{"gene":"MIER3","run_date":"2026-06-10T02:59:50","timeline":{"discoveries":[{"year":2017,"finding":"MIER3 is predominantly a nuclear protein, as determined by confocal microscopy analysis.","method":"Confocal immunofluorescence microscopy","journal":"PloS one","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — direct localization experiment replicated across cell lines in single study, but no functional consequence directly linked to nuclear localization","pmids":["28046085"],"is_preprint":false},{"year":2017,"finding":"MIER3 does not recruit HDAC1 or HDAC2, and MIER3 complexes have no associated deacetylase activity, in contrast to MIER1 and MIER2. This was demonstrated across HEK293, MCF7, and HeLa cell lines.","method":"Co-immunoprecipitation and histone deacetylase activity assay","journal":"PloS one","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — two orthogonal methods (Co-IP and enzymatic assay), tested across multiple cell lines, single lab — negative result robustly established","pmids":["28046085"],"is_preprint":false},{"year":2017,"finding":"MIER3 does not form homodimers or heterodimers with MIER1 or MIER2, as shown by co-immunoprecipitation.","method":"Co-immunoprecipitation","journal":"PloS one","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — single Co-IP method, tested across multiple cell lines and MIER family members in single lab","pmids":["28046085"],"is_preprint":false},{"year":2021,"finding":"MIER3 interacts with HDAC1, HDAC2, and Snail to form a transcriptional co-repressor complex that binds the E-cadherin promoter, leading to histone deacetylation and silencing of E-cadherin, thereby promoting epithelial-mesenchymal transition (EMT) in breast cancer cells.","method":"Co-immunoprecipitation, immunofluorescence, chromatin immunoprecipitation (ChIP) assay, Western blot","journal":"Experimental cell research","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — multiple orthogonal methods (Co-IP, ChIP, IF, WB) in single lab; note apparent contradiction with PMID:28046085 which found MIER3 does not recruit HDACs — confidence tempered by inter-study discrepancy","pmids":["34242623"],"is_preprint":false},{"year":2017,"finding":"MIER3 overexpression inhibits colorectal cancer cell proliferation, migration, and invasion in vitro and represses tumor growth and metastasis in vivo, acting at least partly through reduction of Sp1 protein levels and subsequent suppression of EMT.","method":"Cell proliferation assay, migration/invasion assay, xenograft mouse model, Western blot (Sp1 and EMT markers)","journal":"Scientific reports","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — in vitro and in vivo loss/gain-of-function with defined molecular readout (Sp1 reduction), single lab with multiple assays","pmids":["28887525"],"is_preprint":false},{"year":2020,"finding":"MIER3 overexpression suppresses NSCLC cell proliferation, migration, and invasion, and inhibits the Wnt/β-catenin signaling pathway. Additionally, MIER3 decreases the histone acetyltransferase (HAT) activity of p300 in NSCLC cells.","method":"MTT assay, wound-healing assay, Transwell invasion assay, Western blot, flow cytometry, HAT activity assay, xenograft mouse model","journal":"Translational cancer research","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single lab, multiple assays but HAT inhibition mechanism not biochemically dissected; abstract does not detail direct interaction between MIER3 and p300","pmids":["35117188"],"is_preprint":false}],"current_model":"MIER3 is a predominantly nuclear ELM2-SANT domain protein that, unlike its paralog MIER1, does not constitutively recruit HDAC1/2 or exhibit deacetylase activity in standard cell lines; however, in breast cancer contexts it has been reported to form a co-repressor complex with HDAC1/HDAC2 and Snail to silence E-cadherin and promote EMT, while in colorectal and lung cancer contexts it acts as a tumor suppressor by reducing Sp1 levels, suppressing EMT, and inhibiting Wnt/β-catenin signaling and p300 HAT activity."},"narrative":{"mechanistic_narrative":"MIER3 is a predominantly nuclear ELM2-SANT family protein implicated in transcriptional repression and the control of epithelial-mesenchymal transition (EMT) in cancer [PMID:28046085, PMID:28887525]. Unlike its paralogs MIER1 and MIER2, MIER3 does not constitutively recruit HDAC1 or HDAC2 and its complexes carry no associated deacetylase activity in HEK293, MCF7, and HeLa cells, nor does it homodimerize or heterodimerize with other MIER family members [PMID:28046085]. In a breast cancer context, MIER3 assembles a co-repressor complex with HDAC1, HDAC2, and Snail that binds the E-cadherin promoter and drives its histone-deacetylation-dependent silencing, promoting EMT [PMID:34242623]. In colorectal cancer, MIER3 instead acts as a tumor