Affinage

PBX3

Pre-B-cell leukemia transcription factor 3 · UniProt P40426

Length
434 aa
Mass
47.2 kDa
Annotated
2026-06-10
94 papers in source corpus 32 papers cited in narrative 32 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

PBX3 is a TALE-class homeodomain transcription factor that assembles hetero-oligomeric DNA-binding complexes with homeodomain partners to control developmental and oncogenic transcriptional programmes (PMID:1682799, PMID:25911551). It is highly homologous to PBX1 and is alternatively spliced into isoforms with distinct partner-binding properties; canonical PBX3A/B engage PREP1 and MEIS proteins, whereas leukemia-favored isoforms lose these interactions (PMID:1682799, PMID:11579467). In development, Pbx3 partners with the metaHox factor Rnx (Tlx3) to support medullary respiratory neuron function, with loss causing fatal neonatal respiratory failure (PMID:15466398), and is required caudal to the hindbrain for correct specification and positioning of dorsal horn interneurons (PMID:18155191); it also directly binds an intronic SHH cis-regulatory element to repress SHH transcription, acting opposite to PBX1 at the same element (PMID:40397886). In leukemia, PBX3 is a selective HOXA9 cofactor whose depletion blocks MLL-fusion transformation, and PBX3/MEIS1 co-expression transforms hematopoietic progenitors and drives AML even without ectopic HOX by re-activating endogenous Hoxa genes (PMID:23264595, PMID:26747896); mechanistically, PBX3 binds and stabilizes MEIS1 against ubiquitin-proteasome degradation while also inducing MEIS1 transcription and forming high-affinity Hoxa9/Meis1/Pbx3 DNA complexes (PMID:25911551). PBX3 sustains leukemia stem cells, and its locus is epigenetically activated through elevated H3K79me2, while it suppresses type I interferon response genes during AML progression (PMID:28411381, PMID:30214626, PMID:40108441). Across solid tumors PBX3 acts as a sequence-specific promoter-binding regulator that activates metabolic and oncogenic genes (G6PD, HMGCR, CA9) and represses tumor-suppressive genes (p53, TET2), thereby reprogramming metabolism and survival (PMID:37781025, PMID:40508020, PMID:40048803, PMID:33526870, PMID:39668567). Its abundance is set post-transcriptionally by multiple 3'-UTR-targeting miRNAs and by RNA-binding/stability and deubiquitination pathways (DDX54, LIN28B, ATRAP/USP14) (PMID:26420065, PMID:32712782, PMID:39668567, PMID:35414770).

Mechanistic history

Synthesis pass · year-by-year structured walk · 27 steps
  1. 1991 High

    Established PBX3's molecular identity as a TALE-class homeodomain factor closely related to PBX1 and revealed alternative splicing generating products with distinct C-termini, the structural basis for later isoform-specific functions.

    Evidence Molecular cloning, sequence analysis, and Northern blot

    PMID:1682799

    Open questions at the time
    • No DNA-binding partners or target genes identified at this stage
    • Functional consequences of the two isoforms not tested
  2. 2001 Medium

    Defined that alternative splicing controls partner specificity, with novel isoforms (PBX3C/D) failing to bind PREP1 and binding MEIS only weakly, linking isoform choice to normal versus leukemic contexts.

    Evidence RT-PCR isoform identification and co-immunoprecipitation interaction assays

    PMID:11579467

    Open questions at the time
    • Functional transcriptional output of each isoform not measured
    • Mechanism driving isoform switching in leukemia unknown
  3. 2004 High

    Demonstrated an essential developmental role: Pbx3 partners with Rnx/Tlx3 to enable TALE-complex transcriptional activity required for medullary respiratory circuit function.

    Evidence Pbx3-knockout mice with respiratory phenotype plus in vitro transcription and DNA-binding complex assays

    PMID:15466398

    Open questions at the time
    • Direct target genes of the Pbx3/Rnx complex not identified
    • Whether the same complex operates outside the medulla untested
  4. 2004 Medium

    Showed PBX3 is regulated post-transcriptionally and as a partner stabilizer, with retinoic acid extending its protein half-life and decreasing proteasomal PBX degradation in association with MEIS.

    Evidence P19 differentiation model with cycloheximide chase, half-life assay, and MEIS co-IP

    PMID:15095411

    Open questions at the time
    • E3 ligase mediating PBX degradation not identified
    • Direct versus indirect RA effect on PBX3 transcription unresolved
  5. 2007 High

    Extended the developmental requirement to spinal cord, showing Pbx3 controls specification and positioning of dorsal horn glutamatergic interneurons.

    Evidence Conditional knockout mouse with immunohistochemistry and neuroanatomical marker analysis

    PMID:18155191

    Open questions at the time
    • Transcriptional targets driving interneuron identity not defined
    • Partner factors in this context not identified
  6. 2012 High

    Identified PBX3 as a selective, non-redundant HOXA9 cofactor in leukemogenesis, distinguishing it from PBX1/PBX2 and nominating the HOX-PBX interface as a therapeutic target.

    Evidence shRNA depletion, retroviral co-expression, in vitro transformation, mouse leukemia model, and HXR9 peptide disruption

    PMID:23264595

    Open questions at the time
    • Genome-wide PBX3/HOXA9 target loci not mapped here
    • Structural basis of PBX3 selectivity over PBX1/2 not defined
  7. 2015 High

    Resolved the mechanism of PBX3-MEIS1 cooperation: PBX3 binding stabilizes otherwise degradation-prone MEIS1, induces its transcription, and forms high-affinity Hoxa9/Meis1/Pbx3 DNA complexes.

    Evidence Deletion mapping, co-IP, MG132 proteasome inhibition, half-life measurement, in vitro DNA-complex assembly, and transplantation assays

    PMID:25911551

    Open questions at the time
    • E3 ligase targeting MEIS1 not identified
    • Whether PBX3 stabilizes other partners similarly untested
  8. 2015 High

    Showed PBX3 is a hub of post-transcriptional control and a driver of cancer stemness, repressed cooperatively by multiple 3'-UTR miRNAs and required for hepatocellular tumor-initiating cell programmes.

