Affinage

PBX3

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

Length
434 aa
Mass
47.2 kDa
Annotated
2026-04-29
94 papers in source corpus 30 papers cited in narrative 30 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PBX3 is a TALE-class homeodomain transcription factor that heterodimerizes with HOX, MEIS, and other homeodomain partners to regulate target gene transcription in developmental patterning, hematopoiesis, and oncogenesis. PBX3 binds directly to the promoters of diverse target genes—including p53, G6PD, HMGCR, TOP2A, TET2, SHH, CYP1B1, and BCAT1—where it can function as either a transcriptional activator or repressor depending on context and cofactor composition (PMID:33526870, PMID:37781025, PMID:40397886, PMID:39668567). In MLL-rearranged AML, PBX3 is a critical cofactor of HOXA9 and stabilizes MEIS1 by protecting it from ubiquitin-proteasome degradation; PBX3/MEIS1 co-expression is sufficient to transform hematopoietic progenitors and sustain leukemia stem cell self-renewal, while PBX3 deletion prolongs survival and promotes leukemic cell apoptosis (PMID:23264595, PMID:25911551, PMID:26747896, PMID:28411381). In development, Pbx3 is required for medullary respiratory neuron function and dorsal horn neuronal specification, and a human PBX3 variant acts as a genetic modifier of congenital heart defects (PMID:15466398, PMID:18155191, PMID:30355621).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 1991 High

    Establishing that PBX3 encodes a homeodomain transcription factor with high homology to PBX1 and undergoes alternative splicing answered whether the PBX family extends beyond PBX1 and defined PBX3's structural identity.

    Evidence Molecular cloning, sequence analysis, and Northern blot of PBX3 cDNA

    PMID:1682799

    Open questions at the time
    • No DNA-binding specificity or cofactor interactions defined
    • No functional role or phenotype established
  2. 2001 Medium

    Discovery that alternative PBX3 isoforms (PBX3C/D) lose interaction with PREP1 and show weak MEIS binding revealed that splicing diversifies PBX3 cofactor partnerships and may be functionally relevant in leukemia.

    Evidence RT-PCR identification of novel splice forms, co-immunoprecipitation with PREP1 and MEIS proteins

    PMID:11579467

    Open questions at the time
    • Functional consequences of isoform-specific cofactor loss not tested in vivo
    • No genome-wide analysis of isoform-specific DNA binding
  3. 2004 High

    Pbx3 knockout mice dying from central respiratory failure, combined with demonstration of a Pbx3-Rnx DNA-binding complex, established PBX3 as essential for medullary respiratory circuit function and identified a non-HOX partner.

    Evidence Pbx3-null mouse phenotyping, in vitro transcription assay, co-immunoprecipitation of Pbx3-Rnx

    PMID:15466398

    Open questions at the time
    • Direct transcriptional targets in respiratory neurons not identified
    • Redundancy with Pbx1/2 in brainstem not fully resolved
  4. 2004 Medium

    Demonstration that PBX3 protein is stabilized by MEIS association and retinoic acid treatment, with reduced proteasome-dependent degradation, established post-translational control of PBX3 abundance.

    Evidence Protein half-life measurement, proteasome inhibition, and MEIS co-association in P19 cells

    PMID:15095411

    Open questions at the time
    • Specific E3 ligase targeting PBX3 not identified
    • Mechanism linking RA signaling to PBX3 stabilization not fully dissected
  5. 2007 High

    Conditional Pbx3 loss caudal to the hindbrain revealed its requirement for dorsal horn interneuron specification, extending PBX3's developmental role beyond the brainstem to spinal cord patterning.

    Evidence Conditional knockout mouse with immunofluorescence for laminar markers and behavioral analysis

    PMID:18155191

    Open questions at the time
    • Direct transcriptional targets in dorsal horn progenitors not identified
    • Redundancy with Pbx1 in spinal cord incompletely characterized
  6. 2012 High

    Identification of PBX3 as a critical HOXA9 cofactor in MLL-fusion leukemogenesis—where PBX3 depletion blocks transformation and HOXA9/PBX3 co-expression drives leukemia—established the oncogenic role of the HOX-PBX3 axis and therapeutic vulnerability to HOX-PBX-disrupting peptides.