suppressor, inhibiting proliferation, migration, invasion, and xenograft growth and metastasis through reduction of Sp1 protein levels and consequent suppression of EMT [PMID:28887525]. In non-small-cell lung cancer, MIER3 overexpression suppresses proliferation and invasion, inhibits Wnt/β-catenin signaling, and decreases the histone acetyltransferase activity of p300 [PMID:35117188]. The opposing co-repressor and tumor-suppressor roles reported across tissue contexts are not reconciled mechanistically in the available corpus.","teleology":[{"year":2017,"claim":"Establishing where MIER3 acts and whether it shares the HDAC-recruiting co-repressor activity of its paralogs was needed to place it within the MIER family; the data localized it to the nucleus but showed it diverges functionally from MIER1/MIER2.","evidence":"Confocal immunofluorescence, Co-IP, and HDAC activity assays across HEK293, MCF7, and HeLa cells","pmids":["28046085"],"confidence":"Medium","gaps":["No identification of which transcriptional partners or chromatin marks MIER3 does engage","Negative HDAC result was obtained in standard cell lines, not cancer-specific contexts","No functional consequence directly linked to nuclear localization"]},{"year":2017,"claim":"Whether MIER3 influences tumor behavior was unknown; gain-of-function experiments established it as a suppressor of colorectal cancer growth and metastasis acting through Sp1 reduction and EMT suppression.","evidence":"Proliferation, migration/invasion assays, xenograft mouse model, and Western blot of Sp1 and EMT markers","pmids":["28887525"],"confidence":"Medium","gaps":["Mechanism by which MIER3 lowers Sp1 protein levels is undefined","No direct physical interaction with Sp1 demonstrated","Does not address contexts where MIER3 is oncogenic"]},{"year":2020,"claim":"The pathway through which MIER3 restrains lung cancer was unclear; data linked it to Wnt/β-catenin inhibition and reduced p300 HAT activity, extending its tumor-suppressor role to NSCLC.","evidence":"MTT, wound-healing, Transwell, flow cytometry, HAT activity assay, and xenograft model in NSCLC cells","pmids":["35117188"],"confidence":"Low","gaps":["HAT inhibition mechanism not biochemically dissected and direct MIER3-p300 interaction not shown","Link between Wnt/β-catenin inhibition and p300 activity not established","Single-lab study"]},{"year":2021,"claim":"Contrary to the earlier negative HDAC result and the tumor-suppressor role, this work showed MIER3 can form an HDAC1/HDAC2/Snail co-repressor complex that silences E-cadherin to drive EMT in breast cancer, defining an oncogenic, context-dependent activity.","evidence":"Co-IP, ChIP, immunofluorescence, and Western blot in breast cancer cells","pmids":["34242623"],"confidence":"Medium","gaps":["Directly contradicts the 2017 finding that MIER3 does not recruit HDAC1/2; discrepancy unresolved","Whether HDAC recruitment is cell-type-specific or condition-dependent is unknown","No structural basis for the differential complex assembly"]},{"year":null,"claim":"How MIER3 switches between an HDAC-recruiting oncogenic co-repressor and a Sp1/p300/Wnt-modulating tumor suppressor across tissues remains unresolved.","evidence":"","pmids":[],"confidence":"Low","gaps":["No mechanistic reconciliation of context-dependent HDAC recruitment","No structural or domain-level basis for partner selection","Direct binding partners beyond Snail/HDACs not mapped"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0140110","term_label":"transcription regulator activity","supporting_discovery_ids":[3,4]}],"localization":[{"term_id":"GO:0005634","term_label":"nucleus","supporting_discovery_ids":[0]}],"pathway":[{"term_id":"R-HSA-74160","term_label":"Gene expression (Transcription)","supporting_discovery_ids":[3]}],"complexes":[],"partners":["HDAC1","HDAC2","SNAI1"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q7Z3K6","full_name":"Mesoderm induction early response protein 3","aliases":[],"length_aa":550,"mass_kda":61.4,"function":"Transcriptional repressor","subcellular_location":"Nucleus","url":"https://www.uniprot.org/uniprotkb/Q7Z3K6/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/MIER3","classification":"Not Classified","n_dependent_lines":10,"n_total_lines":1208,"dependency_fraction":0.008278145695364239},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[{"gene":"HDAC1","stoichiometry":0.2},{"gene":"HDAC2","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/search/MIER3","total_profiled":1310},"omim":[{"mim_id":"620100","title":"MIER FAMILY, MEMBER 3; MIER3","url":"https://www.omim.org/entry/620100"},{"mim_id":"620092","title":"MIER FAMILY, MEMBER 