    Evidence miRNA gain/loss, luciferase 3'-UTR reporters, shRNA knockdown with rescue, and TIC functional and expression profiling

    PMID:26420065

    Open questions at the time
    • Direct versus indirect regulation of CACNA2D1/EpCAM/SOX2/NOTCH3 not all distinguished
    • Cofactor requirements in HCC TICs not defined
  9. 2016 High

    Demonstrated PBX3/MEIS1 co-expression alone, without ectopic HOX, transforms progenitors and recapitulates the MLL-fusion core transcriptome by re-activating endogenous Hoxa genes.

    Evidence Retroviral co-expression, transformation and AML mouse models, expression profiling, and interface-disruption mutants

    PMID:26747896

    Open questions at the time
    • How PBX3/MEIS1 induce endogenous Hoxa transcription mechanistically not resolved
    • Direct genomic binding sites not mapped
  10. 2017 High

    Linked PBX3 to leukemia stem cell maintenance and to its own epigenetic activation, with CRISPR deletion reducing LSC capacity and aberrant H3K79me2 gain at the Pbx3 locus.

    Evidence CRISPR/Cas9 deletion, AML transplantation, flow cytometry LSC analysis, and ChIP-seq/qPCR of histone marks

    PMID:28411381

    Open questions at the time
    • Causal writer of H3K79me2 at Pbx3 not functionally tested here
    • Downstream LSC survival effectors not defined
  11. 2014 Medium

    In solid tumors, established PBX3 as a pro-migratory/invasive factor acting in part through MAPK/ERK activation.

    Evidence Forced expression/knockdown with migration and invasion assays and p-ERK1/2 immunoblot

    PMID:25561793

    Open questions at the time
    • Direct transcriptional targets in CRC migration not identified
    • Whether ERK activation is direct or transcriptionally relayed unknown
  12. 2016 Medium

    Connected PBX3 to EMT-driven invasion in gastric cancer via AKT activation and MMP-9 induction.

    Evidence Gain/loss-of-function with EMT and p-AKT immunoblots, gelatin zymography, and xenografts

    PMID:27900025

    Open questions at the time
    • Direct promoter targets among EMT genes not shown
    • Mechanism of AKT activation not defined
  13. 2018 Medium

    Positioned PBX3 downstream of WNT/SNAIL/ZEB1 via miR-200, integrating it into EMT regulatory circuitry in colorectal cancer.

    Evidence Reporter assays, transcriptomics, miRNA manipulation, siRNA knockdown, and in situ hybridization

    PMID:29391352

    Open questions at the time
    • Direct miR-200 targeting of PBX3 in this context vs indirect not fully resolved
    • PBX3 effector genes for EMT not mapped
  14. 2018 Medium

    Defined a PBX3-MEK/ERK/c-Myc-LIN28-let-7 positive feedback loop driving glioblastoma mesenchymal transition.

    Evidence ChIP, dual-luciferase reporter, shRNA/overexpression, orthotopic model, and TGFbeta stimulation

    PMID:30016974

    Open questions at the time
    • Quantitative contribution of each loop node not dissected
    • Generalizability beyond GBM untested
  15. 2020 Medium

    Identified RNA-stability feedback regulating PBX3 mRNA, with PBX3 activating lncRNA SNHG10 which recruits DDX54 to stabilize PBX3 transcripts.

    Evidence ChIP at the SNHG10 promoter, luciferase reporter, RIP, and RNA pull-down

    PMID:32712782

    Open questions at the time
    • DDX54 binding site on PBX3 mRNA not mapped
    • Stoichiometry/kinetics of the feedback loop unknown
  16. 2021 Medium

    Showed PBX3 directly represses the p53 promoter to lower p21 and enable proliferation, establishing a direct tumor-suppressor-repression mechanism.

    Evidence ChIP at the p53 promoter, luciferase reporter, siRNA knockdown, and cell-cycle/apoptosis assays

    PMID:33526870

    Open questions at the time
    • Cofactors enabling repression not identified
    • Direct binding motif within p53 promoter not defined
  17. 2021 Medium

    Connected PBX3 to leptin/STAT3-driven endocrine therapy resistance through FGFR1 transactivation requiring the MTA1-HDAC2 complex.

    Evidence PDX, STAT3 inhibition, gain/loss-of-function, microarray, and co-IP of PBX3-MTA1-HDAC2

    PMID:33608482

    Open questions at the time
    • Direct PBX3 binding at FGFR1 not shown by ChIP here
    • Whether MTA1-HDAC2 association is direct unresolved
  18. 2021 Medium

    Implicated PBX3 in non-cancer pathology, directly activating TOP2A to regulate mast cell DNA damage, senescence, and parthanatos in allergic rhinitis.

    Evidence ChIP at the TOP2A promoter, shRNA knockdown, mouse AR model, and mitochondrial assays

    PMID:42006311

    Open questions at the time
    • Upstream regulator of PBX3 in mast cells not defined
    • Direct binding motif not characterized
  19. 2021 Medium

    Placed Pbx3 downstream of purinergic P2X7 signaling in MLL-rearranged AML, accounting for P2X7's pro-leukemic and LSC-promoting effects.

    Evidence shRNA knockdown, AML mouse and PDX models, and P2X7 antagonist treatment

    PMID:32165482

    Open questions at the time
    • Mechanism linking P2X7 to Pbx3 transcription not defined
    • Direct versus indirect upregulation unresolved
  20. 2022 Medium

    Extended purinergic control to P2X1, showing ATP-P2X1 signaling upregulates PBX3 which transactivates BCAT1 to maintain leukemia-initiating cell fate.

