Affinage

RUNX3

Runt-related transcription factor 3 · UniProt Q13761

Length
415 aa
Mass
44.4 kDa
Annotated
2026-06-10
100 papers in source corpus 37 papers cited in narrative 37 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

RUNX3 is a runt-domain DNA-binding transcription factor that acts as a context-dependent tumor suppressor and master regulator of immune-cell differentiation, operating downstream of TGF-β signaling to restrain proliferation and promote apoptosis in epithelial cells (PMID:11955451). Its transcriptional control depends on direct, sequence-specific promoter binding, with the Runt-domain mutation R122C abolishing both DNA binding and tumor-suppressive function (PMID:11955451, PMID:24636883). RUNX3 engages target genes bidirectionally: it activates growth-restraining and pro-apoptotic programs—inducing p21 within a transient pRb/Brd2 complex at the G1-S restriction point (PMID:28846108), inhibiting survivin (PMID:24636883), and driving apoptotic/ferroptotic outputs through SOD3 repression and ING1 activation (PMID:30692634, PMID:37156453)—while repressing targets such as Osterix, CD36, ICAM-3, and survivin (PMID:17352693, PMID:16887969, PMID:22479382, PMID:24636883). It additionally restrains oncogenic signaling by ubiquitinating GLI1 to suppress Hedgehog output (PMID:31278361), serving as an endpoint effector of MST/Hippo-mediated cell death (PMID:21678419), and interacting with YAP to limit its oncogenic activity (PMID:29581836). In the immune system, RUNX3 is a determinant of CD8 lineage commitment and CD4 repression in thymopoiesis (PMID:12796513), programs CD8+ tissue-resident memory identity by promoting residency genes and suppressing egress genes (PMID:29211713), and cooperates with ETS and T-box factors at enhancers to drive NK-cell activation programs (PMID:24421391, PMID:24236182). RUNX3 function is tuned post-translationally—Src-mediated tyrosine phosphorylation drives cytoplasmic mislocalization and inactivation (PMID:20100835), and hypoxic G9a-mediated lysine methylation reduces CBFβ/p300 interaction and nuclear import (PMID:33116296)—and transcriptionally, being silenced by Nr4a1/CoREST and AML fusion proteins yet upregulated by MYC in certain lymphomas (PMID:25762306, PMID:18663147, PMID:28119527). Beyond its tumor-suppressive role, context-specific gain of RUNX3 in Tet2-deficient progenitors suppresses Runx1 targets and activates Myc targets to drive MDS-like transformation (PMID:32341038).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 1999 Medium

    Established RUNX3 as a nuclear-matrix-associated serine phosphoprotein in hematopoietic cells whose expression is inducible, defining it as a regulated nuclear factor rather than a constitutive housekeeping protein.

    Evidence Western blot, nuclear fractionation, and pharmacological induction with retinoid receptor-selective ligands in hematopoietic cells

    PMID:10419474

    Open questions at the time
    • Did not define target genes or DNA-binding activity
    • Mechanism linking RARα signaling to RUNX3 induction not resolved
  2. 2002 High

    Defined RUNX3 as a TGF-β effector and tumor suppressor in gastric epithelium, answering whether RUNX3 loss is causal for proliferation/apoptosis dysregulation and establishing the Runt-domain dependence of its function.

    Evidence Runx3 knockout mice, TGF-β response assays, nude-mouse tumorigenicity, and R122C site-directed mutagenesis

    PMID:11955451

    Open questions at the time
    • Direct transcriptional targets mediating growth inhibition not identified
    • Cofactor requirements for TGF-β coupling unresolved
  3. 2003 High

    Showed RUNX3 (with RUNX1) is a transcriptional repressor of CD4 required for CD8 lineage commitment, defining its non-redundant and partially redundant roles in thymic T-cell fate.

    Evidence Runx3 knockout and compound Runx3/Runx1 mutant mice, flow cytometry, cytotoxicity assays

    PMID:12796513

    Open questions at the time
    • Direct CD4-silencer binding by RUNX3 not mapped in this study
    • Division of labor between RUNX1 and RUNX3 sites unresolved
  4. 2006 Medium

    Demonstrated direct repressive promoter occupancy on myeloid and developmental targets (CD36) and a requirement in DETC development, generalizing RUNX3 as a sequence-specific repressor beyond epithelium.

    Evidence EMSA, ChIP, reporter assays, and Runx3 knockout mice with flow cytometry

    PMID:16887969 PMID:17222403

    Open questions at the time
    • Cofactor specificity at distinct promoters not fully resolved
    • Activator vs repressor switch determinants unknown
  5. 2007 Medium

    Mapped direct DNA-binding repression of Osterix and a physical interaction with Ku70/Ku80 that modulates p21 transactivation, linking RUNX3 to both differentiation control and a DNA-repair-protein partner.

    Evidence EMSA, ChIP, site-directed mutagenesis, affinity purification/MS, domain-mapped pull-down and Co-IP

    PMID:17352693 PMID:17488194 PMID:17662272

    Open questions at the time
    • Functional consequence of Ku70 interaction in vivo unclear
    • Whether RUNX3 acts in DNA repair directly not established
  6. 2010 High

    Identified Src-mediated tyrosine phosphorylation as a post-translational inactivation mechanism causing cytoplasmic mislocalization, explaining how RUNX3 tumor-suppressor function is silenced without genetic loss.