2; MIER2","url":"https://www.omim.org/entry/620092"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Enhanced","locations":[{"location":"Nucleoplasm","reliability":"Enhanced"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/MIER3"},"hgnc":{"alias_symbol":["FLJ35954","DKFZp686L09111","DKFZp781I1119"],"prev_symbol":[]},"alphafold":{"accession":"Q7Z3K6","domains":[{"cath_id":"-","chopping":"214-271","consensus_level":"high","plddt":79.2302,"start":214,"end":271},{"cath_id":"1.10.10.60","chopping":"280-339","consensus_level":"medium","plddt":90.0443,"start":280,"end":339}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q7Z3K6","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q7Z3K6-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q7Z3K6-F1-predicted_aligned_error_v6.png","plddt_mean":57.94},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=MIER3","jax_strain_url":"https://www.jax.org/strain/search?query=MIER3"},"sequence":{"accession":"Q7Z3K6","fasta_url":"https://rest.uniprot.org/uniprotkb/Q7Z3K6.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q7Z3K6/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q7Z3K6"}},"corpus_meta":[{"pmid":"28046085","id":"PMC_28046085","title":"Differential HDAC1 and 2 Recruitment by Members of the MIER Family.","date":"2017","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/28046085","citation_count":26,"is_preprint":false},{"pmid":"28887525","id":"PMC_28887525","title":"MIER3 suppresses colorectal cancer progression by down-regulating Sp1, inhibiting epithelial-mesenchymal transition.","date":"2017","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/28887525","citation_count":25,"is_preprint":false},{"pmid":"22993404","id":"PMC_22993404","title":"Rat Mcs1b is concordant to the genome-wide association-identified breast cancer risk locus at human 5q11.2 and MIER3 is a candidate cancer susceptibility gene.","date":"2012","source":"Cancer research","url":"https://pubmed.ncbi.nlm.nih.gov/22993404","citation_count":22,"is_preprint":false},{"pmid":"34242623","id":"PMC_34242623","title":"MIER3 induces epithelial-mesenchymal transition and promotes breast cancer cell aggressiveness via forming a co-repressor complex with HDAC1/HDAC2/Snail.","date":"2021","source":"Experimental cell research","url":"https://pubmed.ncbi.nlm.nih.gov/34242623","citation_count":18,"is_preprint":false},{"pmid":"32922197","id":"PMC_32922197","title":"Characterization and functional prediction of the microRNAs differentially expressed in a mouse model of concanavalin A-induced autoimmune hepatitis.","date":"2020","source":"International journal of medical sciences","url":"https://pubmed.ncbi.nlm.nih.gov/32922197","citation_count":14,"is_preprint":false},{"pmid":"26740066","id":"PMC_26740066","title":"Does mouse embryo primordial germ cell activation start before implantation as suggested by single-cell transcriptomics dynamics?","date":"2016","source":"Molecular human reproduction","url":"https://pubmed.ncbi.nlm.nih.gov/26740066","citation_count":14,"is_preprint":false},{"pmid":"33584805","id":"PMC_33584805","title":"Breed Ancestry, Divergence, Admixture, and Selection Patterns of the Simbra Crossbreed.","date":"2021","source":"Frontiers in genetics","url":"https://pubmed.ncbi.nlm.nih.gov/33584805","citation_count":9,"is_preprint":false},{"pmid":"35117188","id":"PMC_35117188","title":"MIER3 suppresses the progression of non-small cell lung cancer by inhibiting Wnt/β-Catenin pathway and histone acetyltransferase activity.","date":"2020","source":"Translational cancer research","url":"https://pubmed.ncbi.nlm.nih.gov/35117188","citation_count":5,"is_preprint":false},{"pmid":"38444510","id":"PMC_38444510","title":"Transcriptome analysis provides insights into high fat diet-induced kidney injury and moderate intensity continuous training-mediated protective effects.","date":"2024","source":"Heliyon","url":"https://pubmed.ncbi.nlm.nih.gov/38444510","citation_count":3,"is_preprint":false},{"pmid":"35129549","id":"PMC_35129549","title":"Erratum to MIER3 suppresses the progression of non-small cell lung cancer by inhibiting Wnt/β-Catenin pathway and histone acetyltransferase activity.","date":"2020","source":"Translational cancer research","url":"https://pubmed.ncbi.nlm.nih.gov/35129549","citation_count":0,"is_preprint":false},{"pmid":"37240242","id":"PMC_37240242","title":"Preliminary Study on Expression and Function of the Chicken W Chromosome Gene MIER3 in Embryonic Gonads.","date":"2023","source":"International journal of molecular sciences","url":"https://pubmed.ncbi.nlm.nih.gov/37240242","citation_count":0,"is_preprint":false},{"pmid":"40973823","id":"PMC_40973823","title":"Identification and functional analysis of Rattus norvegicus Mammary carcinoma susceptibility 1b (Mcs1b) nominated variants.","date":"2025","source":"Mammalian genome : official journal of the International Mammalian Genome Society","url":"https://pubmed.ncbi.nlm.nih.gov/40973823","citation_count":0,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":9186,"output_tokens":1373,"usd":0.024077,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":8023,"output_tokens":2046,"usd":0.045632,"stage2_stop_reason":"end_turn"},"total_usd":0.069709,"stage1_batch_id":"msgbatch_01BbTCMyrRPyhtEq6b1MdwCN","stage2_batch_id":"msgbatch_011dEed5bbxYvTAaQWKJevxu","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2017,\n      \"finding\": \"MIER3 is predominantly a nuclear protein, as determined by confocal microscopy analysis.