice, Adar1 p150 KO mice, interferon treatment, NES deletion mutants, pre-mRNA vs. mRNA editing quantification\",\n      \"pmids\": [\"37209819\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"The dsRNA structure formed by downstream exon that enables editing has not been structurally resolved\",\n        \"How inflammation-induced ADAR1 isoform switching quantitatively tunes editing levels remains incompletely characterized\"\n      ]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Metabolomic and genetic lock-in studies revealed that edited AZIN1 activates glycolysis and nicotinamide biosynthesis in addition to polyamine synthesis, broadening the metabolic scope of AZIN1 editing beyond the polyamine pathway and linking it to kidney injury recovery.\",\n      \"evidence\": \"Genetically modified human cell lines and knock-in mice locked in edited or uneditable AZIN1 states, metabolomics, RNA sequencing, murine endotoxemia model\",\n      \"pmids\": [\"38954486\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"The molecular mechanism by which AZIN1 engages glycolytic and NAD+ biosynthetic enzymes is unknown\",\n        \"Whether these metabolic effects operate through antizyme inhibition or a distinct mechanism is unresolved\"\n      ]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"CRISPR knockout and knockdown studies in osteosarcoma and medulloblastoma demonstrated that AZIN1 sustains MYC protein levels and promotes cell cycle progression, immune evasion, and tumor aggressiveness through polyamine-dependent antizyme inhibition, consolidating its role as a druggable oncogenic node.\",\n      \"evidence\": \"CRISPR-Cas9 KO with orthotopic mouse models; siRNA/shRNA knockdown with TCR-engineered T-cell cytotoxicity assays and polyamine depletion experiments\",\n      \"pmids\": [\"40246846\", \"39962590\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Whether therapeutic targeting of AZIN1 is feasible without disrupting normal polyamine homeostasis is untested\",\n        \"The mechanism by which AZIN1/polyamines regulate HLA expression and immune evasion is not defined\",\n        \"Findings are from single laboratories\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"Key unresolved questions include the structural basis of the S367G conformational change, whether the nuclear functions of edited AZIN1 (DDX1 interaction, chromatin remodeling) operate through antizyme-dependent or -independent mechanisms, and whether AZIN1 editing can be therapeutically modulated without disrupting normal ADAR1 function.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No crystal or cryo-EM structure of wild-type or edited AZIN1 exists\",\n        \"The relationship between antizyme-dependent and antizyme-independent nuclear functions has not been dissected\",\n        \"No pharmacological tool compounds targeting AZIN1 or its editing have been reported\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0098772\", \"supporting_discovery_ids\": [0, 6, 8, 10]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005829\", \"supporting_discovery_ids\": [0, 5]},\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [0, 3, 5]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-1430728\", \"supporting_discovery_ids\": [0, 7, 8]},\n      {\"term_id\": \"R-HSA-392499\", \"supporting_discovery_ids\": [0, 6, 10]},\n      {\"term_id\": \"R-HSA-1640170\", \"supporting_discovery_ids\": [8, 10]},\n      {\"term_id\": \"R-HSA-1643685\", \"supporting_discovery_ids\": [6, 9, 10]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\n      \"OAZ1\",\n      \"OAZ2\",\n      \"DDX1\",\n      \"MYH9\",\n      \"ACTG1\",\n      \"ACTA2\",\n      \"ODC1\",\n      \"ADAR\"\n    ],\n    \"other_free_text\": []\n  }\n}\n```"}