Affinage

RUNX3

Runt-related transcription factor 3 · UniProt Q13761

Length
415 aa
Mass
44.4 kDa
Annotated
2026-04-28
100 papers in source corpus 41 papers cited in narrative 41 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

RUNX3 is a Runt-domain transcription factor that functions as a context-dependent regulator of cell proliferation, apoptosis, and lineage specification across epithelial, immune, skeletal, and neuronal tissues. It acts downstream of TGF-β and BMP signaling to mediate growth inhibition and apoptosis in gastric and colorectal epithelial cells—where it directly represses c-Myc and activates p21—and cooperates with p53 in the DNA damage response by promoting p53 Ser-15 phosphorylation and forming a transient pRb–Brd2 complex at the restriction point (PMID:11955451, PMID:20353948, PMID:28846108, PMID:20442291). In the immune system, RUNX3 is essential for CD8+ T cell maturation, tissue-resident memory T cell differentiation, NK cell activation, and iTreg function through direct transcriptional control of CD4 silencing, FOXP3, and IL-15-dependent gene programs (PMID:12796513, PMID:29211713, PMID:19917773, PMID:24421391). RUNX3 is post-translationally regulated by CDK4-mediated phosphorylation at Ser356 triggering proteasomal degradation, MDM2-mediated ubiquitination promoting nuclear export, and G9a-mediated methylation at K129/K171 impairing CBFβ/p300 interactions and nuclear import; cytoplasmic mislocalization constitutes a major inactivation mechanism in cancer (PMID:19351720, PMID:19808967, PMID:33116296, PMID:16818622).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 1998 High

    Establishing that RUNX3 is a TGF-β-inducible transcription factor that directly binds DNA to activate gene expression resolved its initial molecular identity as a signal-responsive transcriptional activator.

    Evidence TGF-β1 treatment of B cells with EMSA and luciferase reporter assays on the germline Igα promoter

    PMID:9862705

    Open questions at the time
    • No genome-wide binding data at this stage
    • Mechanism of TGF-β-mediated RUNX3 induction not defined
  2. 2002 High

    Demonstrating that Runx3 loss causes gastric epithelial hyperplasia through loss of TGF-β-mediated growth inhibition and apoptosis established RUNX3 as a bona fide tumor suppressor and linked its Runt domain to this function.

    Evidence Runx3 knockout mouse with gastric hyperplasia; TGF-β resistance in primary cells; R122C Runt domain mutation abolishing suppression; tumorigenicity assays

    PMID:11955451

    Open questions at the time
    • Direct transcriptional targets mediating tumor suppression not identified
    • Whether tumor-suppressive function extends beyond gastric epithelium unknown
  3. 2003 High

    Showing that Runx3 represses CD4 and is required for CD8+ T cell maturation—with Runx1 acting redundantly—revealed RUNX3's central role in T cell lineage decisions.

    Evidence Runx3 KO and compound Runx3/Runx1 mutant mice with flow cytometry of thymic subsets

    PMID:12796513

    Open questions at the time
    • Direct CD4 silencer binding by Runx3 not shown at this stage
    • Downstream gene program not characterized genome-wide
  4. 2004 High

    The discovery that Runx2/Runx3 double knockout abolishes chondrocyte maturation and Ihh expression established functional redundancy among Runx family members in skeletal development and identified Ihh as a direct transcriptional target.

    Evidence Runx2/Runx3 double-KO mice; ChIP and reporter assays on the Ihh promoter

    PMID:15107406

    Open questions at the time
    • Relative contributions of Runx2 vs Runx3 to individual target genes not delineated
    • Post-translational regulation in chondrocytes unexplored
  5. 2006 Medium

    Identifying cytoplasmic mislocalization of RUNX3 in breast cancer as a distinct inactivation mechanism, and showing that nuclear RUNX3 directly regulates CD36 and ICAM-3 in myeloid cells, broadened understanding of both its tumor suppressor inactivation and immune-cell transcriptional programs.

    Evidence IHC/subcellular fractionation in breast tumors with invasion/tumorigenicity assays; EMSA and ChIP at CD36 and ICAM-3 promoters with overexpression/knockdown

    PMID:16818622 PMID:16887969 PMID:17222403

    Open questions at the time
    • Mechanism driving cytoplasmic mislocalization not identified
    • No ChIP confirmation for integrin targets CD11a/CD49d
  6. 2007 Medium

    Mapping Runx3 interaction with Ku70 and demonstrating direct repression of the Osterix promoter expanded the catalog of RUNX3 partners and transcriptional targets in skeletal and DNA repair contexts.

    Evidence Affinity purification/mass spectrometry identifying Ku70; in vitro pulldown and Co-IP mapping domains; ChIP and EMSA at the Osterix promoter; Runx3 gain/loss of function in chondrocytes

    PMID:17352693 PMID:17488194 PMID:17662272

    Open questions at the time
    • Functional significance of Ku70 interaction in DNA repair not tested in vivo
    • Whether Osterix repression is physiologically relevant in osteoblasts vs dental cells unclear
  7. 2009 High

    Elucidating two post-translational degradation pathways—CDK4 phosphorylation at Ser356 and MDM2-mediated ubiquitination—revealed how RUNX3 protein levels are dynamically controlled in proliferating and oncogene-activated cells, and RUNX3's direct binding to the FOXP3 promoter established its role in iTreg differentiation.