    Evidence Src overexpression, Co-IP, siRNA knockdown, kinase inhibition, and subcellular fractionation in gastric/breast cancer cells

    PMID:20100835

    Open questions at the time
    • Specific phosphorylated tyrosine residues and import machinery affected not fully defined
    • In vivo prevalence in tumors not quantified
  7. 2012 Medium

    Positioned RUNX3 as an endpoint effector of MST/Hippo-mediated cell death and a direct repressor of ICAM-3, integrating it into apoptotic signaling and macrophage differentiation.

    Evidence Reciprocal Co-IP with SAV1/MST2, siRNA, cell-death assays, ChIP and reporter assays

    PMID:21678419 PMID:22479382

    Open questions at the time
    • Whether RUNX3 transcriptional output mediates Hippo-induced death not mapped
    • MST2 modification of RUNX3 not defined
  8. 2013 High

    Provided genome-wide evidence that RUNX3 binds RUNX/ETS-motif enhancers overlapping T-bet/p300 sites in CD8+ T and NK cells, defining its enhancer-level cooperativity and activation-expandable target set.

    Evidence ChIP-seq and transcriptome comparison of wild-type vs Runx3-/- primary cells; TSP-1 promoter binding in melanoma

    PMID:23846726 PMID:24236182

    Open questions at the time
    • Causal cofactor hierarchy at shared enhancers not dissected
    • Direct vs indirect targets within the expanded set not separated
  9. 2014 High

    Established RUNX3 cooperation with ETS/T-box factors driving IL-15-dependent NK-cell maturation and demonstrated DNA-binding-dependent repression of survivin, refining both immune and tumor-suppressive mechanisms.

    Evidence Runx3 knockout mice, ChIP-seq, RNA-seq, in vivo NK quantification; ChIP/reporter with R122C mutagenesis; Co-IP with EWS/FLI

    PMID:24421391 PMID:24636883 PMID:24812032

    Open questions at the time
    • Mechanism of EWS/FLI sequestration of RUNX3 not fully resolved
    • Direct uNK target genes not enumerated
  10. 2015 High

    Defined transcriptional silencing of RUNX3 by Nr4a1/CoREST in CD8+ T cells and a developmental requirement in osteoblast proliferation, expanding both its upstream regulation and tissue-specific roles.

    Evidence Nr4a1 knockout mice with ChIP; osteoblast-specific conditional knockout with histomorphometry and transcriptome

    PMID:25605327 PMID:25762306

    Open questions at the time
    • Direct osteoblast target genes not fully mapped
    • Link between Nr4a1 repression and lineage outcomes incomplete
  11. 2017 High

    Showed RUNX3 programs CD8+ tissue-resident memory identity and acts at the G1-S restriction point in a pRb/Brd2/p21 complex, while loss promotes oxidative-damage-driven senescence—unifying its immune, cell-cycle, and tumor-suppressive functions.

    Evidence In vivo RNAi screen, conditional KO and overexpression, ATAC-seq; Co-IP three-protein complex reconstitution; HO-1/DSB/senescence assays; miR-182/HOXA9 axis ChIP and reporter

    PMID:28846108 PMID:29054094 PMID:29074538 PMID:29211713

    Open questions at the time
    • Dynamics of pRb/Brd2 complex assembly across cell types not generalized
    • Direct vs indirect contribution to residency gene network unresolved
  12. 2019 Medium

    Extended RUNX3's anti-oncogenic repertoire to direct GLI1 ubiquitination (Hedgehog suppression) and YAP inhibition, and to sensory-neuron identity maintenance, broadening its mechanistic range beyond classical transcription.

    Evidence Co-IP and ubiquitination assays; interaction-dependent YAP functional assays; conditional Runx3 inactivation in PSNs with electrophysiology

    PMID:29581836 PMID:31278361 PMID:31575648

    Open questions at the time
    • Whether GLI1 ubiquitination is RUNX3-intrinsic or scaffold-dependent unclear
    • NT3-to-RUNX3 maintenance signaling pathway not detailed
  13. 2020 High

    Defined hypoxic G9a-mediated lysine methylation of RUNX3 (K129/K171) as an inactivation switch reducing CBFβ/p300 binding and import, and revealed an oncogenic gain-of-function context where RUNX3 drives MDS-like transformation in Tet2-deficient progenitors.

    Evidence In vitro methylation assays with mutagenesis, Co-IP, immunofluorescence; RUNX3-overexpressing Tet2-deficient mouse model with ChIP-seq/RNA-seq

    PMID:32341038 PMID:33116296

    Open questions at the time
    • Determinants of tumor-suppressor vs oncogenic context-switching not resolved
    • Reversibility of K-methylation in vivo not quantified
  14. 2021 High

    Resolved the overlapping yet functionally distinct RUNX1/RUNX3 binding landscape during T-lineage commitment, clarifying redundancy and site-shifting that underlie their collaborative gene-regulatory program.

    Evidence Single and double Runx CRISPR knockouts, stage-specific ChIP-seq and RNA-seq

    PMID:33479171

    Open questions at the time
    • Cofactors driving site-shifting not fully identified
    • Generality beyond T-progenitors untested
  15. 2023 Medium

    Added new tissue-specific functions—endothelial RUNX3 loss driving paracrine liver fibrosis, ferroptosis induction via ING1/SLC7A11, articular cartilage maintenance via lubricin/aggrecan, and vagal sensory-neuron control of esophageal peristalsis—demonstrating broad organ-level roles.