    Evidence shRNA knockdown, retroviral coexpression, in vivo leukemia transplantation, HXR9 peptide inhibitor

    PMID:23264595

    Open questions at the time
    • Genome-wide targets of HOXA9-PBX3 complex in leukemia not mapped
    • HXR9 selectivity for PBX3 versus other PBX family members not established
  7. 2015 High

    Elucidation that PBX3 stabilizes MEIS1 by blocking its ubiquitination, and that trimeric HOXA9/MEIS1/PBX3 complexes require PBX3-MEIS1 dimerization, defined the biochemical mechanism by which PBX3 sustains the leukemogenic transcriptional program.

    Evidence Ubiquitination assay, proteasome inhibitor, EMSA for trimeric complex, colony formation and target gene qPCR

    PMID:25911551

    Open questions at the time
    • Identity of the E3 ligase targeting MEIS1 unknown
    • Structural basis of PBX3-MEIS1-HOXA9 ternary complex not resolved
  8. 2016 High

    PBX3/MEIS1 co-expression without ectopic HOX genes was sufficient to cause AML in vivo, demonstrating that PBX3-MEIS1 can upregulate endogenous Hoxa genes and drive transformation autonomously.

    Evidence Retroviral coexpression in murine HSPCs, in vivo AML transplantation, gene expression profiling

    PMID:26747896

    Open questions at the time
    • Mechanism of endogenous Hoxa gene upregulation by PBX3/MEIS1 not fully defined
    • Whether this applies to human HSPCs not tested
  9. 2015 High

    Demonstration that PBX3 drives tumor-initiating cell properties and a stemness transcriptional program (CACNA2D1, EpCAM, SOX2, NOTCH3) in hepatocellular carcinoma expanded PBX3's oncogenic role beyond leukemia to solid tumor stemness.

    Evidence shRNA and overexpression, TIC sorting, sphere formation, in vivo tumor initiation, miRNA regulation

    PMID:26420065

    Open questions at the time
    • Direct versus indirect regulation of stemness targets not fully resolved
    • Relevance across HCC molecular subtypes unknown
  10. 2014 Medium

    PBX3 was shown to activate MAPK/ERK signaling in colorectal cancer cells, promoting migration and invasion, revealing a signaling axis downstream of PBX3 in epithelial cancers.

    Evidence Overexpression/knockdown with wound healing, Boyden chamber, and p-ERK1/2 Western blot

    PMID:25561793

    Open questions at the time
    • Direct transcriptional target linking PBX3 to ERK activation not identified
    • Not confirmed in patient-derived models
  11. 2017 High

    CRISPR deletion of Pbx3 in MLL-AF9 AML mice extended survival and reduced LSC self-renewal, with aberrant histone marks (H3K79me2 up, H3K27me3 down) explaining high Pbx3 expression, linking epigenetic deregulation to PBX3-dependent leukemia maintenance.

    Evidence CRISPR/Cas9 Pbx3 deletion, leukemia transplant, ChIP-seq/qPCR for histone modifications

    PMID:28411381

    Open questions at the time
    • Whether DOT1L directly deposits H3K79me2 at Pbx3 locus not tested with inhibitor at this locus specifically
    • Mechanism connecting Pbx3 loss to LSC apoptosis not dissected
  12. 2018 Medium

    Discovery that PBX3 forms a positive feedback loop with LIN28/let-7b via MEK/ERK/c-Myc in glioblastoma, and that WNT/SNAIL/ZEB1 induce PBX3 through miR-200 repression in CRC, placed PBX3 within EMT-regulatory circuits controlled by miRNA networks.