    Evidence P2X1 deletion AML model, phospho-site mutagenesis, expression analysis, ChIP of PBX3 at BCAT1, and antagonist treatment

    PMID:36418376

    Open questions at the time
    • Signaling intermediates between P2X1 and PBX3 not mapped
    • Metabolic consequence of BCAT1 induction not fully quantified
  21. 2022 Medium

    Defined a deubiquitination-based stabilization mechanism in which ATRAP directs USP14 to deubiquitinate and stabilize PBX3 protein, activating AKT/mTOR.

    Evidence Co-IP of ATRAP-PBX3 and USP14-PBX3, ubiquitination and stability assays, and functional assays

    PMID:35414770

    Open questions at the time
    • E3 ligase counteracting USP14 not identified
    • Ubiquitination sites on PBX3 not mapped
  22. 2022 Low

    Reported PBX3 as a transcriptional activator of lncRNA DLG1-AS1 in triple-negative breast cancer.

    Evidence ChIP at the DLG1-AS1 promoter, luciferase reporter, and TNBC functional assays

    PMID:35592389

    Open questions at the time
    • ChIP-only without mutagenesis or reconstitution
    • Downstream consequence of DLG1-AS1 induction not defined
  23. 2023 Medium

    Showed PBX3 directly activates G6PD to fuel the pentose phosphate pathway, increasing NADPH/nucleotide output and lowering ROS to support tumorigenesis.

    Evidence ChIP at the G6PD promoter, luciferase reporter, metabolic assays, and xenografts

    PMID:37781025

    Open questions at the time
    • Partner factors at the G6PD promoter not identified
    • Tissue specificity of this metabolic axis untested
  24. 2024 Medium

    Identified an mRNA-stability input from PHAX/LIN28B feeding into PBX3 protein, which directly represses TET2 to promote esophageal cancer proliferation and block apoptosis/autophagy.

    Evidence Co-IP of PHAX-LIN28B, mRNA stability assay, ChIP at TET2 promoter, luciferase reporter, and mouse tumor model

    PMID:39668567

    Open questions at the time
    • LIN28B binding element on PBX3 mRNA not mapped
    • Repressive cofactors at TET2 not identified
  25. 2025 High

    Established a developmental repressive role at SHH, with PBX3 binding the intronic SFE1 element to repress SHH transcription, directly opposing PBX1 at the same element.

    Evidence RCAS overexpression/knockdown in chick, ChIP-seq, ATAC-seq, luciferase reporter, and in ovo electroporation

    PMID:40397886

    Open questions at the time
    • Molecular basis of PBX3 vs PBX1 opposite activity at SFE1 not defined
    • Partner specificity at this element not resolved
  26. 2025 Medium

    Linked PBX3 to immune evasion in AML by suppressing type I interferon response genes, partially counteracting IFN-induced leukemic differentiation.

    Evidence CRISPR-mediated MLL-AF9 translocation model, in vivo progression, IFNalpha treatment, and expression analysis

    PMID:40108441

    Open questions at the time
    • Direct PBX3 targets among IFN-response genes not mapped
    • Mechanism of IFN suppression not defined
  27. 2025 Medium

    Added an m6A input controlling PBX3, with METTL3 modifying PBX3 mRNA and PBX3 directly activating CA9 to suppress ferroptosis in esophageal squamous carcinoma.

    Evidence MeRIP of PBX3 mRNA, ChIP at the CA9 promoter, luciferase reporter, ferroptosis assays, and xenograft

    PMID:40048803

    Open questions at the time
    • m6A reader mediating PBX3 upregulation not identified
    • Generality of CA9/ferroptosis axis untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • How PBX3 selects between transcriptional activation and repression at different promoters, and which partners and chromatin contexts determine this switch genome-wide, remains unresolved.
  • No comprehensive genome-wide PBX3 binding atlas across tissues
  • Structural basis of isoform- and partner-dependent activity undefined
  • Determinants of activation vs repression at direct targets unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 7 GO:0003677 DNA binding 5 GO:0140313 molecular sequestering activity 1
Localization
GO:0005634 nucleus 2
Pathway
R-HSA-74160 Gene expression (Transcription) 5 R-HSA-1266738 Developmental Biology 3 R-HSA-1643685 Disease 3
Partners
HDAC2HOXA9MEIS1MTA1PREP1TLX3USP14
Complex memberships
Hoxa9/Meis1/Pbx3 DNA-binding complexPBX3-MTA1-HDAC2 complexPbx3/Rnx(Tlx3) TALE complex