    Evidence Endothelial- and chondrocyte-specific knockout mice, scRNA-seq, adenoviral rescue, ChIP/reporter ferroptosis assays, optogenetics and genetic ablation

    PMID:36261443 PMID:37156453 PMID:37192624 PMID:39042837

    Open questions at the time
    • Direct vs indirect transcriptional targets in each tissue not fully separated
    • Shared regulatory logic across these contexts not unified

Open questions

Synthesis pass · forward-looking unresolved questions
  • What molecular determinants switch RUNX3 between tumor-suppressive and oncogenic transcriptional output, and how its post-translational modifications, cofactor availability, and genomic site selection are integrated in a given cell state, remains unresolved.
  • No unifying model for context-dependent activation vs repression
  • Structural basis of CBFβ/p300 vs G9a competition undefined
  • In vivo dynamics of the pRb/Brd2/RUNX3 cell-cycle complex unresolved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 6 GO:0003677 DNA binding 5
Localization
GO:0005634 nucleus 3 GO:0005829 cytosol 1
Pathway
R-HSA-1266738 Developmental Biology 5 R-HSA-168256 Immune System 5 R-HSA-162582 Signal Transduction 4 R-HSA-5357801 Programmed Cell Death 4 R-HSA-74160 Gene expression (Transcription) 4 R-HSA-1640170 Cell Cycle 1
Partners
BRD2CBFBEP300G9A (EHMT2)RB1SRCXRCC6 (KU70)YAP1
Complex memberships
RUNX3-pRb-Brd2 R-point complex