    Evidence ChIP, dual-luciferase reporters, in vivo orthotopic model (GBM); KD/OE and transcriptomic analysis (CRC)

    PMID:29391352 PMID:30016974

    Open questions at the time
    • PBX3 direct transcriptional targets in EMT not comprehensively mapped
    • Feedback loop kinetics and stoichiometry not modeled
  13. 2018 High

    A human PBX3 variant (p.A136V) introduced into zebrafish pbx4 enhanced cardiac defects with Hand2 loss, establishing PBX3 as a genetic modifier of congenital heart disease through in vivo functional validation.

    Evidence CRISPR-Cas9 precision knock-in in zebrafish, genetic epistasis with Hand2 loss-of-function

    PMID:30355621

    Open questions at the time
    • Target genes mediating PBX3-Hand2 interaction in cardiac progenitors unknown
    • Human population frequency and penetrance of PBX3 cardiac variants not established
  14. 2021 Medium

    Multiple studies identified direct PBX3 transcriptional targets: PBX3 represses p53 to promote CRC proliferation, and upstream purinergic receptors P2X7/P2X1 regulate PBX3 levels to sustain leukemia stem cells via BCAT1 transactivation, broadening the catalogue of PBX3-regulated promoters and upstream regulators.

    Evidence ChIP and luciferase reporters at p53 promoter; P2X7/P2X1 knockout/antagonist with PBX3 knockdown epistasis in AML models

    PMID:32165482 PMID:33526870 PMID:36418376

    Open questions at the time
    • PBX3 cofactors at the p53 promoter not identified
    • Whether P2X-PBX3 axis operates in non-MLL AML subtypes unknown
  15. 2022 Medium

    Identification of ATRAP/USP14-mediated deubiquitination as a mechanism stabilizing PBX3 protein, and circTOLLIP/miR-516a-5p as an RNA axis elevating PBX3, revealed convergent post-translational and post-transcriptional mechanisms controlling PBX3 abundance in cancer.

    Evidence Co-IP and ubiquitination assay for USP14-PBX3; RNA pulldown, RIP, and luciferase reporters for circTOLLIP/miR-516a-5p/PBX3 axis

    PMID:35414770 PMID:35509064

    Open questions at the time
    • Whether USP14 is the sole deubiquitinase for PBX3 not tested
    • In vivo validation of USP14 inhibition reducing PBX3 levels incomplete
  16. 2023 Medium

    PBX3 was shown to directly activate G6PD transcription, stimulating the pentose phosphate pathway and NADPH production in CRC, establishing PBX3 as a regulator of cancer cell metabolic reprogramming.

    Evidence ChIP and luciferase reporter at G6PD promoter, PPP metabolite measurement, xenograft model

    PMID:37781025

    Open questions at the time
    • Whether PBX3 coordinates a broader metabolic gene program beyond G6PD not tested
    • Cofactors at G6PD promoter not identified
  17. 2025 High

    Demonstration that PBX3 represses SHH by binding a cis-regulatory element in its intron, activates HMGCR to enhance cholesterol biosynthesis, activates TOP2A to modulate allergic inflammation, and suppresses type I IFN response genes in AML expanded the functional repertoire to include both developmental gene repression and diverse disease-relevant transcriptional programs.

    Evidence ChIP-seq and ATAC-seq with functional reporters in chick embryo (SHH); ChIP/luciferase/xenograft (HMGCR); ChIP/KD mouse model (TOP2A); transcriptome analysis in CRISPR AML model (IFN genes)