Evidence

Reading pass · 32 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1991 PBX3 is a TALE-class homeodomain transcription factor with 94% identity to PBX1 over 266 amino acids spanning and flanking the homeodomain. PBX3 mRNA is alternatively spliced to yield two translation products with different carboxy termini, a feature shared with PBX1 but not PBX2. Molecular cloning, sequence analysis, Northern blot (alternative splicing) Molecular and cellular biology High 1682799
2004 Pbx3-deficient mice die within hours of birth from central respiratory failure due to abnormal inspiratory neuron activity in the medulla oblongata. Pbx3 forms a DNA-binding complex with the metaHox transcription factor Rnx (Tlx3), and in the absence of Pbx3, Rnx's ability to enhance transcription in vitro as part of a TALE-protein complex is abolished, though Rnx expression itself is unaffected. Knockout mouse (Pbx3-deficient), in vitro transcription assay, co-immunoprecipitation / DNA-binding complex formation The American journal of pathology High 15466398
2001 Two novel PBX3 isoforms (PBX3C and PBX3D) generated by alternative splicing are unable to interact with the PBX-interacting factor PREP1 and interact only weakly with MEIS proteins, in contrast to canonical PBX3A/B isoforms. PBX3C expression is favored in leukemia cells whereas PBX3D predominates in normal cells. RT-PCR (isoform identification), co-immunoprecipitation / interaction assays (functional binding studies) Genes, chromosomes & cancer Medium 11579467
2004 Retinoic acid increases PBX3 mRNA levels as a secondary (not primary) transcriptional response requiring new protein synthesis, and retinoic acid treatment also significantly extends PBX3 protein half-life. PBX proteins associate with RA-dependent increased MEIS protein levels, and RA may decrease proteasome-dependent PBX protein degradation. P19 cell differentiation model, cycloheximide chase (mRNA stability), protein half-life assay, co-immunoprecipitation with MEIS proteins Journal of cellular biochemistry Medium 15095411
2007 Conditional loss of Pbx3 caudal to the hindbrain leads to progressive locomotion and posture deficits, reduced dorsal horn size, and loss of calbindin-, PKC-gamma-, and calretinin-expressing neurons in laminae I–III. In embryonic dorsal horn, Pbx3 is expressed in a subset of glutamatergic neurons; its absence causes incorrect specification of some glutamatergic neurons and abnormal positioning of Meis+ glutamatergic neurons. Conditional knockout mouse, immunohistochemistry, cell counting, neuroanatomical analysis Developmental biology High 18155191
2012 PBX3 (but not PBX1 or PBX2) acts as a critical cofactor of HOXA9 in leukemogenesis: shRNA depletion of Pbx3 significantly inhibits MLL-fusion-mediated cell transformation, and co-expression of PBX3 with HOXA9 synergistically promotes cell transformation in vitro and AML in vivo. The small peptide HXR9, which disrupts HOX-PBX interactions, selectively kills leukemic cells with HOXA/PBX3 overexpression. shRNA knockdown, retroviral overexpression, in vitro transformation assay, mouse leukemia model, HXR9 peptide treatment Blood High 23264595
2015 Pbx3 and Meis1 must dimerize to support Hox-induced leukemia. In the absence of Pbx3, Meis1 protein is highly unstable and undergoes ubiquitin-proteasome-mediated degradation via a motif coinciding with the Pbx-binding domain; binding to Pbx3 or deletion of this motif prolongs Meis1 half-life. Additionally, Pbx3 overexpression induces endogenous Meis1 transcription. Meis1 binding to Pbx3 is required to form high-affinity DNA/Hoxa9/Meis1/Pbx3 complexes in vitro. Deletion analysis, co-immunoprecipitation, ubiquitin-proteasome inhibitor assay (MG132), protein half-life measurement, in vitro DNA-binding complex formation, colony-forming assay, transplantation assay Haematologica High 25911551
2015 PBX3 is targeted synergistically by let-7c, miR-200b, miR-222, and miR-424 at its 3'-UTR, and is both sufficient and necessary for the acquisition and maintenance of HCC tumor-initiating cell (TIC) properties. PBX3 drives a transcriptional programme activating CACNA2D1, EpCAM, SOX2, and NOTCH3 expression in HCC TICs. miRNA overexpression/inhibition, luciferase 3'-UTR reporter assay, shRNA knockdown, TIC functional assays (sphere formation, tumorigenicity), rescue experiments, gene expression profiling Nature communications High 26420065
2016 Co-expression of PBX3 and MEIS1 (without ectopic HOX) is sufficient to transform normal mouse hematopoietic stem/progenitor cells and cause AML in vivo. PBX3/MEIS1 overexpression recapitulates the MLL-fusion core transcriptome including upregulation of endogenous Hoxa genes. Disruption of the MEIS1-PBX3 binding interface abolishes transformation and HOX gene upregulation. Retroviral co-expression, in vitro transformation assay, mouse AML model, gene expression profiling, binding-interface disruption mutants Cancer research High 26747896