Evidence

Reading pass · 37 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2002 RUNX3 is a downstream effector of TGF-β signaling in gastric epithelial cells; Runx3-null mouse gastric mucosa shows hyperplasia due to stimulated proliferation and suppressed apoptosis with resistance to TGF-β growth-inhibitory and apoptosis-inducing actions. A Runt-domain mutation (R122C) abolishes tumor-suppressive function. Runx3 knockout mice, primary culture TGF-β response assays, nude mouse tumorigenicity assay, site-directed mutagenesis Cell High 11955451
2003 Runx3 is required for CD8+ T cell maturation in the thymus; Runx3-deficient mice show impaired CD8 T cell lineage decisions with aberrant CD4 expression on peripheral CD8 T cells and reduced cytotoxic activity. Genetic epistasis with Runx1 (Runx3-/-;Runx1+/-) results in complete absence of single-positive CD8+ T cells, indicating both act as transcriptional repressors of CD4 during T cell lineage decisions. Runx3 knockout mice, compound Runx3/Runx1 mutants, flow cytometry, in vitro cytotoxicity assay Proceedings of the National Academy of Sciences of the United States of America High 12796513
2010 Src kinase phosphorylates RUNX3 at tyrosine residues, causing cytoplasmic mislocalization; Src knockdown or kinase inhibition causes re-localization of RUNX3 to the nucleus, identifying Src-mediated tyrosine phosphorylation as a mechanism of RUNX3 inactivation in gastric and breast cancer. Overexpression of Src, co-immunoprecipitation, siRNA knockdown of Src, chemical kinase inhibition, subcellular fractionation/immunofluorescence The Journal of biological chemistry High 20100835
2017 Runx3 programs CD8+ T cell tissue residency (TRM cells) by supporting expression of tissue-residency genes and suppressing genes associated with tissue egress; Runx3-deficient CD8+ TILs fail to accumulate in tumors, while Runx3 overexpression enhances tumor-specific CD8+ T cell abundance and delays tumor growth. Pooled in vivo RNAi screen, Runx3 conditional knockout, adoptive T cell transfer, gene expression profiling, chromatin accessibility (ATAC-seq) Nature High 29211713
2017 Runx3 plays a critical role at the restriction (R)-point in the G1-S transition; Runx3 transiently forms a complex with pRb and Brd2 to induce p21 (Cdkn1a) expression. Cyclin D-CDK4/6 promotes dissociation of this complex, turning off p21. Runx3-/- MEFs show dysregulated R-point and tumor formation in nude mice. Runx3 knockout MEFs, co-immunoprecipitation, luciferase reporter, nude mouse tumorigenicity, reconstitution experiments with oncogenic K-Ras Oncogene High 28846108
2012 RUNX3 is a component of the MST/Hippo signaling pathway; SAV1/WW45 facilitates close association between MST2 and RUNX3, and MST2 stimulates SAV1-RUNX3 interaction. RUNX3 knockdown abolishes MST/Hpo-mediated cell death, identifying RUNX3 as an endpoint effector of this pathway. Co-immunoprecipitation, siRNA knockdown, cell death assays Journal of cellular physiology Medium 21678419
2020 Under hypoxia, G9a (KMT) methylates RUNX3 at K129 and K171 via interaction with the Runt domain; this methylation inactivates RUNX3 transactivation by reducing interactions with CBFβ and p300 cofactors and reducing p300-mediated acetylation of RUNX3, which is involved in nuclear import via importin-α1. Co-immunoprecipitation, in vitro methylation assay, site-directed mutagenesis, immunofluorescence localization, cell proliferation assays Cell death and differentiation High 33116296
2019 RUNX3 directly interacts with GLI1 and promotes its ubiquitination (via E3 ligase β-TrCP), thereby inhibiting Hedgehog signaling to suppress stemness and metastasis in colorectal cancer. Co-immunoprecipitation, ubiquitination assay, knockdown/overexpression experiments, correlation analysis in CRC tissues Cell death and differentiation Medium 31278361
2019 RUNX3 induces apoptosis in colorectal cancer cells via TRAIL by inhibiting SOD3 transcription (binding to SOD3 promoter), thereby increasing ROS and ER stress, which upregulates CHOP and DR5. Chromatin immunoprecipitation (ChIP), luciferase reporter, overexpression/knockdown, ROS measurement, flow cytometry, xenograft model Oncogene Medium 30692634
2007 Runx3 directly binds to the Osterix promoter at a specific RUNX-responsive element (AGTGGTT, -713 to -707 bp) and negatively regulates Osterix expression in dental pulp cells, as demonstrated by EMSA and ChIP assays; mutation of this site abolishes repression. Luciferase reporter assay, electrophoretic mobility shift assay (EMSA), chromatin immunoprecipitation (ChIP), site-directed mutagenesis The Biochemical journal High 17352693
2007 Runx3 regulates both early and late stages of chondrocyte differentiation; Runx3 gain-of-function and loss-of-function alter markers of chondrocyte maturation, and Runx3 transcriptionally inhibits Runx1 expression in chondrocytes. siRNA knockdown, overexpression, luciferase reporter assay, real-time RT-PCR, immunohistochemistry in mouse embryos Journal of bone and mineral research Medium 17488194
2006 RUNX3 negatively regulates CD36 expression in myeloid cells by directly binding two functional RUNX-binding elements in the CD36 gene proximal regulatory region in vitro and in vivo; RUNX3 overexpression in myeloid cells drastically diminishes CD36 expression. Luciferase reporter assay, EMSA, chromatin immunoprecipitation (ChIP), overexpression in myeloid cells Journal of immunology Medium 16887969