    Evidence In vitro CDK4 kinase assay with S356A mutagenesis and Ccnd1-KO mice; Co-IP/ubiquitination assays for MDM2-RUNX3; ChIP at FOXP3 promoter with Cbfb conditional KO and Treg suppression assays

    PMID:19351720 PMID:19808967 PMID:19917773

    Open questions at the time
    • Identity of the E3 ligase for CDK4-dependent ubiquitylation unknown
    • Whether MDM2-mediated export occurs in non-cancer contexts untested
    • Relative importance of RUNX3 vs RUNX1 at the FOXP3 promoter unclear
  8. 2010 High

    Demonstrating that RUNX3 cooperates with p53 in the DNA damage response and suppresses c-Myc downstream of BMP signaling established RUNX3 as an integrator of multiple tumor-suppressive signaling pathways.

    Evidence Co-IP and GST pulldown of RUNX3-p53; p53 transcriptional reporters and ATM interaction; BMP treatment with c-Myc and TCF reporter assays in colorectal cancer cells

    PMID:20353948 PMID:20442291

    Open questions at the time
    • Structural basis of p53–RUNX3 interaction unknown
    • Direct BMP-responsive element in RUNX3 gene not mapped
  9. 2012 Medium

    Placing RUNX3 downstream of the MST/Hippo pathway as an effector mediating MST-induced apoptosis linked RUNX3 to a fourth major growth-control signaling axis.

    Evidence Co-immunoprecipitation of RUNX3 with MST2 and SAV1; siRNA knockdown ablating MST-mediated cell death

    PMID:21678419

    Open questions at the time
    • No direct phosphorylation or other post-translational modification by MST on RUNX3 demonstrated
    • Single lab; not independently replicated
  10. 2015 High

    Conditional knockout studies established a cell-autonomous role for Runx3 in osteoblast proliferation and bone mass maintenance, distinct from its chondrocyte functions.

    Evidence Osteoblast-specific (Col1α1-Cre) vs chondrocyte-specific (Col1α2-Cre) Runx3 KO mice with bone histomorphometry and primary osteoblast culture

    PMID:25605327

    Open questions at the time
    • Direct osteoblast target genes not identified by ChIP
    • Relationship to Runx2 in this lineage not fully resolved
  11. 2017 High

    Multiple 2017 studies consolidated RUNX3's role at the restriction point via a pRb–Brd2 complex, in tissue-resident memory CD8+ T cell differentiation, and as an MYC-driven oncogene in NK/T-cell lymphoma, revealing its fundamentally context-dependent function.

    Evidence Co-IP of pRb-Runx3-Brd2 with cyclin D dissociation and Runx3-null MEF tumorigenesis; in vivo RNAi screen and conditional KO for TRM cells; ChIP-qPCR of MYC at RUNX3 enhancer in NKTL

    PMID:28119527 PMID:28846108 PMID:29211713

    Open questions at the time
    • Structural determinants of pRb–Brd2–RUNX3 complex formation unknown
    • Whether RUNX3 overexpression in NKTL bypasses normal post-translational controls not tested
    • Chromatin remodeling targets in TRM program not fully delineated
  12. 2020 High

    Identifying G9a-mediated methylation at K129/K171 as a mechanism that inactivates RUNX3 by disrupting CBFβ/p300 interactions and nuclear import revealed a hypoxia-responsive epigenetic layer of RUNX3 regulation, while RUNX3 overexpression in Tet2-deficient MDS showed it can suppress RUNX1 targets and activate MYC programs.

    Evidence In vitro methylation assay with mass spectrometry; interaction assays with CBFβ, p300, importin-α1; ChIP-seq of RUNX3 in Tet2-deficient mouse MDS model

    PMID:32341038 PMID:33116296

    Open questions at the time
    • Whether G9a methylation occurs in non-cancer contexts not established
    • Whether demethylases reverse RUNX3 methylation unknown
    • Mechanism of RUNX3 overexpression in human MDS not defined
  13. 2021 High

    Genome-wide ChIP-seq in pro-T cells demonstrated that Runx1 and Runx3 bind highly overlapping sites and have redundant functions in T-lineage commitment, resolving the question of why single knockouts show incomplete phenotypes.

    Evidence CRISPR single and double Runx1/Runx3 KO in pro-T cells with ChIP-seq and transcriptomics

    PMID:33479171

    Open questions at the time
    • How stage-specific binding site shifts are encoded at the chromatin level remains unclear
    • Cofactor requirements for Runx binding specificity at individual loci not resolved
  14. 2022 High

    Demonstrating that Runx3 maintains articular cartilage by driving lubricin and aggrecan expression, and that adenoviral Runx3 delivery ameliorates osteoarthritis, established a protective role distinct from developmental chondrocyte maturation.

    Evidence Runx3-KO mice with surgical OA; transcriptomics identifying lubricin/aggrecan as targets; intra-articular adenoviral Runx3 rescue

    PMID:36261443

    Open questions at the time
    • Direct promoter binding of Runx3 at lubricin and aggrecan loci not confirmed by ChIP
    • Long-term safety and efficacy of adenoviral Runx3 not assessed
  15. 2024 High

    Endothelial-specific Runx3 deletion causing spontaneous liver fibrosis via LRG1-TGFBR1-SMAD2/3 paracrine signaling revealed a previously unrecognized non-epithelial, non-immune role for RUNX3 in vascular homeostasis.