2014 PBX3 promotes migration and invasion of colorectal cancer cells partially through activation of the MAPK/ERK signaling pathway, as evidenced by upregulation of phosphorylated ERK1/2 upon PBX3 overexpression. Forced expression and shRNA knockdown, wound-healing assay, Boyden chamber assay, Western blot (p-ERK1/2) World journal of gastroenterology Medium 25561793
2016 PBX3 promotes gastric cancer invasion and metastasis by inducing EMT (increased N-cadherin and vimentin, decreased E-cadherin) and activating AKT (increased p-AKT Ser473) and MMP-9 activity. Overexpression/knockdown, Western blot (EMT markers, p-AKT), gelatin zymography (MMP-9), nude mouse xenograft Oncology letters Medium 27900025
2017 Pbx3 deletion via CRISPR/Cas9 in MLL-AF9 AML mouse model significantly prolongs survival and decreases leukemia burden by reducing leukemia stem cell (LSC) capacity and promoting LSC apoptosis. ChIP-seq/qPCR in MLL-rearranged mouse models revealed aberrant epigenetic modifications with increased H3K79me2 and decreased H3K9me3 and H3K27me3 at Pbx3 loci in LSCs. CRISPR/Cas9 deletion, mouse AML model transplantation, flow cytometry (LSC analysis), ChIP-seq/qPCR (histone modifications) International journal of cancer High 28411381
2018 PBX3 expression in colorectal cancer is induced by WNT pathway activation and by EMT transcription factors SNAIL and ZEB1, with these effects mediated indirectly through microRNA miR-200. PBX3 is required for a full EMT phenotype in colon cancer cells. Reporter assays, transcriptomic analysis, miRNA manipulation, siRNA knockdown, in situ hybridization Clinical cancer research Medium 29391352
2018 PBX3 promotes GBM mesenchymal transition through activation of MEK/ERK1/2 signaling, leading to increased c-Myc-dependent LIN28 expression. LIN28 then inhibits let-7b biogenesis; let-7b suppresses PBX3 by targeting its 3'-UTR, forming a positive feedback loop. ChIP experiments confirmed PBX3-driven transcriptional activation of LIN28 via MEK/ERK/c-Myc. Western blot, ChIP, dual-luciferase reporter assay, shRNA/overexpression, orthotopic mouse model, TGFβ stimulation Journal of experimental & clinical cancer research Medium 30016974
2021 PBX3 binds to the p53 promoter and suppresses its transcriptional activity, thereby reducing p21 expression and enabling tumor cell proliferation. PBX3 silencing induces p21 expression and increases apoptosis in colorectal cancer cells. ChIP (PBX3 binding to p53 promoter), luciferase reporter assay, siRNA knockdown, cell cycle/apoptosis analysis Acta pharmacologica Sinica Medium 33526870
2023 PBX3 directly binds to the G6PD promoter and activates its transcription, stimulating the pentose phosphate pathway (PPP), enhancing NADPH and nucleotide production, decreasing intracellular ROS, and promoting tumorigenic potential in vitro and in vivo. ChIP (PBX3 binding to G6PD promoter), luciferase reporter assay, metabolic assays (NADPH, nucleotide, ROS), xenograft model International journal of biological sciences Medium 37781025
2025 PBX3 directly binds to the HMGCR promoter (-167/-151 region) and increases its transcriptional activity, thereby upregulating cholesterol biosynthesis in HCC cells and enhancing tumorigenic potential in vivo. ChIP (PBX3 binding to HMGCR promoter), luciferase reporter assay, cholesterol biosynthesis measurement, xenograft model International journal of molecular sciences Medium 40508020
2021 PBX3 directly binds to the TOP2A promoter to activate its transcription, regulating mast cell DNA damage, senescence, mitochondrial function, and parthanatos in allergic rhinitis. PBX3 knockdown significantly alleviates AR symptoms in mice. ChIP (PBX3 binding to TOP2A promoter), shRNA knockdown, mouse AR model, mitochondrial membrane potential assay iScience Medium 42006311
2020 lncRNA H19 inhibits CYP1B1 expression by regulating PBX3, which directly binds to the CYP1B1 promoter to control its activity. This H19/PBX3/CYP1B1 axis modulates cardiomyocyte pyroptosis during myocardial infarction. RIP, dual-luciferase reporter assay (H19-PBX3-CYP1B1 axis), overexpression/knockdown, MI rat model Molecular and cellular biochemistry Low 33389498
2020 PBX3 acts as a transcriptional activator of the lncRNA SNHG10 promoter in gastric cancer cells. SNHG10 in turn stabilizes PBX3 mRNA through recruiting the RNA-binding protein DDX54, forming a positive feedback loop. DDX54 was shown by RIP and RNA pull-down to bind both SNHG10 and PBX3 mRNA. ChIP (PBX3 binding to SNHG10 promoter), luciferase reporter assay, RIP, RNA pull-down (DDX54-SNHG10-PBX3 mRNA interaction) Digestive diseases and sciences Medium 32712782
2021 Leptin activates PBX3 expression in a STAT3-dependent manner in breast cancer cells. PBX3 confers letrozole resistance via transactivation of FGFR1 signaling, and this requires interaction with the MTA1-HDAC2 complex. Patient-derived xenograft, pharmacological STAT3 inhibition, gain/loss-of-function, microarray profiling, co-immunoprecipitation (PBX3-MTA1-HDAC2 complex) Endocrine-related cancer Medium 33608482