    PMID:40108441 PMID:40397886 PMID:40508020 PMID:42006311

    Open questions at the time
    • Genome-wide map of PBX3 activating versus repressing sites not established in any single cell type
    • How PBX3 cofactor switching determines activation versus repression at different loci is mechanistically unresolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • The structural basis for PBX3's context-dependent switching between transcriptional activation and repression, the full spectrum of its direct genomic targets across cell types, and the therapeutic window for disrupting PBX3-dependent programs in AML and solid tumors remain unresolved.
  • No crystal or cryo-EM structure of PBX3 with any cofactor complex
  • No genome-wide ChIP-seq in human AML primary cells
  • Therapeutic index of PBX3 inhibition given developmental essentiality is unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 10 GO:0003677 DNA binding 8
Localization
GO:0005634 nucleus 4
Pathway
R-HSA-162582 Signal Transduction 5 R-HSA-1643685 Disease 5 R-HSA-1266738 Developmental Biology 4
Partners
DDX54HOXA9LIN28BMEIS1MTA1PREP1RNXUSP14
Complex memberships
HOXA9-PBX3-MEIS1 trimeric complexPBX3-MTA1-HDAC2 complexPBX3-Rnx complex

Evidence

Reading pass · 30 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1991 PBX3 encodes a homeodomain-containing transcription factor with 94% identity to PBX1 over 266 amino acids flanking the homeodomain; PBX3 mRNA is alternatively spliced to yield two translation products with different carboxy termini, analogous to PBX1 splicing. Molecular cloning, sequence analysis, Northern blot with alternative splicing characterization Molecular and cellular biology High 1682799
2001 Novel PBX3 isoforms (PBX3C and PBX3D) generated by alternative splicing cannot interact with the PBX-interacting factor PREP1 and show only weak interaction with MEIS proteins, unlike canonical PBX3A/B isoforms; PBX3C expression is favored in leukemia cells whereas PBX3D is favored in normal cells. RT-PCR identification of novel splice forms, co-immunoprecipitation/interaction assays with PREP1 and MEIS proteins Genes, chromosomes & cancer Medium 11579467
2004 Pbx3-deficient mice die within hours of birth from central respiratory failure due to abnormal inspiratory neuron activity in the medulla; Pbx3 forms a DNA-binding complex with the metaHox transcription factor Rnx, and Rnx-mediated transcriptional enhancement in vitro is compromised in the absence of Pbx3. Knockout mouse model (respiratory phenotype readout), in vitro transcription assay, co-immunoprecipitation of Pbx3-Rnx complex The American journal of pathology High 15466398
2004 PBX1, PBX2, and PBX3 proteins are stabilized post-translationally by retinoic acid treatment in P19 cells; protein half-lives are extended, partly through RA-dependent association with increased levels of MEIS proteins and possibly through reduced proteasome-dependent degradation. Protein half-life measurement, RA treatment, proteasome inhibition, co-association with MEIS proteins in P19 cells Journal of cellular biochemistry Medium 15095411
2007 Conditional loss of Pbx3 function in tissues caudal to the hindbrain causes dorsal horn defects including reduced calbindin-, PKC-γ-, and calretinin-expressing neurons in laminae I–III, misspecification of glutamatergic neurons, and deficits in locomotion and sensation. Conditional knockout mouse, immunofluorescence for neuronal markers, behavioral analysis Developmental biology High 18155191
2012 PBX3 acts as a critical cofactor of HOXA9 in leukemogenesis: shRNA-mediated depletion of Pbx3 inhibits MLL-fusion-mediated cell transformation; coexpressed PBX3 synergizes with HOXA9 to promote transformation in vitro and leukemia in vivo; the small peptide HXR9 disrupts HOX-PBX interactions and selectively kills leukemic cells overexpressing HOXA/PBX3. shRNA knockdown, retroviral coexpression, in vivo leukemia transplantation model, peptide inhibitor (HXR9) Blood High 23264595
2014 PBX3 promotes colorectal cancer cell migration and invasion by activating the MAPK/ERK signaling pathway, as evidenced by upregulation of phosphorylated ERK1/2 upon PBX3 overexpression and suppression of migration/invasion upon PBX3 knockdown. Plasmid overexpression and shRNA knockdown, wound healing and Boyden chamber assays, Western blot for p-ERK1/2 World journal of gastroenterology Medium 25561793
2015 Pbx3 dimerizes with Meis1 to support Hox-induced leukemia: Pbx3 binding prevents ubiquitination and proteasomal degradation of Meis1 (stabilization dependent on the Pbx-binding domain of Meis1); Pbx3 also transcriptionally induces endogenous Meis1; disruption of Meis1/Pbx3 dimerization abolishes high-affinity Hoxa9/Meis1/Pbx3 DNA complexes in vitro and impairs colony formation and expression of Meis1 target genes Flt3 and Trib2. Deletion analysis of Meis1 domains, ubiquitination assay, proteasome inhibitor treatment, electrophoretic mobility shift assay (EMSA), colony formation, qPCR of target genes Haematologica High 25911551