    Evidence Endothelial-specific Runx3 KO mice; scRNA-seq; LSEC-hepatic stellate cell co-culture; LRG1-TGFBR1-SMAD2/3 pathway analysis

    PMID:39042837

    Open questions at the time
    • Whether RUNX3 directly represses LRG1 transcription not shown
    • Relevance to human liver fibrosis beyond LRG1 serum correlation not demonstrated

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include: the structural basis for RUNX3's interaction with its diverse partners (p53, pRb-Brd2, YAP, MDM2); the mechanisms selecting RUNX3 as tumor suppressor versus oncogene in different cellular contexts; and whether pharmacological reactivation of silenced RUNX3 (by demethylation or blocking G9a/MDM2) has therapeutic potential.
  • No crystal structure of RUNX3 with any partner complex available
  • Context-dependent switch between tumor suppressor and oncogene roles mechanistically undefined
  • No therapeutic modulation of RUNX3 activity tested in clinical settings

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 12 GO:0003677 DNA binding 8 GO:0098772 molecular function regulator activity 5
Localization
GO:0005634 nucleus 4 GO:0005829 cytosol 2
Pathway
R-HSA-74160 Gene expression (Transcription) 10 R-HSA-168256 Immune System 6 R-HSA-162582 Signal Transduction 5 R-HSA-1266738 Developmental Biology 3 R-HSA-1643685 Disease 3 R-HSA-5357801 Programmed Cell Death 3 R-HSA-1640170 Cell Cycle 2
Partners
BRD2CBFBEHMT2MDM2RB1TP53XRCC6YAP1
Complex memberships
RUNX3-CBFβpRb-RUNX3-Brd2