2006 Runx3 is required for development of skin dendritic epidermal T cells (DETCs) by regulating expression of the αEβ7 integrin CD103 and IL-2Rβ, affecting proliferation and epithelial retention of DETC precursors. Runx3 knockout mice, flow cytometry, gene expression analysis Developmental biology Medium 17222403
2014 Runx3 cooperates with ETS and T-box transcription factors to drive the IL-15-mediated transcription program during natural killer cell activation; loss of Runx3 impairs IL-15-dependent accumulation of mature NK cells in vivo and uterine NK cells are completely absent in pregnant Runx3-/- mice. Runx3 knockout mice, ChIP-seq, RNA-seq/differential gene expression analysis, in vivo NK cell quantification Molecular and cellular biology High 24421391
2013 Runx3 regulates a transcriptional program in CD8+ T and NK cells; Runx3-bound genomic regions are enriched for RUNX and ETS motifs and overlap with T-bet/p300-bound enhancer regions; IL-2 activation expands the set of Runx3-regulated genes to include proliferation, cytotoxicity, migration and cytokine production genes. ChIP-seq, transcriptome analysis of wild-type vs. Runx3-/- primary cells PloS one High 24236182
2008 RUNX3 transcription is repressed by the AML fusion proteins RUNX1-ETO (t(8;21)) and CBFβ-MYH11 (inv(16)) acting directly or indirectly through two conserved RUNX binding sites in the RUNX3 P1 promoter, not by P2 methylation; ectopic expression of fusion proteins also inhibits endogenous RUNX3 expression in vitro. Luciferase reporter assay, promoter analysis, ectopic expression in cell lines, methylation analysis Blood Medium 18663147
2009 RUNX3 represses RUNX1 expression in proliferating human B cells; this repression of RUNX1 by RUNX3 is required to allow cell proliferation at a key B-cell developmental stage. Expression analysis in B cell lines, functional studies of RUNX1/RUNX3 interplay Journal of cellular physiology Low 19603429
2007 Runx3 physically interacts with DNA repair protein Ku70 (and Ku80) in vivo and in vitro; the interaction requires amino acids 241-322 of Runx3 (transcriptional activation domain) and amino acids 1-116 of Ku70; Ku70 knockdown enhances Runx3-mediated p21 transcriptional activation. Affinity purification/mass spectrometry, His-tag pull-down, co-immunoprecipitation, immunofluorescence, siRNA knockdown Experimental cell research Medium 17662272
2012 RUNX3 negatively regulates ICAM-3 expression during macrophage differentiation; RUNX3 occupies RUNX cognate sequences in the ICAM-3 promoter in vivo, and siRNA-mediated reduction of RUNX3 increases ICAM-3 mRNA levels; RUNX3 cooperates with Ets and C/EBP family factors at the ICAM-3 promoter. Luciferase reporter assay, ChIP, siRNA knockdown, protein expression analysis PloS one Medium 22479382
2017 RUNX3 directly binds the promoter of miR-182 (by ChIP) and regulates its expression; miR-182 targets HOXA9 (validated by luciferase assay), establishing a RUNX3→miR-182→HOXA9 axis that inhibits gastric cancer cell proliferation, migration, and invasion. ChIP assay, luciferase reporter assay, qRT-PCR, Western blot, EdU proliferation, Transwell assay, xenograft mouse model Biomedicine & pharmacotherapy Medium 29054094
2017 RUNX3 loss leads to transcriptional downregulation of the redox regulator HO-1 (HMOX1), which elevates oxidative DNA damage and causes DNA double-strand breaks, triggering cellular senescence and acquisition of the senescence-associated secretory phenotype (SASP) under TGFβ stimulation. RUNX3 loss-of-function in cancer cells, gene expression analysis, DNA damage assays, ROS measurement, co-relation with TGFβ gene signature in tumor datasets Cancer research Medium 29074538
2015 Runx3 is expressed in osteoblast precursors and Runx3-deficient osteoblast-specific (Col1α1-cre) mice develop severe congenital osteopenia due to decreased osteoblast numbers from diminished proliferation; Runx3-null osteoblast transcriptomes show decreased osteoblastic markers and increased Notch signaling components. Conditional knockout mice (osteoblast-specific Cre), bone histomorphometry, primary osteoblast culture, transcriptome analysis Molecular and cellular biology High 25605327
2017 MYC directly binds the RUNX3 enhancer region (shown by ChIP-qPCR) and positively regulates RUNX3 transcription in NK/T-cell lymphoma (NKTL); co-transfection of MYC with RUNX3 enhancer reporter activates transcription; MYC inhibition (JQ1) causes downregulation of both MYC and RUNX3. ChIP-qPCR, luciferase reporter assay, JQ1 treatment, ectopic MYC expression rescue experiment Leukemia Medium 28119527
2020 RUNX3 overexpression in Tet2-deficient hematopoietic stem/progenitor cells suppresses Runx1 expression and its target genes (Cebpa, Csf1r) by binding Runx1-regulatory regions and remodeling chromatin, while activating Myc target genes; this drives MDS-like transformation in vivo. RUNX3-overexpressing Tet2-deficient mouse model, ChIP-seq, RNA-seq, in vivo hematopoiesis analysis Cancer research High 32341038