2015 PBX3 is sufficient and necessary for acquisition and maintenance of hepatocellular carcinoma tumor-initiating cell (TIC) properties; PBX3 drives a transcriptional programme activating CACNA2D1, EpCAM, SOX2, and NOTCH3; it is synergistically targeted by let-7c, miR-200b, miR-222, and miR-424. shRNA knockdown and overexpression, α2δ1+ TIC sorting, sphere formation assay, luciferase reporter assays, in vivo tumor initiation Nature communications High 26420065
2016 PBX3 and MEIS1 co-expression, without ectopic HOX gene expression, is sufficient to transform normal mouse hematopoietic stem/progenitor cells and cause AML in vivo; PBX3/MEIS1 interaction is required, as disruption of their binding diminishes transformation and upregulation of endogenous Hoxa genes. Retroviral coexpression in murine HSPCs, in vivo AML transplantation, gene expression profiling, binding disruption experiments Cancer research High 26747896
2017 Pbx3 deletion using CRISPR/Cas9 in MLL-AF9-induced AML mouse models significantly prolongs survival and decreases leukemia burden by reducing leukemia stem cell (LSC) self-renewal and promoting LSC apoptosis; aberrant epigenetic modifications (increased H3K79me2, decreased H3K9me3 and H3K27me3) in LSCs account for high Pbx3 expression. CRISPR/Cas9 Pbx3 deletion, leukemia transplantation model, ChIP-seq/qPCR for histone modifications, LSC functional assays International journal of cancer High 28411381
2018 PBX3 mediates glioblastoma mesenchymal transition through activation of MEK/ERK1/2, leading to c-Myc-driven LIN28 upregulation, which inhibits let-7b biogenesis; let-7b in turn suppresses PBX3 by targeting its 3'-UTR, forming a positive feedback loop; ChIP assays confirmed PBX3 involvement in this regulatory cascade. Western blot, qRT-PCR, dual-luciferase reporter, ChIP, rescue experiments, orthotopic mouse model Journal of experimental & clinical cancer research Medium 30016974
2018 PBX3 expression in colorectal cancer is induced by WNT pathway activation and by EMT transcription factors SNAIL and ZEB1 through indirect mechanisms mediated by microRNA miR-200; PBX3 is required for a full EMT phenotype in colon cancer cells. Reporter assay, cell biology KD/OE, transcriptomic analysis, in situ analysis Clinical cancer research Medium 29391352
2018 PBX3 promotes NPM1-mutated leukemic cell survival; HOXA9 positively regulates PBX3 expression; hypermethylated H3K79 (via DOT1L) is present at the expressed HOXA9 gene but not PBX3; DOT1L inhibitor EPZ5676 reduces HOXA9 and PBX3 expression causing apoptosis in NPMc+ cells. ChIP-seq, shRNA knockdown, NPMc+ overexpression/depletion, DOT1L inhibitor treatment, apoptosis assay Theranostics High 30214626
2021 PBX3 binds to the p53 promoter and suppresses its transcriptional activity, thereby downregulating p21 expression and promoting colorectal cancer cell proliferation; PBX3 regulates tumor growth through the p53/p21 axis. ChIP assay, luciferase reporter assay, shRNA knockdown, proliferation and apoptosis assays Acta pharmacologica Sinica Medium 33526870
2021 Leptin activates PBX3 expression in a STAT3-dependent manner; PBX3 confers letrozole resistance in breast cancer by transactivating FGFR1 signaling through interaction with the MTA1-HDAC2 complex. Patient-derived xenograft model, pharmacological STAT3 inhibition, co-immunoprecipitation of PBX3/MTA1-HDAC2, loss- and gain-of-function experiments, gene expression profiling Endocrine-related cancer Medium 33608482
2021 P2X7 receptor promotes MLL-rearranged AML progression through upregulation of Pbx3, which mediates P2X7's pro-leukemic effects on cell proliferation and leukemia stem cell levels. Mouse AML model, nude mouse xenograft, patient-derived xenograft, shRNA/overexpression, P2X7 antagonist Haematologica Medium 32165482
2021 P2X1 phosphorylation at S387 and T389 is essential for its leukemia-promoting effects; ATP-P2X1 signaling upregulates PBX3 to transactivate BCAT1, maintaining leukemia-initiating cell fates in AML. P2X1 deletion, phosphorylation site mutagenesis, murine AML model, PBX3 knockdown, BCAT1 expression analysis Leukemia Medium 36418376
2021 lncRNA H19 inhibits CYP1B1 expression by regulating PBX3, which binds CYP1B1 promoters to suppress their activity, thereby attenuating NLRP3-dependent pyroptosis of cardiomyocytes. RIP assay, dual-luciferase reporter assay, H19 and CYP1B1 overexpression/knockdown in hypoxic cardiomyocytes and MI rat model Molecular and cellular biochemistry Medium 33389498