Evidence

Reading pass · 41 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2002 RUNX3 is a major growth regulator of gastric epithelial cells acting downstream of TGF-β; Runx3 null mouse gastric mucosa shows hyperplasia due to stimulated proliferation and suppressed apoptosis, and cells are resistant to TGF-β-induced growth inhibition and apoptosis. A Runt domain mutation (R122C) abolished tumor-suppressive activity, establishing the Runt domain as functionally essential. Runx3 knockout mouse model; primary gastric epithelial cell culture with TGF-β treatment; nude mouse tumorigenicity assay with RUNX3 expression variants; site-directed mutagenesis of Runt domain Cell High 11955451
2003 Runx3 functions as a transcriptional repressor of CD4 expression during T cell lineage decisions in the thymus, and is required for CD8+ T cell maturation; compound Runx3-/-;Runx1+/- mice completely lack single-positive CD8+ T cells, indicating that Runx3 and Runx1 cooperate to repress CD4 and drive CD8 lineage commitment. Runx3 knockout mice; compound Runx3/Runx1 mutant mice; flow cytometry of thymic and peripheral T cell subsets; in vitro cytotoxicity assays Proceedings of the National Academy of Sciences of the United States of America High 12796513
2004 Runx2 and Runx3 are both essential for chondrocyte maturation during endochondral ossification; Runx2-/-Runx3-/- double-knockout mice show complete absence of chondrocyte maturation and fail to express Indian hedgehog (Ihh). Runx2 directly binds the Ihh promoter and drives Ihh expression, linking Runx proteins to chondrocyte proliferation and maturation through Ihh induction. Runx2/Runx3 double-knockout mice; adenoviral Runx2 introduction in chondrocyte cultures; luciferase reporter assay with Ihh promoter; chromatin immunoprecipitation (promoter binding) Genes & development High 15107406
1998 RUNX3 (CBFα3/AML2) is induced by TGF-β1 in B cells and binds two CBF binding sites in the TGF-β-responsive element (TβRE) of the germline Ig α promoter to activate IgA class switch transcription. TGF-β1 treatment of splenic B cells and I.29μ B cell line; EMSA demonstrating TGF-β1-inducible complex binding TβRE; overexpression of CBFα family members with luciferase reporter; promoter mutation analysis Journal of immunology High 9862705
2009 PTHrP prevents chondrocyte premature hypertrophy by inducing cyclin D1-dependent CDK4-mediated phosphorylation of Runx3 at Ser356, followed by ubiquitylation and proteasomal degradation. CDK4 directly phosphorylates GST-Runx3 in vitro; S356A mutation stabilizes Runx3 and confers resistance to cyclin D1-induced degradation. Pulse-chase experiments in COS/RCJ3.1C5.18 cells; co-immunoprecipitation of Runx3 with CDK4; in vitro CDK4 kinase assay with GST-Runx3; ubiquitylation assays; proteasome inhibitor rescue; Ccnd1-knockout mouse growth plates; primary chondrocyte PTHrP treatment Journal of cell science High 19351720
2009 RUNX3 is a target of MDM2-mediated ubiquitination; RUNX3 directly binds MDM2 through its Runt domain. MDM2 ubiquitinates RUNX3 on key lysine residues, promoting nuclear export and proteasomal degradation, thereby blocking RUNX3 transcriptional activity. This is stabilized when Ras activates the p14ARF-MDM2 pathway. Co-immunoprecipitation of RUNX3 and MDM2; in vitro ubiquitination assay; domain mapping by deletion mutants; siRNA knockdown; proteasomal degradation assays; Ras activation experiments Cancer research High 19808967
2009 TGF-β induces RUNX1 and RUNX3 expression in CD4+ T cells, which then bind three RUNX binding sites in the FOXP3 promoter to drive Foxp3 expression and inducible regulatory T cell (iTreg) differentiation. CBFβ inactivation in mice and siRNA-mediated RUNX1/RUNX3 knockdown in human T cells reduces Foxp3 expression and iTreg suppressive function. TGF-β treatment of CD4+ T cells; siRNA knockdown of RUNX1/RUNX3; Cbfb conditional KO mice with adoptive transfer; ChIP showing RUNX binding at FOXP3 promoter; in vitro Treg suppression assays; immunofluorescence colocalization The Journal of experimental medicine High 19917773
2010 RUNX3 acts as a co-activator for p53 in DNA damage responses; RUNX3 forms a complex with p53 via the C-terminal portion of p53 (demonstrated by co-IP and GST pulldown), accumulates in the nucleus after DNA damage, promotes phosphorylation of p53 at Ser-15, and interacts with phosphorylated ATM, thereby enhancing p53-dependent transcription and apoptosis. siRNA knockdown of RUNX3; immunoprecipitation of RUNX3-p53 complex; in vitro GST pulldown mapping p53-RUNX3 interaction domains; luciferase reporter assay for p53 transcriptional activity; subcellular fractionation; immunofluorescence colocalization The Journal of biological chemistry High 20353948
2010 RUNX3 functions downstream of BMP signaling in colorectal cancer cells to suppress c-Myc expression via two parallel pathways: direct transcriptional repression of c-Myc and attenuation of β-catenin/TCF transactivation, thereby mediating growth-suppressive effects of BMP. BMP treatment of HT-29 colorectal cancer cells; RUNX3 overexpression and knockdown; luciferase reporter assays for c-Myc promoter and TCF activity; Western blot for c-Myc and β-catenin Cancer research Medium 20442291
2012 RUNX3 is a component of the MST/Hippo signaling pathway; SAV1/WW45 facilitates close association between MST2 and RUNX3, and MST2 stimulates the SAV1-RUNX3 interaction. RUNX3 acts as an endpoint effector of MST, and siRNA knockdown of RUNX3 abolishes MST/Hpo-mediated cell death. Co-immunoprecipitation of RUNX3 with MST2 and SAV1; siRNA knockdown of RUNX3 with MST-induced apoptosis readout Journal of cellular physiology Medium 21678419