2021 Runx1 and Runx3 are co-expressed in single pro-T cells, bind highly overlapping genomic sites, and have redundant/collaborative functions in T-lineage gene activation and progenitor gene repression during T cell commitment; they shift binding sites extensively during commitment, with functionally distinct sites characterized by different co-factor binding patterns. Single and double Runx CRISPR/Cas9 knockouts, ChIP-seq, RNA-seq, stage-specific analysis Proceedings of the National Academy of Sciences of the United States of America High 33479171
1999 AML2/RUNX3 protein in hematopoietic cells is a nuclear serine phosphoprotein associated with the nuclear matrix; its expression is induced by all-trans retinoic acid, 13-cis-RA, and 9-cis-RA through the RARα-specific signaling pathway (not RXR), as demonstrated using selective agonists/antagonists. Western blot, nuclear fractionation, pharmacological induction with retinoid receptor-selective ligands and antagonists The Journal of biological chemistry Medium 10419474
2015 Nr4a1 directly suppresses Runx3 expression in CD8+ T cells by recruiting the corepressor CoREST to the Runx3 locus; loss of Nr4a1 results in increased Runx3 expression in thymocytes and a 2-fold increase in CD8+ T cell frequency. Nr4a1 knockout mice, ChIP (Nr4a1 binding to Runx3 promoter with CoREST), flow cytometry Scientific reports Medium 25762306
2014 RUNX3 inhibits survivin expression by directly binding to a RUNX3-binding site in the survivin gene promoter; RUNX3-R122C mutation (Runt domain) abolishes binding and has no effect on survivin promoter activity, demonstrating DNA-binding dependence. Luciferase reporter assay, ChIP, overexpression/knockdown, site-directed mutagenesis (R122C), apoptosis assays European journal of cell biology Medium 24636883
2013 Runx3 binds the TSP-1 (thrombospondin-1) promoter and stimulates its transcriptional activity and protein expression in melanoma cells; Runx3 expression dramatically increases TSP-1 at both transcriptional and translational levels. Promoter luciferase reporter assay, ChIP, qRT-PCR, Western blot, overexpression International journal of molecular sciences Medium 23846726
2023 RUNX3 deficiency in liver sinusoidal endothelial cells (LSECs) leads to IL-6/JAK/STAT3 pathway activation and LSEC dysfunction; RUNX3-deficient LSECs secrete LRG1, which activates hepatic stellate cells via TGFBR1-SMAD2/3 signaling in a paracrine manner, driving liver fibrosis. Endothelial-specific Runx3 knockout mice, single-cell RNA-seq, co-culture experiments, mechanistic pathway analysis (IL-6/JAK/STAT3, TGFBR1-SMAD2/3) Hepatology Medium 39042837
2022 Runx3 directly regulates lubricin and aggrecan as transcriptional target genes in articular chondrocytes; Runx3-knockout mice show accelerated osteoarthritis after surgical induction with decreased lubricin and aggrecan; intra-articular Runx3 adenovirus ameliorates osteoarthritis. Runx3 conditional knockout mice, comprehensive transcriptional analyses, adenovirus rescue, surgical osteoarthritis model Nature communications High 36261443
2023 RUNX3 induces ferroptosis in gallbladder cancer cells by activating ING1 transcription (validated by dual-luciferase reporter and ChIP assay), thereby repressing SLC7A11 in a p53-dependent manner; RUNX3 promoter methylation by DNMT1 suppresses this ferroptosis pathway. Dual-luciferase reporter assay, ChIP, gain/loss-of-function assays in vitro and in vivo, bisulfite sequencing PCR Cellular signalling Medium 37156453
2019 Runx3 is required for maintenance of cell identity of a muscle-selective subgroup of proprioceptive sensory neurons (PSNs) and controls sensorimotor connections between PSNs and motor neurons; muscle-derived neurotrophin 3 (NT3) signaling is necessary for maintenance of RUNX3 expression in PSNs. Conditional Runx3 inactivation in PSNs after peripheral innervation, anatomical tracing, electrophysiology, genetic ablation Development (Cambridge, England) Medium 31575648
2023 Runx3-expressing vagal sensory neurons (subsets also expressing Prox2) form intraganglionic laminar endings in the esophagus and stomach; genetic ablation of Prox2 and Runx3 neurons demonstrates their essential role in esophageal peristalsis in freely behaving mice. Genetically guided anatomical tracing, optogenetics, electrophysiology, genetic ablation Neuron Medium 37192624
2019 NO•-induced IDO1/Kynurenine/AHR signaling in pancreatic cancer is mediated by RUNX3 transcription factor, establishing a NO•/RUNX3/Kynurenine metabolic axis that enhances disease aggressiveness. Gene expression correlation analysis, NO• donor treatment, IDO1/kynurenine measurements, mechanistic pathway analysis in pancreatic cancer cell lines International journal of cancer Low 31609478
2019 RUNX1 and RUNX3 physically interact with YAP and act as negative regulators of YAP oncogenic function in mammary epithelial cells; RUNX1/RUNX3 inhibit YAP-mediated migration and stemness in an interaction-dependent manner and co-regulate YAP-mediated gene expression. Co-immunoprecipitation, overexpression/knockdown, migration assay, mammosphere formation Oncotarget Medium 29581836
2014 RUNX3 binds to EWS/FLI via its Runt domain in Ewing sarcoma cells; EWS/FLI prevents RUNX3 from activating a RUNX-responsive reporter (p6OSE2); stable suppression of RUNX3 delays anchorage-independent colony growth and reverses EWS/FLI-responsive gene expression. Co-immunoprecipitation, luciferase reporter assay, stable shRNA knockdown, soft agar colony assay Journal of cellular physiology Medium 24812032