2022 ATRAP promotes USP14-mediated deubiquitination and stabilization of PBX3; USF1 directly targets ATRAP; the USF1/ATRAP/PBX3 axis activates AKT/mTOR signaling to promote breast cancer glycolysis and malignant phenotype. Microarray analysis, co-immunoprecipitation, ubiquitination assay, AKT/mTOR pathway assessment, functional cell assays International journal of biological sciences Medium 35414770
2023 PBX3 directly binds to the G6PD promoter and promotes its transcriptional activity, leading to pentose phosphate pathway stimulation, increased NADPH and nucleotide production, decreased ROS, and enhanced colorectal cancer tumor growth in vitro and in vivo. ChIP assay, luciferase reporter assay, PBX3 knockdown/overexpression, PPP metabolite measurement, xenograft model International journal of biological sciences Medium 37781025
2024 PHAX interacts with LIN28B and enhances LIN28B-mediated stabilization of PBX3 mRNA; PBX3 directly binds to the TET2 promoter region and inhibits its transcription, thereby promoting esophageal cancer cell proliferation and suppressing apoptosis and autophagy. Co-immunoprecipitation (PHAX-LIN28B), mRNA stability assay, ChIP assay (PBX3 at TET2 promoter), knockdown/overexpression, xenograft model Cancer science Medium 39668567
2025 PBX3 directly binds to the -167/-151 region of the HMGCR promoter and increases its transcriptional activity, enhancing cholesterol biosynthesis in hepatocellular carcinoma cells and promoting tumorigenic potential in vivo. ChIP assay, luciferase reporter assay, PBX3 knockdown/overexpression, cholesterol measurement, xenograft model International journal of molecular sciences Medium 40508020
2025 PBX3 directly binds to the TOP2A promoter to activate its transcription; PBX3 knockdown reduces TOP2A expression and significantly alleviates allergic rhinitis symptoms (reduced sneezing, nasal discharge, inflammatory cell infiltration) in mice. ChIP assay, mast cell culture, PBX3 knockdown mouse model, histological analysis of nasal tissue iScience Medium 42006311
2025 In the chick frontonasal ectodermal zone, PBX3 and PBX1 bind a cis-regulatory element (SFE1) within intron 1 of SHH; PBX1 binding activates SHH transcription while PBX3 binding represses it; overexpression of PBX3 decreases SHH expression and reducing PBX3 induces ectopic SHH expression. RCAS viral overexpression/knockdown in chick embryos, ChIP-seq, ATAC-seq, in ovo electroporation reporter assay, in vitro luciferase reporter assay PLoS genetics High 40397886
2025 Pbx3-mediated suppression of type I interferon response genes is required for AML progression driven by MLL-AF9; Pbx3 upregulation in progenitor cells during leukemia progression correlates with downregulation of interferon response genes, and IFN-α administration induces leukemic cell differentiation. CRISPR-mediated MLL-AF9 murine AML model, transcriptome analysis, IFN-α treatment, gene expression in progenitor compartments Cancer gene therapy Medium 40108441
2020 SNHG10 lncRNA maintains PBX3 mRNA stability through recruiting the RNA helicase DDX54 (which binds both SNHG10 and PBX3 mRNA); PBX3 protein in turn binds the SNHG10 promoter and activates its transcription, forming a positive feedback loop that promotes gastric cancer cell growth. ChIP assay (PBX3 at SNHG10 promoter), RIP and RNA pull-down (DDX54-SNHG10-PBX3), luciferase reporter, mRNA stability assay, rescue experiments Digestive diseases and sciences Medium 32712782
2022 EIF4A3 promotes the biogenesis of circTOLLIP without affecting its stability; circTOLLIP sponges miR-516a-5p to elevate PBX3 expression, which activates the EMT pathway in hepatocellular carcinoma. MS2-RNA pulldown, biotin-labeled RNA pulldown, RIP, luciferase reporter, FISH, RNA sequencing, gain/loss-of-function assays in vitro and in vivo Journal of experimental & clinical cancer research Medium 35509064
2016 PBX3 promotes gastric cancer invasion and metastasis by inducing EMT (increasing N-cadherin and vimentin, reducing E-cadherin) and activating the AKT signaling pathway; PBX3 overexpression also increases MMP-9 activity. Western blot for EMT markers and p-AKT, gelatin zymography for MMP-9, Transwell assay, nude mouse peritoneal metastasis model Oncology letters Medium 27900025
2018 A human PBX3 variant (p.A136V) introduced into the homologous zebrafish pbx4 gene enhances cardiac morphogenesis defects caused by loss of Hand2, demonstrating that PBX3 acts as a genetic modifier of congenital heart defects. CRISPR-Cas9 precision genome editing with single-stranded oligodeoxynucleotide to introduce p.A131V in zebrafish pbx4; double mutant analysis with Hand2 loss-of-function Disease models & mechanisms High 30355621