\",\n      \"method\": \"Confocal immunofluorescence microscopy\",\n      \"journal\": \"PloS one\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — direct localization experiment replicated across cell lines in single study, but no functional consequence directly linked to nuclear localization\",\n      \"pmids\": [\"28046085\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"MIER3 does not recruit HDAC1 or HDAC2, and MIER3 complexes have no associated deacetylase activity, in contrast to MIER1 and MIER2. This was demonstrated across HEK293, MCF7, and HeLa cell lines.\",\n      \"method\": \"Co-immunoprecipitation and histone deacetylase activity assay\",\n      \"journal\": \"PloS one\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — two orthogonal methods (Co-IP and enzymatic assay), tested across multiple cell lines, single lab — negative result robustly established\",\n      \"pmids\": [\"28046085\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"MIER3 does not form homodimers or heterodimers with MIER1 or MIER2, as shown by co-immunoprecipitation.\",\n      \"method\": \"Co-immunoprecipitation\",\n      \"journal\": \"PloS one\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — single Co-IP method, tested across multiple cell lines and MIER family members in single lab\",\n      \"pmids\": [\"28046085\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"MIER3 interacts with HDAC1, HDAC2, and Snail to form a transcriptional co-repressor complex that binds the E-cadherin promoter, leading to histone deacetylation and silencing of E-cadherin, thereby promoting epithelial-mesenchymal transition (EMT) in breast cancer cells.\",\n      \"method\": \"Co-immunoprecipitation, immunofluorescence, chromatin immunoprecipitation (ChIP) assay, Western blot\",\n      \"journal\": \"Experimental cell research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — multiple orthogonal methods (Co-IP, ChIP, IF, WB) in single lab; note apparent contradiction with PMID:28046085 which found MIER3 does not recruit HDACs — confidence tempered by inter-study discrepancy\",\n      \"pmids\": [\"34242623\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"MIER3 overexpression inhibits colorectal cancer cell proliferation, migration, and invasion in vitro and represses tumor growth and metastasis in vivo, acting at least partly through reduction of Sp1 protein levels and subsequent suppression of EMT.\",\n      \"method\": \"Cell proliferation assay, migration/invasion assay, xenograft mouse model, Western blot (Sp1 and EMT markers)\",\n      \"journal\": \"Scientific reports\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — in vitro and in vivo loss/gain-of-function with defined molecular readout (Sp1 reduction), single lab with multiple assays\",\n      \"pmids\": [\"28887525\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"MIER3 overexpression suppresses NSCLC cell proliferation, migration, and invasion, and inhibits the Wnt/β-catenin signaling pathway. Additionally, MIER3 decreases the histone acetyltransferase (HAT) activity of p300 in NSCLC cells.\",\n      \"method\": \"MTT assay, wound-healing assay, Transwell invasion assay, Western blot, flow cytometry, HAT activity assay, xenograft mouse model\",\n      \"journal\": \"Translational cancer research\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, multiple assays but HAT inhibition mechanism not biochemically dissected; abstract does not detail direct interaction between MIER3 and p300\",\n      \"pmids\": [\"35117188\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"MIER3 is a predominantly nuclear ELM2-SANT domain protein that, unlike its paralog MIER1, does not constitutively recruit HDAC1/2 or exhibit deacetylase activity in standard cell lines; however, in breast cancer contexts it has been reported to form a co-repressor complex with HDAC1/HDAC2 and Snail to silence E-cadherin and promote EMT, while in colorectal and lung cancer contexts it acts as a tumor suppressor by reducing Sp1 levels, suppressing EMT, and inhibiting Wnt/β-catenin signaling and p300 HAT activity.