2017 Runx3 is a key transcription factor required for tissue-resident memory CD8+ T (TRM) cell differentiation and homeostasis; Runx3 establishes TRM cell populations across diverse tissue environments by supporting tissue-residency genes and suppressing tissue-egress genes. Runx3 overexpression in adoptively transferred CD8+ T cells enhanced tumor-specific T cell accumulation and delayed tumor growth. Pooled in vivo RNAi screen; Runx3 conditional KO mice; chromatin accessibility and gene expression profiling of TRM precursors; adoptive T cell transfer in melanoma mouse model; overexpression of Runx3 in CD8+ T cells Nature High 29211713
2014 Runx3 regulates interleukin-15-dependent natural killer (NK) cell activation; loss of Runx3 impairs IL-15-dependent accumulation of mature NK cells. ChIP-seq combined with differential gene expression showed Runx3 cooperates with ETS and T-box transcription factors to drive the IL-15-mediated transcription program regulating NK cell proliferation, maturation, and migration. Runx3-/- mice; in vivo NK cell quantification; ChIP-seq of Runx3 binding in activated NK cells; differential gene expression analysis of WT vs Runx3-deficient NK cells; uterine NK cell analysis in pregnant Runx3-/- mice Molecular and cellular biology High 24421391
2006 Runx3 regulates development of skin dendritic epidermal T cells (DETCs) by controlling expression of CD103 (αEβ7 integrin) and IL-2Rβ; absence of Runx3 reduces CD103 and IL-2Rβ on DETC precursors, impairing proliferation and maturation, leading to complete loss of skin DETCs. Runx3-/- mice; flow cytometry and histology of skin DETCs; gene expression analysis of CD103 and IL-2Rβ Developmental biology Medium 17222403
2015 Nr4a1 (nuclear receptor) directly suppresses Runx3 expression in CD8+ T cells by recruiting the corepressor CoREST to the Runx3 locus; loss of Nr4a1 increases Runx3 expression in thymocytes, resulting in a 2-fold increase in CD8+ T cell frequency. Nr4a1 knockout mice; ChIP showing Nr4a1 and CoREST binding at Runx3 locus; flow cytometry of CD8+ T cell subsets in thymus and periphery Scientific reports Medium 25762306
2017 During the restriction point (R-point), Runx3 transiently forms a complex with pRb and Brd2 and induces expression of p21 (Cdkn1a), a key R-point regulator. Cyclin D-CDK4/6 promotes dissociation of the pRb-Runx3-Brd2 complex to turn off p21 expression. Runx3-/- MEFs have dysregulated R-point and form tumors in nude mice; ectopic Runx3 restores R-point control. Runx3-/- mouse embryonic fibroblasts; Co-immunoprecipitation of Runx3-pRb-Brd2 complex; ectopic expression of Runx3 restoring R-point; nude mouse tumorigenicity; Cyclin D1 treatment dissociating complex; K-Ras activation experiments Oncogene High 28846108
2017 TGFβ promotes DNA double-strand breaks (genomic instability) in RUNX3-deficient cancer cells by downregulating the redox regulator heme oxygenase-1 (HO-1/HMOX1), which is a transcriptional target of RUNX3; loss of RUNX3 reduces HO-1, elevates oxidative DNA damage, triggers cellular senescence and SASP. RUNX3 KO/knockdown in cancer cells; TGFβ treatment; measurement of DSBs and oxidative damage; transcriptional analysis of HO-1; SASP assay; tumor genomic instability analysis Cancer research Medium 29074538
2020 G9a (lysine methyltransferase KMT2C) methylates RUNX3 at K129 and K171 under hypoxia; G9a interacts with the RUNX3 Runt domain. This methylation inactivates RUNX3 transcriptional activity by reducing interactions with CBFβ and p300 cofactors, reducing p300-mediated RUNX3 acetylation, and impairing nuclear import via importin-α1, thereby promoting cancer cell proliferation and suppressing apoptosis. Co-immunoprecipitation of G9a-RUNX3; in vitro methylation assay; mass spectrometry identification of methylation sites K129/K171; domain mapping; interaction assays with CBFβ and p300; importin-α1 interaction; cell proliferation and apoptosis assays Cell death and differentiation High 33116296
2007 Runx3 interacts with DNA repair protein Ku70; the interaction was identified by proteomic pulldown and confirmed by His-tag in vitro pulldown. The interaction domain maps to amino acids 241-322 of Runx3 (transcriptional activation domain) and amino acids 1-116 of Ku70. Ku70 knockdown increases Runx3-driven p21 transcription, suggesting Ku70 modulates Runx3 transcriptional activity. Affinity purification of MEF-tagged Runx3 complex + mass spectrometry; His-tag in vitro pulldown; co-immunoprecipitation in vivo; domain deletion mapping; siRNA knockdown of Ku70 with p21 reporter; confocal immunocytochemistry Experimental cell research Medium 17662272
2007 Runx3 directly binds the Osterix (Sp7) promoter at a RUNX binding site (-713 to -707 bp) and transcriptionally represses Osterix expression in dental pulp cells; mutation of this site abolishes repression. Confirmed by EMSA and ChIP in mouse dental pulp cells. Luciferase reporter assay with Osterix promoter in HEK293T cells; promoter site-directed mutagenesis; EMSA; ChIP in mouse dental pulp cells The Biochemical journal High 17352693
2006 RUNX3 negatively regulates CD36 expression in myeloid cells; RUNX3 binds two functional RUNX-binding elements in the CD36 gene proximal regulatory region in vitro and in vivo (ChIP), and overexpression of RUNX3 drastically reduces CD36 expression. EMSA identifying RUNX binding sites in CD36 promoter; ChIP showing RUNX3 occupancy at CD36 regulatory region; RUNX3 overexpression in myeloid cells with CD36 protein measurement Journal of immunology Medium 16887969