2022 ATRAP directs USP14-mediated deubiquitination and stabilization of PBX3 protein, preventing its degradation. USF1 transcriptionally activates ATRAP expression, creating a USF1/ATRAP/PBX3 axis that activates AKT/mTOR signaling in breast cancer. Co-immunoprecipitation (ATRAP-PBX3, USP14-PBX3), ubiquitination assay, protein stability assay, microarray analysis, functional assays International journal of biological sciences Medium 35414770
2024 PHAX stabilizes PBX3 mRNA through interaction with LIN28B (RNA-binding protein). PBX3 then directly binds to the TET2 promoter and transcriptionally represses it, promoting esophageal cancer cell proliferation and suppressing apoptosis and autophagy. Co-immunoprecipitation (PHAX-LIN28B), mRNA stability assay, ChIP (PBX3 at TET2 promoter), luciferase reporter assay, KD/OE functional assays, mouse tumor model Cancer science Medium 39668567
2025 PBX3 directly binds a cis-regulatory element (SFE1) within intron 1 of SHH and represses its transcriptional activity in the chick Frontonasal Ectodermal Zone; this is opposite to PBX1, which activates transcription through the same element. Overexpressing PBX3 decreases SHH expression, while reducing PBX3 induces ectopic SHH expression. RCAS viral overexpression/knockdown in chick embryos, ChIP-seq (PBX3/PBX1 binding), ATAC-seq, luciferase reporter assay, in ovo electroporation of reporter constructs PLoS genetics High 40397886
2021 P2X7 receptor activation upregulates Pbx3 expression in MLL-rearranged AML cells, and the P2X7-Pbx3 pathway accounts for P2X7's pro-leukemic effects on cell proliferation and leukemia stem cell levels. shRNA knockdown, mouse AML model, patient-derived xenograft, P2X7 antagonist treatment, nude mouse xenograft Haematologica Medium 32165482
2022 P2X1 phosphorylation at S387 and T389 is required for its leukemia-promoting effects. ATP-P2X1-mediated signaling upregulates PBX3, which transactivates BCAT1 to maintain leukemia-initiating cell (LIC) fates. P2X1 deletion (mouse AML model), phospho-site mutagenesis, gene expression analysis, ChIP (PBX3 transactivation of BCAT1), P2X1 antagonist treatment Leukemia Medium 36418376
2025 Pbx3 suppresses type I interferon response genes during MLL-AF9-driven AML progression in vivo. Leukemia progression is associated with Pbx3 upregulation in progenitor cells and downregulation of IFN-response genes; enhancing IFN signaling (IFNα) induces leukemic cell differentiation, and this is partially overcome by Pbx3 activity. CRISPR-mediated chromosomal translocation (MLL-AF9 model), in vivo leukemia progression assay, IFNα treatment, gene expression analysis Cancer gene therapy Medium 40108441
2018 A human PBX3 variant (p.A136V), introduced into the homologous zebrafish pbx4 gene (p.A131V) via CRISPR-Cas9 precise genome editing, acts as a genetic modifier of cardiac morphogenesis: homozygous pbx4 p.A131V zebrafish are viable but the variant enhances the embryonic cardiac defect caused by loss of the Hand2 cardiac specification factor. CRISPR-Cas9 precision genome editing (single-stranded oligodeoxynucleotide knock-in), zebrafish genetic modifier assay (pbx4 p.A131V × hand2 loss-of-function) Disease models & mechanisms Medium 30355621
2014 PBX3 differential DNA methylation correlates with PBX3 gene expression in AML patients. In inv(16)/CBFB-MYH11 AML, targeted bisulfite sequencing revealed a hypomethylation pattern associated with genes upregulated in this subtype. Targeted bisulfite sequencing, 454 bisulfite pyrosequencing, microarray gene expression profiling (correlation of methylation with expression) Journal of hematology & oncology Low 25266220
2018 Inactivation of PBX3 and HOXA9 by reducing H3K79 methylation (via DOT1L inhibitor EPZ5676) promotes apoptosis in NPM1-mutated (NPMc+) leukemic cells. NPMc+ overexpression increases H3K79me2/me3 at the HOXA9 gene locus (but not the PBX3 locus); PBX3 expression is positively regulated by HOXA9; and reduction of either PBX3 or HOXA9 causes NPMc+ cell apoptosis. ChIP-seq (H3K79 methylation at HOXA9/PBX3 loci), siRNA knockdown, DOT1L inhibitor (EPZ5676) treatment, NPMc+ overexpression/depletion, apoptosis assay Theranostics Medium 30214626
2022 PBX3 acts as a transcriptional activator of the lncRNA DLG1-AS1 in triple-negative breast cancer (TNBC) cells, as demonstrated by ChIP assay showing PBX3 binding to the DLG1-AS1 promoter. ChIP (PBX3 at DLG1-AS1 promoter), luciferase reporter assay, functional TNBC cell assays Molecular therapy oncolytics Low 35592389
2025 METTL3 promotes m6A modification of PBX3 mRNA, leading to its upregulation. PBX3 in turn binds the CA9 promoter and activates its transcription, suppressing ferroptosis in esophageal squamous cell carcinoma. MeRIP assay (m6A on PBX3 mRNA), ChIP (PBX3 at CA9 promoter), luciferase reporter assay, ferroptosis assays (ROS, MDA, Fe2+), KD/OE functional assays, xenograft Pathology, research and practice Medium 40048803