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 Causal relationship between the loss of RUNX3 expression and gastric cancer. Cell 897 11955451
2017 Runx3 programs CD8+ T cell residency in non-lymphoid tissues and tumours. Nature 569 29211713
1994 AML1, AML2, and AML3, the human members of the runt domain gene-family: cDNA structure, expression, and chromosomal localization. Genomics 366 7835892
2003 Runx3 and Runx1 are required for CD8 T cell development during thymopoiesis. Proceedings of the National Academy of Sciences of the United States of America 321 12796513
2010 The chemokine CXCL12 regulates monocyte-macrophage differentiation and RUNX3 expression. Blood 260 20930067
2001 The RUNX3 gene--sequence, structure and regulated expression. Gene 161 11733147
2001 Spatial and temporal expression pattern of Runx3 (Aml2) and Runx1 (Aml1) indicates non-redundant functions during mouse embryogenesis. Mechanisms of development 160 11731260
2005 RUNX3 inactivation by point mutations and aberrant DNA methylation in bladder tumors. Cancer research 132 16230397
2004 Tumor suppressor activity of RUNX3. Oncogene 111 15156190
2009 Molecular pathology of RUNX3 in human carcinogenesis. Biochimica et biophysica acta 101 19682550
2013 Overexpressed miR-301a promotes cell proliferation and invasion by targeting RUNX3 in gastric cancer. Journal of gastroenterology 80 23338485
2014 Transcription factor Runx3 regulates interleukin-15-dependent natural killer cell activation. Molecular and cellular biology 79 24421391
2009 RUNX3 has an oncogenic role in head and neck cancer. PloS one 71 19521519
2006 RUNX3 protein is overexpressed in human basal cell carcinomas. Oncogene 68 16767156
2005 Decreased expression and frequent allelic inactivation of the RUNX3 gene at 1p36 in human hepatocellular carcinoma. Liver international : official journal of the International Association for the Study of the Liver 68 15780064
2018 RUNX1 and RUNX3 protect against YAP-mediated EMT, stem-ness and shorter survival outcomes in breast cancer. Oncotarget 67 29581836
2015 The emerging role of RUNX3 in cancer metastasis (Review). Oncology reports 67 26708741
2022 Runx2 and Runx3 differentially regulate articular chondrocytes during surgically induced osteoarthritis development. Nature communications 64 36261443
2015 Runx3 at the interface of immunity, inflammation and cancer. Biochimica et biophysica acta 64 25641675
2019 RUNX3 suppresses metastasis and stemness by inhibiting Hedgehog signaling in colorectal cancer. Cell death and differentiation 62 31278361
2017 RUNX3 is oncogenic in natural killer/T-cell lymphoma and is transcriptionally regulated by MYC. Leukemia 59 28119527
2013 Runx3-mediated transcriptional program in cytotoxic lymphocytes. PloS one 58 24236182
2007 Runx3/AML2/Cbfa3 regulates early and late chondrocyte differentiation. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 56 17488194
2009 The expression of RUNX3 in colorectal cancer is associated with disease stage and patient outcome. British journal of cancer 55 19223906
2003 Runx3 knockouts and stomach cancer. EMBO reports 50 12776174
1999 Regulation of AML2/CBFA3 in hematopoietic cells through the retinoic acid receptor alpha-dependent signaling pathway. The Journal of biological chemistry 50 10419474
2006 Runx3 regulates dendritic epidermal T cell development. Developmental biology 49 17222403
2002 The common retroviral insertion locus Dsi1 maps 30 kilobases upstream of the P1 promoter of the murine Runx3/Cbfa3/Aml2 gene. Journal of virology 49 11932403
2023 Epigenetic reprogramming of Runx3 reinforces CD8 + T-cell function and improves the clinical response to immunotherapy. Molecular cancer 48 37189103
2013 RUNX3 suppresses migration, invasion and angiogenesis of human renal cell carcinoma. PloS one 48 23457532
2004 Growth regulation of gastric epithelial cells by Runx3. Oncogene 47 15156189
1995 Identification of a new murine runt domain-containing gene, Cbfa3, and localization of the human homolog, CBFA3, to chromosome 1p35-pter. Genomics 47 7607690
2019 miR-301a promotes lung tumorigenesis by suppressing Runx3. Molecular cancer 46 31122259
2015 Loss of osteoblast Runx3 produces severe congenital osteopenia. Molecular and cellular biology 46 25605327
2007 Promoter hypermethylation of the RUNX3 gene in esophageal squamous cell carcinoma. Cancer investigation 45 18058463
2021 Runx1 and Runx3 drive progenitor to T-lineage transcriptome conversion in mouse T cell commitment via dynamic genomic site switching. Proceedings of the National Academy of Sciences of the United States of America 44 33479171
2011 Oncogenic role of RUNX3 in head and neck cancer. Journal of cellular biochemistry 44 21268058
2010 Src kinase phosphorylates RUNX3 at tyrosine residues and localizes the protein in the cytoplasm. The Journal of biological chemistry 44 20100835
2008 Transcriptional repression of the RUNX3/AML2 gene by the t(8;21) and inv(16) fusion proteins in acute myeloid leukemia. Blood 43 18663147
2004 RUNX3 expression in primary and metastatic pancreatic cancer. Journal of clinical pathology 42 14990603
2011 Association between RUNX3 promoter methylation and gastric cancer: a meta-analysis. BMC gastroenterology 40 21867527
2019 NO• /RUNX3/kynurenine metabolic signaling enhances disease aggressiveness in pancreatic cancer. International journal of cancer 39 31609478
2018 Emerging role of RUNX3 in the regulation of tumor microenvironment. BMB reports 39 29429451
2023 Prox2 and Runx3 vagal sensory neurons regulate esophageal motility. Neuron 38 37192624
2014 Role of RUNX3 in suppressing metastasis and angiogenesis of human prostate cancer. PloS one 38 24475196
2003 Runx3 is required for hematopoietic development in zebrafish. Developmental dynamics : an official publication of the American Association of Anatomists 38 14579373
2004 Expression of RUNX3 protein in human gastric mucosa, intestinal metaplasia and carcinoma. European journal of clinical investigation 36 15379759
2018 RUNX3 inhibits glioma survival and invasion via suppression of the β-catenin/TCF-4 signaling pathway. Journal of neuro-oncology 34 29916101
2019 RUNX3 enhances TRAIL-induced apoptosis by upregulating DR5 in colorectal cancer. Oncogene 33 30692634
2015 The nuclear receptor nr4a1 controls CD8 T cell development through transcriptional suppression of runx3. Scientific reports 33 25762306