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"MIER3 is a predominantly nuclear ELM2-SANT family protein implicated in transcriptional repression and the control of epithelial-mesenchymal transition (EMT) in cancer [#0, #4]. Unlike its paralogs MIER1 and MIER2, MIER3 does not constitutively recruit HDAC1 or HDAC2 and its complexes carry no associated deacetylase activity in HEK293, MCF7, and HeLa cells, nor does it homodimerize or heterodimerize with other MIER family members [#1, #2]. In a breast cancer context, MIER3 assembles a co-repressor complex with HDAC1, HDAC2, and Snail that binds the E-cadherin promoter and drives its histone-deacetylation-dependent silencing, promoting EMT [#3]. In colorectal cancer, MIER3 instead acts as a tumor suppressor, inhibiting proliferation, migration, invasion, and xenograft growth and metastasis through reduction of Sp1 protein levels and consequent suppression of EMT [#4]. In non-small-cell lung cancer, MIER3 overexpression suppresses proliferation and invasion, inhibits Wnt/\\u03b2-catenin signaling, and decreases the histone acetyltransferase activity of p300 [#5]. The opposing co-repressor and tumor-suppressor roles reported across tissue contexts are not reconciled mechanistically in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2017,\n      \"claim\": \"Establishing where MIER3 acts and whether it shares the HDAC-recruiting co-repressor activity of its paralogs was needed to place it within the MIER family; the data localized it to the nucleus but showed it diverges functionally from MIER1/MIER2.\",\n      \"evidence\": \"Confocal immunofluorescence, Co-IP, and HDAC activity assays across HEK293, MCF7, and HeLa cells\",\n      \"pmids\": [\"28046085\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No identification of which transcriptional partners or chromatin marks MIER3 does engage\",\n        \"Negative HDAC result was obtained in standard cell lines, not cancer-specific contexts\",\n        \"No functional consequence directly linked to nuclear localization\"\n      ]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"Whether MIER3 influences tumor behavior was unknown; gain-of-function experiments established it as a suppressor of colorectal cancer growth and metastasis acting through Sp1 reduction and EMT suppression.\",\n      \"evidence\": \"Proliferation, migration/invasion assays, xenograft mouse model, and Western blot of Sp1 and EMT markers\",\n      \"pmids\": [\"28887525\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Mechanism by which MIER3 lowers Sp1 protein levels is undefined\",\n        \"No direct physical interaction with Sp1 demonstrated\",\n        \"Does not address contexts where MIER3 is oncogenic\"\n      ]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"The pathway through which MIER3 restrains lung cancer was unclear; data linked it to Wnt/\\u03b2-catenin inhibition and reduced p300 HAT activity, extending its tumor-suppressor role to NSCLC.\",\n      \"evidence\": \"MTT, wound-healing, Transwell, flow cytometry, HAT activity assay, and xenograft model in NSCLC cells\",\n      \"pmids\": [\"35117188\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"HAT inhibition mechanism not biochemically dissected and direct MIER3-p300 interaction not shown\",\n        \"Link between Wnt/\\u03b2-catenin inhibition and p300 activity not established\",\n        \"Single-lab study\"\n      ]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Contrary to the earlier negative HDAC result and the tumor-suppressor role, this work showed MIER3 can form an HDAC1/HDAC2/Snail co-repressor complex that silences E-cadherin to drive EMT in breast cancer, defining an oncogenic, context-dependent activity.\",\n      \"evidence\": \"Co-IP, ChIP, immunofluorescence, and Western blot in breast cancer cells\",\n      \"pmids\": [\"34242623\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Directly contradicts the 2017 finding that MIER3 does not recruit HDAC1/2; discrepancy unresolved\",\n        \"Whether HDAC recruitment is cell-type-specific or condition-dependent is unknown\",\n        \"No structural basis for the differential complex assembly\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How MIER3 switches between an HDAC-recruiting oncogenic co-repressor and a Sp1/p300/Wnt-modulating tumor suppressor across tissues remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No mechanistic reconciliation of context-dependent HDAC recruitment\",\n        \"No structural or domain-level basis for partner selection\",\n        \"Direct binding partners beyond Snail/HDACs not mapped\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0140110\", \"supporting_discovery_ids\": [3, 4]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-74160\", \"supporting_discovery_ids\": [3]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"HDAC1\", \"HDAC2\", \"SNAI1\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"faith_supported":3,"faith_total":5,"faith_pct":60.0}}