Source papers

Stage 0 corpus · 94 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1991 PBX2 and PBX3, new homeobox genes with extensive homology to the human proto-oncogene PBX1. Molecular and cellular biology 272 1682799
2011 Let-7c functions as a metastasis suppressor by targeting MMP11 and PBX3 in colorectal cancer. The Journal of pathology 134 21984339
2012 PBX3 is an important cofactor of HOXA9 in leukemogenesis. Blood 118 23264595
2020 Circular RNA circCORO1C promotes laryngeal squamous cell carcinoma progression by modulating the let-7c-5p/PBX3 axis. Molecular cancer 106 32487167
2014 EWSR1-PBX3: a novel gene fusion in myoepithelial tumors. Genes, chromosomes & cancer 78 25231231
2004 Pbx3 deficiency results in central hypoventilation. The American journal of pathology 70 15466398
2015 PBX3 is targeted by multiple miRNAs and is essential for liver tumour-initiating cells. Nature communications 64 26420065
2015 Pbx3 and Meis1 cooperate through multiple mechanisms to support Hox-induced murine leukemia. Haematologica 63 25911551
2014 PBX3 promotes migration and invasion of colorectal cancer cells via activation of MAPK/ERK signaling pathway. World journal of gastroenterology 61 25561793
2011 Regulation of PBX3 expression by androgen and Let-7d in prostate cancer. Molecular cancer 60 21548940
2008 Expression of FOXP2 in the developing monkey forebrain: comparison with the expression of the genes FOXP1, PBX3, and MEIS2. The Journal of comparative neurology 59 18461604
2016 PBX3 and MEIS1 Cooperate in Hematopoietic Cells to Drive Acute Myeloid Leukemias Characterized by a Core Transcriptome of the MLL-Rearranged Disease. Cancer research 57 26747896
2017 MicroRNA-144-3p suppresses gastric cancer progression by inhibiting epithelial-to-mesenchymal transition through targeting PBX3. Biochemical and biophysical research communications 55 28111340
2012 MicroRNA profiling in pediatric pilocytic astrocytoma reveals biologically relevant targets, including PBX3, NFIB, and METAP2. Neuro-oncology 48 23161775
2022 EIF4A3-induced circTOLLIP promotes the progression of hepatocellular carcinoma via the miR-516a-5p/PBX3/EMT pathway. Journal of experimental & clinical cancer research : CR 46 35509064
2016 MicroRNA-33a-3p suppresses cell migration and invasion by directly targeting PBX3 in human hepatocellular carcinoma. Oncotarget 46 27285759
2018 PBX3 Is Part of an EMT Regulatory Network and Indicates Poor Outcome in Colorectal Cancer. Clinical cancer research : an official journal of the American Association for Cancer Research 45 29391352
2006 Spatio-temporal expression of Pbx3 during mouse organogenesis. Gene expression patterns : GEP 45 16434237
2004 Retinoic acid regulates the expression of PBX1, PBX2, and PBX3 in P19 cells both transcriptionally and post-translationally. Journal of cellular biochemistry 44 15095411
2013 PBX3 is overexpressed in gastric cancer and regulates cell proliferation. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 41 24375258
2020 PBX3 in Cancer. Cancers 40 32069812
2019 Cutaneous Syncytial Myoepithelioma Is Characterized by Recurrent EWSR1-PBX3 Fusions. The American journal of surgical pathology 40 31135487
2017 PBX3 is essential for leukemia stem cell maintenance in MLL-rearranged leukemia. International journal of cancer 37 28411381
2016 PBX3 is a putative biomarker of aggressive prostate cancer. International journal of cancer 36 27273830
2018 Inactivation of PBX3 and HOXA9 by down-regulating H3K79 methylation represses NPM1-mutated leukemic cell survival. Theranostics 35 30214626
2016 PBX3 promotes gastric cancer invasion and metastasis by inducing epithelial-mesenchymal transition. Oncology letters 35 27900025
2013 HOXA/PBX3 knockdown impairs growth and sensitizes cytogenetically normal acute myeloid leukemia cells to chemotherapy. Haematologica 35 23539541
2021 P2X7 promotes the progression of MLL-AF9 induced acute myeloid leukemia by upregulation of Pbx3. Haematologica 34 32165482
2018 PBX3/MEK/ERK1/2/LIN28/let-7b positive feedback loop enhances mesenchymal phenotype to promote glioblastoma migration and invasion. Journal of experimental & clinical cancer research : CR 34 30016974
2021 LncRNA H19 suppresses pyroptosis of cardiomyocytes to attenuate myocardial infarction in a PBX3/CYP1B1-dependent manner. Molecular and cellular biochemistry 32 33389498
2017 MiR-320 inhibits the growth of glioma cells through downregulating PBX3. Biological research 31 28934982
2001 Novel alternative PBX3 isoforms in leukemia cells with distinct interaction specificities. Genes, chromosomes & cancer 29 11579467
2020 LncRNA HOXA-AS2 promotes the progression of prostate cancer via targeting miR-509-3p/PBX3 axis. Bioscience reports 28 32519740
2020 Long non-coding RNA HNF1A-AS1 upregulates OTX1 to enhance angiogenesis in colon cancer via the binding of transcription factor PBX3. Experimental cell research 27 32325080
2019 miR-129-5p suppresses proliferation, migration, and induces apoptosis in pancreatic cancer cells by targeting PBX3. Acta biochimica et biophysica Sinica 27 31518383
2018 Functional testing of a human PBX3 variant in zebrafish reveals a potential modifier role in congenital heart defects. Disease models & mechanisms 26 30355621
2020 SNHG10/DDX54/PBX3 Feedback Loop Contributes to Gastric Cancer Cell Growth. Digestive diseases and sciences 25 32712782
2016 MicroRNA-497 suppresses cell proliferation and induces apoptosis through targeting PBX3 in human multiple myeloma. American journal of cancer research 24 28042507
2022 USF1-ATRAP-PBX3 Axis Promote Breast Cancer Glycolysis and Malignant Phenotype by Activating AKT/mTOR Signaling. International journal of biological sciences 23 35414770
2021 LncRNA CD27-AS1 promotes acute myeloid leukemia progression through the miR-224-5p/PBX3 signaling circuit. Cell death & disease 23 34006845
2019 miR-302a inhibits human HepG2 and SMMC-7721 cells proliferation and promotes apoptosis by targeting MAP3K2 and PBX3. Scientific reports 23 30765768
2007 Pbx3 is required for normal locomotion and dorsal horn development. Developmental biology 23 18155191
2021 The transcription factor PBX3 promotes tumor cell growth through transcriptional suppression of the tumor suppressor p53. Acta pharmacologica Sinica 22 33526870
2018 miR-495 inhibits proliferation, migration, and invasion and induces apoptosis via inhibiting PBX3 in melanoma cells. OncoTargets and therapy 22 29670366
2023 PBX3 promotes pentose phosphate pathway and colorectal cancer progression by enhancing G6PD expression. International journal of biological sciences 21 37781025
2015 Fusion of the genes EWSR1 and PBX3 in retroperitoneal leiomyoma with t(9;22)(q33;q12). PloS one 19 25875009
2022 CircNRIP1 Exerts Oncogenic Functions in Papillary Thyroid Carcinoma by Sponging miR-653-5p and Regulating PBX3 Expression. Journal of oncology 16 35646117
2020 Knockdown of lncRNA HCG11 suppresses cell progression in ovarian cancer by modulating miR-144-3p/PBX3. European review for medical and pharmacological sciences 16 33215418
2019 MicroRNA-320a suppresses tumor progression by targeting PBX3 in gastric cancer and is downregulated by DNA methylation. World journal of gastrointestinal oncology 16 31662823