2012 RUNX3 negatively regulates ICAM-3 gene expression in myeloid cells during macrophage differentiation and monocyte extravasation; RUNX3 occupies RUNX cognate sequences in the ICAM-3 promoter in vivo, and disruption of RUNX-binding sites or siRNA-mediated reduction of RUNX3 results in increased ICAM-3 mRNA levels. ICAM-3 promoter luciferase assay; ChIP showing RUNX occupancy; siRNA knockdown of RUNX3 with ICAM-3 mRNA quantification; RUNX binding site mutagenesis PloS one Medium 22479382
2014 RUNX3 suppresses gastric cancer cell invasion and vimentin expression by transcriptionally activating miR-30a, which directly targets the 3' UTR of vimentin; miR-30a inhibitor abrogates RUNX3-mediated suppression of invasion and vimentin downregulation. RUNX3 overexpression and knockdown; invasion assays; Western blot for vimentin; miR-30a quantification; 3'UTR luciferase reporter for vimentin-miR-30a targeting; miR-30a inhibitor rescue experiments; nude mouse colonization assay Journal of cellular and molecular medicine Medium 24447545
2017 RUNX3 directly binds the promoter region of miR-182 (confirmed by ChIP) and transcriptionally suppresses it; miR-182 directly targets HOXA9. Thus, RUNX3 inhibits gastric cancer cell proliferation and metastasis via the miR-182/HOXA9 axis. ChIP showing RUNX3 binding to miR-182 promoter; luciferase reporter for HOXA9 as miR-182 target; overexpression/knockdown of RUNX3; rescue experiments with miR-182 mimics; in vivo xenograft mouse model Biomedicine & pharmacotherapy Medium 29054094
2015 Loss of osteoblast-specific Runx3 causes severe congenital osteopenia; Runx3 is expressed in precommitted embryonic osteoblasts and is required for osteoblast proliferation (not apoptosis) to generate adequate numbers of active osteoblasts. Osteoblast-specific Runx3 (Col1α1-cre) but not chondrocyte-specific (Col1α2-cre) KO mice are osteopenic. Conditional Runx3 KO mice with Col1α1-Cre and Col1α2-Cre drivers; bone histomorphometry; primary osteoblast culture proliferation assays; transcriptome analysis of Runx3-null bone Molecular and cellular biology High 25605327
2019 RUNX3 directly interacts with GLI1 and promotes its ubiquitination by E3 ligase β-TrCP, thereby inhibiting Hedgehog signaling and suppressing cancer stem cell properties and metastasis in colorectal cancer. Co-immunoprecipitation of RUNX3-GLI1; ubiquitination assay; β-TrCP identification as the E3 ligase; inverse correlation of RUNX3 and GLI1 in CRC tissues; functional assays for stemness and metastasis Cell death and differentiation Medium 31278361
2005 RUNX3 regulates expression of CD11a (LFA-1) and CD49d (VLA-4) integrin gene promoters; RUNX3 overexpression leads to enhanced CD11a/CD18 levels, and RUNX3 transactivates the CD49d gene promoter through RUNX-binding elements. Luciferase reporter assays for CD11a and CD49d promoters; RUNX3 overexpression; correlation of RUNX3 mRNA with CD49d during dendritic cell maturation Immunobiology Low 16164020
2021 Runx1 and Runx3 are coexpressed in single pro-T cells, bind highly overlapping genomic sites, and have redundant collaborative functions in T cell lineage commitment; they preferentially activate T-lineage genes and repress multipotent progenitor genes at stage-specific loci, shifting binding sites extensively during commitment. Single and double Runx1/Runx3 CRISPR/Cas9 knockouts in pro-T cells; ChIP-seq mapping of Runx1 and Runx3 binding sites across stages; gene expression profiling; partner factor cobinding analysis Proceedings of the National Academy of Sciences of the United States of America High 33479171
2022 Runx3 protects adult articular chondrocytes by transcriptionally driving lubricin and aggrecan expression; Runx3-knockout mice show accelerated osteoarthritis with decreased lubricin and aggrecan. Intra-articular administration of Runx3 adenovirus ameliorated surgically induced osteoarthritis. Runx3-KO mice with surgical OA induction; Runx2 conditional KO mice; comprehensive transcriptional analysis identifying lubricin and aggrecan as Runx3 target genes; intra-articular adenoviral Runx3 delivery Nature communications High 36261443
2020 RUNX3 overexpression in MDS suppresses RUNX1 and its target genes (Cebpa, Csf1r) by binding and remodeling their Runx1-binding regions in Tet2-deficient cells; RUNX3 also activates Myc target genes. In a Tet2-deficient mouse model, RUNX3 overexpression drives MDS-like disease. RUNX3-expressing Tet2-deficient mouse model; ChIP-seq of RUNX3 at Runx1 target gene loci; gene expression analysis; pharmacological MYC-MAX inhibition showing sensitivity Cancer research High 32341038
2017 MYC transcriptionally drives RUNX3 expression in NK/T-cell lymphoma (NKTL) by binding to the RUNX3 enhancer region; ChIP-qPCR confirmed MYC binding to the RUNX3 enhancer, and co-transfection of MYC with RUNX3 enhancer reporter activated transcription. In NKTL, RUNX3 has oncogenic function promoting proliferation and survival. ChIP-qPCR showing MYC binding at RUNX3 enhancer; luciferase reporter assay with RUNX3 enhancer + MYC co-transfection; MYC inhibitor (JQ1) treatment; RUNX3 silencing with apoptosis/proliferation readout Leukemia Medium 28119527