2015 TrkB Promotes Breast Cancer Metastasis via Suppression of Runx3 and Keap1 Expression. Molecules and cells 33 26657794
2017 Runx3 in Immunity, Inflammation and Cancer. Advances in experimental medicine and biology 32 28299669
2017 RUNX3 inhibits the proliferation and metastasis of gastric cancer through regulating miR-182/HOXA9. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 32 29054094
2020 RUNX3 methylation drives hypoxia-induced cell proliferation and antiapoptosis in early tumorigenesis. Cell death and differentiation 31 33116296
2012 RUNX3 regulates intercellular adhesion molecule 3 (ICAM-3) expression during macrophage differentiation and monocyte extravasation. PloS one 31 22479382
2010 RUNX3 methylation and expression associated with advanced precancerous gastric lesions in a Chinese population. Carcinogenesis 31 21135153
2015 RUNX3 contributes to carboplatin resistance in epithelial ovarian cancer cells. Gynecologic oncology 30 26186909
2020 Oncogenic RUNX3: A Link between p53 Deficiency and MYC Dysregulation. Molecules and cells 28 31991537
2019 Genetic variants in RUNX3, AMD1 and MSRA in the methionine metabolic pathway and survival in nonsmall cell lung cancer patients. International journal of cancer 27 30650190
2019 RUNX3 and T-Bet in Immunopathogenesis of Ankylosing Spondylitis-Novel Targets for Therapy? Frontiers in immunology 27 30687330
2017 RUNX3 regulates hepatocellular carcinoma cell metastasis via targeting miR-186/E-cadherin/EMT pathway. Oncotarget 27 28977878
2019 Dysregulation of the TOX-RUNX3 pathway in cutaneous T-cell lymphoma. Oncotarget 26 31139323
2018 RUNX3-Mediated Immune Cell Development and Maturation. Critical reviews in immunology 26 29717663
2017 Barcoded NS31/AML2 primers for sequencing of arbuscular mycorrhizal communities in environmental samples. Applications in plant sciences 26 28924511
2017 TGFβ Promotes Genomic Instability after Loss of RUNX3. Cancer research 24 29074538
2016 RUNX3 inhibits the metastasis and angiogenesis of colorectal cancer. Oncology reports 24 27633042
2011 Control of RUNX3 by histone methyltransferases. Journal of cellular biochemistry 24 21268059
2023 RUNX3 in Stem Cell and Cancer Biology. Cells 23 36766749
2023 DNA methylation of RUNX3 promotes the progression of gallbladder cancer through repressing SLC7A11-mediated ferroptosis. Cellular signalling 23 37156453
2018 DNA methylation affects metastasis of renal cancer and is associated with TGF-β/RUNX3 inhibition. Cancer cell international 22 29651226
2017 Runx3 plays a critical role in restriction-point and defense against cellular transformation. Oncogene 22 28846108
2020 Elevated expression of RUNX3 co-expressing with EZH2 in esophageal cancer patients from India. Cancer cell international 20 32943993
2019 Renal cell carcinoma: predicting RUNX3 methylation level and its consequences on survival with CT features. European radiology 20 30877466
2011 Expression of RUNX3 in skin cancers. Clinical and experimental dermatology 20 21623876
2009 RUNX3 gene methylation in epithelial ovarian cancer tissues and ovarian cancer cell lines. Omics : a journal of integrative biology 20 19645591
2007 Runx3 negatively regulates Osterix expression in dental pulp cells. The Biochemical journal 20 17352693
2024 Endothelial RUNX3 controls LSEC dysfunction and angiocrine LRG1 signaling to prevent liver fibrosis. Hepatology (Baltimore, Md.) 19 39042837
2019 Muscle-selective RUNX3 dependence of sensorimotor circuit development. Development (Cambridge, England) 19 31575648
2014 RUNX3 facilitates growth of Ewing sarcoma cells. Journal of cellular physiology 19 24812032
2014 Association of promoter methylation of RUNX3 gene with the development of esophageal cancer: a meta analysis. PloS one 19 25229459
2013 Thrombospondin-1 is a putative target gene of Runx2 and Runx3. International journal of molecular sciences 19 23846726
2012 Identification of RUNX3 as a component of the MST/Hpo signaling pathway. Journal of cellular physiology 19 21678419
2006 RUNX3 negatively regulates CD36 expression in myeloid cell lines. Journal of immunology (Baltimore, Md. : 1950) 19 16887969
2019 RUNX3 levels in human hematopoietic progenitors are regulated by aging and dictate erythroid-myeloid balance. Haematologica 18 31171641
2017 EZH2 promotes cell proliferation by regulating the expression of RUNX3 in laryngeal carcinoma. Molecular and cellular biochemistry 18 28795320
2016 RUNX3 is down-regulated in glioma by Myc-regulated miR-4295. Journal of cellular and molecular medicine 18 26756701
2009 RUNX3-mediated repression of RUNX1 in B cells. Journal of cellular physiology 18 19603429
2018 Runx3 regulates folliculogenesis and steroidogenesis in granulosa cells of immature mice. Cell and tissue research 17 30377784
2017 Loss of RUNX3 expression inhibits bone invasion of oral squamous cell carcinoma. Oncotarget 16 28030842
2017 HSD11B2, RUNX3, and LINE-1 Methylation in Placental DNA of Hypertensive Disorders of Pregnancy Patients. Reproductive sciences (Thousand Oaks, Calif.) 16 29017438
2010 Pathobiologic implications of methylation and expression status of Runx3 and CHFR genes in gastric cancer. Medical oncology (Northwood, London, England) 16 20300977
2023 RUNX3 Meets the Ubiquitin-Proteasome System in Cancer. Cells 15 36899853
2020 Overexpression of RUNX3 Represses RUNX1 to Drive Transformation of Myelodysplastic Syndrome. Cancer research 15 32341038
2018 The correlation between Runx3 and bronchial asthma. Clinica chimica acta; international journal of clinical chemistry 15 30218658
2007 Runx3 interacts with DNA repair protein Ku70. Experimental cell research 15 17662272
2005 Expression of RUNX3 protein in human esophageal mucosa and squamous cell carcinoma. Pathobiology : journal of immunopathology, molecular and cellular biology 15 16582583
2022 Increased expression of RUNX3 inhibits normal human myeloid development. Leukemia 14 35490198
2017 RUNX3 and p53: How Two Tumor Suppressors Cooperate Against Oncogenic Ras? Advances in experimental medicine and biology 14 28299666
2014 RUNX3 inhibits survivin expression and induces cell apoptosis in gastric cancer. European journal of cell biology 14 24636883
2014 Clinicopathological significance of RUNX3 gene hypermethylation in hepatocellular carcinoma. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 14 25037468

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