2021 HOXA11-AS induces cisplatin resistance by modulating the microRNA-98/PBX3 axis in nasopharyngeal carcinoma. Oncology letters 15 33968209
2021 Circular RNA circHECTD1 prevents Diosbulbin-B-sensitivity via miR-137/PBX3 axis in gastric cancer. Cancer cell international 15 34001137
2020 MiR-4458/human antigen R (HuR) modulates PBX3 mRNA stability in melanoma tumorigenesis. Archives of dermatological research 15 32157373
2020 Downregulation of lncRNA-HEIH curbs esophageal squamous cell carcinoma progression by modulating miR-4458/PBX3. Thoracic cancer 14 32449803
2019 EWSR1-PBX3 gene fusion in cutaneous syncytial myoepithelioma. Journal of cutaneous pathology 14 30834570
1994 Genetic linkage analysis of the Ak1, Col5a1, Epb7.2, Fpgs, Grp78, Pbx3, and Notch1 genes in the region of mouse chromosome 2 homologous to human chromosome 9q. Genomics 14 8088777
2022 Long non-coding RNA DSCAM-AS1 promotes pancreatic cancer progression via regulating the miR-136-5p/PBX3 axis. Bioengineered 13 35142595
2020 PBX3 Promotes Tumor Growth and Angiogenesis via Activation of AT1R/VEGFR2 Pathway in Papillary Thyroid Carcinoma. BioMed research international 13 32047817
2019 EWSR1-PBX3 fused myoepithelioma arising in metatarsal bone: Case report and review of the literature. Pathology international 13 30605259
2022 P2X1 enhances leukemogenesis through PBX3-BCAT1 pathways. Leukemia 12 36418376
2020 MiR-320a inhibits malignant phenotype of melanoma cells via targeting PBX3. Journal of B.U.ON. : official journal of the Balkan Union of Oncology 12 33099955
2021 Leptin-elicited PBX3 confers letrozole resistance in breast cancer. Endocrine-related cancer 11 33608482
2014 CBFB-MYH11 hypomethylation signature and PBX3 differential methylation revealed by targeted bisulfite sequencing in patients with acute myeloid leukemia. Journal of hematology & oncology 11 25266220
2023 Circ-ATIC regulates esophageal squamous cell carcinoma growth and metastasis through miR-1294/PBX3 pathway. Heliyon 10 36699282
2020 MiR-144 inhibits colorectal cancer cell migration and invasion by regulating PBX3. European review for medical and pharmacological sciences 10 33015777
2022 PBX3-activated DLG1-AS1 can promote the proliferation, invasion, and migration of TNBC cells by sponging miR-16-5p. Molecular therapy oncolytics 9 35592389
2022 Circ_0003489 facilitates multiple myeloma progression by targeting miR-433-3p/PBX3 axis. Hematology (Amsterdam, Netherlands) 9 36004524
2023 An intraosseous myoepithelial carcinoma with a EWSR1::PBX3 fusion. Genes, chromosomes & cancer 8 37129228
2021 Circular RNA circ_0032962 promotes trophoblast cell progression as ceRNA to target PBX3 via sponging miR-326 in preeclampsia. Reproductive biology 8 34742151
2020 Long noncoding RNA NORAD promotes the progression of retinoblastoma by sponging miR-136-5p/PBX3 axis. European review for medical and pharmacological sciences 8 32096159
2024 Myoepithelial Tumors of Bone With EWSR1::PBX3 Fusion: A Spectrum From Benign to Malignant. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 7 38763423
2021 Long non‑coding RNA LINC00460 serves as a potential biomarker and oncogene via regulation of the miR‑320b/PBX3 axis in acute myeloid leukemia. Molecular medicine reports 7 33846790
2024 Low expression of miR-182 caused by DNA hypermethylation accelerates acute lymphocyte leukemia development by targeting PBX3 and BCL2: miR-182 promoter methylation is a predictive marker for hypomethylation agents + BCL2 inhibitor venetoclax. Clinical epigenetics 6 38528641
2023 ERN1 dependent impact of glucose and glutamine deprivations on PBX3, PBXIP1, PAX6, MEIS1, and MEIS2 genes expression in U87 glioma cells. Endocrine regulations 6 36753664
2020 Long noncoding RNA NORAD promotes the progression of retinoblastoma by sponging miR 136-5p/PBX3 axis. European review for medical and pharmacological sciences 6 32374004
2020 MiR-655-3p inhibits growth and invasiveness of trophoblasts via targeting PBX3 and thus deteriorates preeclampsia. European review for medical and pharmacological sciences 6 33155190
2014 The miR-302 cluster transcriptionally regulated by POUV, SOX and STAT5B controls the undifferentiated state through the post-transcriptional repression of PBX3 and E2F7 in early chick development. Molecular reproduction and development 6 25394196
2023 Exosomal circKIAA1797 Regulates Cell Progression and Glycolysis by Targeting miR-4429/PBX3 Pathway in Gastric Cancer. Biochemical genetics 5 37730964
2020 MG132 inhibits the expression of PBX3 through miRNAs by targeting Argonaute2 in hepatoma cells. Saudi journal of biological sciences 5 32714042
2024 PHAX enhanced LIN28B-mediated PBX3 mRNA stability to promote esophageal cancer development. Cancer science 4 39668567
2023 LncRNA LINC00885 promotes bladder cancer progression by targeting the miR-98-5p/PBX3 axis. Cellular and molecular biology (Noisy-le-Grand, France) 4 37300672
2022 circNBPF10/miR-224 Axis Regulates PBX3 to Promote the Malignant Progression of Lung Cancer. Journal of oncology 4 35342419
2025 PBX1 and PBX3 transcription factors regulate SHH expression in the Frontonasal Ectodermal Zone through complementary mechanisms. PLoS genetics 3 40397886
2025 PBX3-HMGCR Axis Promotes Hepatocellular Carcinoma Progression Through Enhancing De Novo Cholesterol Biosynthesis. International journal of molecular sciences 3 40508020
2022 A case of cutaneous syncytial myoepithelioma with extensive adipocytic metaplasia: Usefulness of EWSR1-PBX3 gene fusion analysis. Journal of cutaneous pathology 3 34854109
2022 Long noncoding RNA-LINC00478 promotes the progression of clear cell renal cell carcinoma through PBX3. Journal of biochemical and molecular toxicology 3 36086865
2025 METTL3 enhances esophageal squamous cell carcinoma progression by suppressing ferroptosis through the PBX3/CA9 cascade. Pathology, research and practice 2 40048803
2024 Mitochondrial ATP Synthesis and Proton Transport Synergistically Mitigate Oligodendrocyte Progenitor Cell Dysfunction Following Transient Middle Cerebral Artery Occlusion via the Pbx3/Dguok/Kif21b Signaling Pathway. International journal of medical sciences 1 39239553
2026 PBX3 regulates mast cell parthanatos via TOP2A mediated DNA damage in allergic rhinitis. iScience 0 42006311
2025 Pbx3-mediated suppression of type I interferon response contributes to leukemia progression driven by MLL-AF9. Cancer gene therapy 0 40108441
2025 LncRNA HCP5 promotes the progression of gastric cancer through the miR-526b/PBX3 axis. American journal of translational research 0 40821037
2025 Review Article: Decoding the Role of PBX3 in Cancer: Molecular Mechanisms and Therapeutic Strategies. Critical reviews in oncogenesis 0 41662636
2024 PBX1 and PBX3 transcription factors regulate SHH expression in the Frontonasal Ectodermal Zone through complementary mechanisms. bioRxiv : the preprint server for biology 0 38895322
2022 Correction to "MicroRNA-320a suppresses tumor progression by targeting PBX3 in gastric cancer and is downregulated by DNA methylation". World journal of gastrointestinal oncology 0 35949221
2021 MicroRNA-497 suppresses cell proliferation and induces apoptosis through targeting PBX3 in human multiple myeloma [Retraction]. American journal of cancer research 0 34522465

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