2024 Endothelial RUNX3 maintains liver sinusoidal endothelial cell (LSEC) function; endothelial Runx3-deficient mice develop spontaneous liver fibrosis via IL-6/JAK/STAT3 pathway activation. RUNX3-deficient LSECs secrete LRG1, which activates hepatic stellate cells through TGFBR1-SMAD2/3 signaling in a paracrine manner. Endothelial-specific Runx3 KO mice (spontaneous fibrosis phenotype); single-cell RNA sequencing of liver; in vitro LSEC mechanistic studies; co-culture experiments with LRG1 and HSCs; TGFBR1-SMAD2/3 signaling assays; clinical LRG1 measurement in patients Hepatology High 39042837
2013 Thrombospondin-1 (TSP-1) is a transcriptional target of Runx3; Runx3 expression strongly induces TSP-1 at both mRNA and protein levels in B16-F10 melanoma cells, and Runx3 binds the TSP-1 promoter and stimulates reporter activity. PCR-based cDNA subtraction identifying TSP-1 upregulation by Runx2/Runx3; TSP-1 promoter luciferase reporter assay; Western blot and RT-PCR for TSP-1 upon Runx3 expression in melanoma cells International journal of molecular sciences Low 23846726
2023 RUNX3 induces ferroptosis in gallbladder cancer by activating ING1 transcription (confirmed by ChIP and dual-luciferase assay), which then represses SLC7A11 in a p53-dependent manner; DNMT1-mediated methylation of the RUNX3 promoter silences this pathway. Bisulfite sequencing PCR; dual-luciferase reporter assay; ChIP assay for RUNX3 at ING1 promoter; gain- and loss-of-function assays; in vitro and in vivo ferroptosis assays Cellular signalling Medium 37156453
2023 Runx3-expressing vagal sensory neuron subtypes (co-expressing Prox2 and Runx3) innervate the esophagus as intraganglionic laminar endings and are low-threshold mechanoreceptors; genetic ablation of Prox2/Runx3 neurons abolishes esophageal peristalsis in freely behaving mice. Genetically guided anatomical tracing; optogenetics; electrophysiology; genetic ablation of Prox2/Runx3-expressing neurons with esophageal motility readout Neuron High 37192624
2019 Runx3 controls muscle-specific aspects of sensorimotor circuit formation; conditional inactivation of Runx3 in proprioceptive sensory neurons (PSNs) after peripheral innervation reveals that Runx3 maintains PSN subgroup cell identity and controls sensorimotor connections with muscle-by-muscle variable sensitivity. Target muscles and neurotrophin-3 signaling are required to maintain Runx3 expression in PSNs. Conditional Runx3 inactivation in PSNs after peripheral innervation; anatomical tracing of sensorimotor connections; NT-3 signaling perturbation; in situ hybridization and immunohistochemistry Development (Cambridge, England) Medium 31575648
2004 RUNX3 reinstates TGF-β responsiveness in Barrett's-derived esophageal adenocarcinoma cells (SEG-1) that lack RUNX3; transfection of RUNX3 restores Smad-mediated TGF-β transcriptional activity and enables TGF-β-induced antiproliferation and apoptosis. RUNX3 transfection into SEG-1 cells; dual-luciferase assay for Smad-mediated TGF-β transcription; proliferation and apoptosis assays with TGF-β treatment Surgery Medium 15300196
2018 RUNX1 and RUNX3 interact with YAP (Hippo pathway effector) and act as negative regulators of its oncogenic function; RUNX1/RUNX3 inhibit YAP-mediated migration and stemness in mammary epithelial cells in an interaction-dependent manner and co-regulate YAP-mediated gene expression. Co-immunoprecipitation of RUNX1/RUNX3 with YAP; RUNX1/RUNX3 overexpression with YAP; migration and stemness assays in mammary epithelial cell lines; gene expression profiling Oncotarget Medium 29581836
2010 miR-130b directly targets and downregulates RUNX3 protein in gastric cancer cells, reducing TGF-β-mediated apoptosis (via Bim) and increasing cell viability; demonstrated by luciferase reporter assay and Western blot. Bioinformatic prediction + luciferase reporter assay for miR-130b targeting RUNX3 3'UTR; miR-130b precursor/inhibitor transfection; cell viability, apoptosis, and Bim expression assays European journal of cancer Medium 20176475
2007 Runx3 is expressed in early and late chondrocyte differentiation and transcriptionally inhibits Runx1 expression in chondrocytes; Runx3 gain and loss of function regulates both early and late markers of chondrocyte maturation. Real-time RT-PCR of Runx3 in embryonic development; Runx3 overexpression and siRNA knockdown in chondrogenic cell lines; luciferase reporter assay of Runx1 promoter driven by Runx3 Journal of bone and mineral research Medium 17488194
2006 RUNX3 protein is frequently mislocalized to the cytoplasm in breast cancer (35/44 primary tumors), which is a distinct mechanism of inactivation separate from promoter hypermethylation; cytoplasmic RUNX3 cannot perform its growth-suppressive function. Stable nuclear RUNX3 expression in MDA-MB-231 cells reduced invasiveness and tumor formation. IHC and subcellular fractionation of RUNX3 in primary breast cancer specimens; stable RUNX3 expression in MDA-MB-231 cells; Matrigel invasion assay; nude mouse tumor formation assay Cancer research Medium 16818622
2018 Runx3 regulates folliculogenesis and steroidogenesis in ovarian granulosa cells; Runx3-/- mice have reduced primary and antral follicles, decreased expression of activin/inhibin subunits (Inha, Inhba, Inhbb), and decreased steroidogenic enzyme genes Cyp11a1 and Cyp19a1. Cultured Runx3-/- granulosa cells show impaired FSH-induced Cyp19a1 induction. Runx3 knockout mice (ovarian histology and follicle counting); gene expression analysis by qPCR in ovaries; primary granulosa cell culture with FSH treatment Cell and tissue research Medium 30377784

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 896 11955451
2017 Runx3 programs CD8+ T cell residency in non-lymphoid tissues and tumours. Nature 548 29211713
2004 Runx2 and Runx3 are essential for chondrocyte maturation, and Runx2 regulates limb growth through induction of Indian hedgehog. Genes & development 479 15107406
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 318 12796513
2010 The chemokine CXCL12 regulates monocyte-macrophage differentiation and RUNX3 expression. Blood 259 20930067
2006 RUNX3 is frequently inactivated by dual mechanisms of protein mislocalization and promoter hypermethylation in breast cancer. Cancer research 174 16818622
2009 Transcription factors RUNX1 and RUNX3 in the induction and suppressive function of Foxp3+ inducible regulatory T cells. The Journal of experimental medicine 171 19917773
2010 MicroRNA-130b regulates the tumour suppressor RUNX3 in gastric cancer. European journal of cancer (Oxford, England : 1990) 142 20176475
2005 RUNX3 inactivation by point mutations and aberrant DNA methylation in bladder tumors. Cancer research 131 16230397
2009 Promoter methylation in APC, RUNX3, and GSTP1 and mortality in prostate cancer patients. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 122 19470943
2004 Tumor suppressor activity of RUNX3. Oncogene 111 15156190
2009 Molecular pathology of RUNX3 in human carcinogenesis. Biochimica et biophysica acta 101 19682550
1998 CBF alpha3 (AML2) is induced by TGF-beta1 to bind and activate the mouse germline Ig alpha promoter. Journal of immunology (Baltimore, Md. : 1950) 86 9862705
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
2014 RUNX3 regulates vimentin expression via miR-30a during epithelial-mesenchymal transition in gastric cancer cells. Journal of cellular and molecular medicine 76 24447545
2004 Hemizygous deletion and hypermethylation of RUNX3 gene in hepatocellular carcinoma. World journal of gastroenterology 72 14760761
2009 PTHrP prevents chondrocyte premature hypertrophy by inducing cyclin-D1-dependent Runx2 and Runx3 phosphorylation, ubiquitylation and proteasomal degradation. Journal of cell science 71 19351720
2005 DNA methylation-associated inactivation of TGFbeta-related genes DRM/Gremlin, RUNX3, and HPP1 in human cancers. British journal of cancer 71 16234815
2009 RUNX3 has an oncogenic role in head and neck cancer. PloS one 70 19521519
2006 RUNX3 protein is overexpressed in human basal cell carcinomas. Oncogene 68 16767156
2015 The emerging role of RUNX3 in cancer metastasis (Review). Oncology reports 66 26708741
2018 RUNX1 and RUNX3 protect against YAP-mediated EMT, stem-ness and shorter survival outcomes in breast cancer. Oncotarget 64 29581836
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
2004 Frequent loss of RUNX3 expression by promoter hypermethylation in gastric carcinoma. Pathobiology : journal of immunopathology, molecular and cellular biology 62 15051926
2010 RUNX3 modulates DNA damage-mediated phosphorylation of tumor suppressor p53 at Ser-15 and acts as a co-activator for p53. The Journal of biological chemistry 61 20353948
2022 Runx2 and Runx3 differentially regulate articular chondrocytes during surgically induced osteoarthritis development. Nature communications 60 36261443
2017 RUNX3 is oncogenic in natural killer/T-cell lymphoma and is transcriptionally regulated by MYC. Leukemia 57 28119527
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
2006 Runx3 regulates dendritic epidermal T cell development. Developmental biology 49 17222403
2020 MiR-17-5p promotes cellular proliferation and invasiveness by targeting RUNX3 in gastric cancer. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 48 32447210
2013 Ihh and Runx2/Runx3 signaling interact to coordinate early chondrogenesis: a mouse model. PloS one 48 23383321
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
2015 Loss of osteoblast Runx3 produces severe congenital osteopenia. Molecular and cellular biology 46 25605327
2009 Runt-related transcription factor RUNX3 is a target of MDM2-mediated ubiquitination. Cancer research 46 19808967
2004 RUNX3 inhibits cell proliferation and induces apoptosis by reinstating transforming growth factor beta responsiveness in esophageal adenocarcinoma cells. Surgery 46 15300196
2019 miR-301a promotes lung tumorigenesis by suppressing Runx3. Molecular cancer 45 31122259
2007 Promoter hypermethylation of the RUNX3 gene in esophageal squamous cell carcinoma. Cancer investigation 45 18058463
2023 Epigenetic reprogramming of Runx3 reinforces CD8 + T-cell function and improves the clinical response to immunotherapy. Molecular cancer 44 37189103
2011 Oncogenic role of RUNX3 in head and neck cancer. Journal of cellular biochemistry 44 21268058
2004 RUNX3 expression in primary and metastatic pancreatic cancer. Journal of clinical pathology 42 14990603
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 41 33479171
2011 Association between RUNX3 promoter methylation and gastric cancer: a meta-analysis. BMC gastroenterology 40 21867527
2014 Role of RUNX3 in suppressing metastasis and angiogenesis of human prostate cancer. PloS one 38 24475196
2018 Emerging role of RUNX3 in the regulation of tumor microenvironment. BMB reports 37 29429451
2023 Prox2 and Runx3 vagal sensory neurons regulate esophageal motility. Neuron 35 37192624
2010 Role of RUNX3 in bone morphogenetic protein signaling in colorectal cancer. Cancer research 35 20442291
2018 RUNX3 inhibits glioma survival and invasion via suppression of the β-catenin/TCF-4 signaling pathway. Journal of neuro-oncology 34 29916101
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
2012 RUNX3 regulates intercellular adhesion molecule 3 (ICAM-3) expression during macrophage differentiation and monocyte extravasation. PloS one 31 22479382
2020 RUNX3 methylation drives hypoxia-induced cell proliferation and antiapoptosis in early tumorigenesis. Cell death and differentiation 30 33116296
2010 RUNX3 methylation and expression associated with advanced precancerous gastric lesions in a Chinese population. Carcinogenesis 30 21135153
2020 Transcription factor RUNX3 promotes CD8+ T cell recruitment by CCL3 and CCL20 in lung adenocarcinoma immune microenvironment. Journal of cellular biochemistry 28 31898342
2020 Oncogenic RUNX3: A Link between p53 Deficiency and MYC Dysregulation. Molecules and cells 28 31991537
2017 RUNX3 regulates hepatocellular carcinoma cell metastasis via targeting miR-186/E-cadherin/EMT pathway. Oncotarget 27 28977878
2015 RUNX3 promoter hypermethylation is frequent in leukaemia cell lines and associated with acute myeloid leukaemia inv(16) subtype. British journal of haematology 27 25612675
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
2016 Generation of RUNX3 knockout pigs using CRISPR/Cas9-mediated gene targeting. Reproduction in domestic animals = Zuchthygiene 26 27696566
2005 Analyzing expression of perforin, Runx3, and Thpok genes during positive selection reveals activation of CD8-differentiation programs by MHC II-signaled thymocytes. Journal of immunology (Baltimore, Md. : 1950) 26 16177089
2007 Downregulation of the RUNX3 gene by promoter hypermethylation and hemizygous deletion in breast cancer. Journal of Korean medical science 25 17923751
2006 How does the human RUNX3 gene induce apoptosis in gastric cancer? Latest data, reflections and reactions. Cancer biology & therapy 25 16627973
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 DNA methylation of RUNX3 promotes the progression of gallbladder cancer through repressing SLC7A11-mediated ferroptosis. Cellular signalling 22 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
2021 Oestrogen up-regulates DNMT1 and leads to the hypermethylation of RUNX3 in the malignant transformation of ovarian endometriosis. Reproductive biomedicine online 21 34799276
2014 Lineage-specific RUNX3 hypomethylation marks the preneoplastic immune component of gastric cancer. Oncogene 21 25088199
2006 Lack of RUNX3 regulation in human gastric cancer. The Journal of pathology 21 16917803
2023 RUNX3 in Stem Cell and Cancer Biology. Cells 20 36766749
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
2007 Runx3 negatively regulates Osterix expression in dental pulp cells. The Biochemical journal 20 17352693
2019 Muscle-selective RUNX3 dependence of sensorimotor circuit development. Development (Cambridge, England) 19 31575648
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
2020 Significance of MEF2C and RUNX3 Regulation for Endochondral Differentiation of Human Mesenchymal Progenitor Cells. Frontiers in cell and developmental biology 18 32195247
2017 EZH2 promotes cell proliferation by regulating the expression of RUNX3 in laryngeal carcinoma. Molecular and cellular biochemistry 18 28795320
2005 RUNX3 regulates the activity of the CD11a and CD49d integrin gene promoters. Immunobiology 18 16164020
2018 Runx3 regulates folliculogenesis and steroidogenesis in granulosa cells of immature mice. Cell and tissue research 16 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
2017 Methylation analysis of p16, SLIT2, SCARA5, and Runx3 genes in hepatocellular carcinoma. Medicine 16 29019900
2008 Loss of Runx3 affects ovulation and estrogen-induced endometrial cell proliferation in female mice. Molecular reproduction and development 16 18361415
2007 Balance of NF-kappaB and p38 MAPK is a determinant of radiosensitivity of the AML-2 and its doxorubicin-resistant cell lines. Leukemia research 16 17218010
2024 Endothelial RUNX3 controls LSEC dysfunction and angiocrine LRG1 signaling to prevent liver fibrosis. Hepatology (Baltimore, Md.) 15 39042837
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