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 133 21984339
2012 PBX3 is an important cofactor of HOXA9 in leukemogenesis. Blood 116 23264595
2020 Circular RNA circCORO1C promotes laryngeal squamous cell carcinoma progression by modulating the let-7c-5p/PBX3 axis. Molecular cancer 105 32487167
2014 EWSR1-PBX3: a novel gene fusion in myoepithelial tumors. Genes, chromosomes & cancer 77 25231231
2004 Pbx3 deficiency results in central hypoventilation. The American journal of pathology 69 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 61 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 56 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
2016 MicroRNA-33a-3p suppresses cell migration and invasion by directly targeting PBX3 in human hepatocellular carcinoma. Oncotarget 46 27285759
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 45 35509064
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
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 43 29391352
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 39 32069812
2019 Cutaneous Syncytial Myoepithelioma Is Characterized by Recurrent EWSR1-PBX3 Fusions. The American journal of surgical pathology 39 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
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
2018 Inactivation of PBX3 and HOXA9 by down-regulating H3K79 methylation represses NPM1-mutated leukemic cell survival. Theranostics 33 30214626
2021 LncRNA H19 suppresses pyroptosis of cardiomyocytes to attenuate myocardial infarction in a PBX3/CYP1B1-dependent manner. Molecular and cellular biochemistry 31 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
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
2022 USF1-ATRAP-PBX3 Axis Promote Breast Cancer Glycolysis and Malignant Phenotype by Activating AKT/mTOR Signaling. International journal of biological sciences 22 35414770
2021 LncRNA CD27-AS1 promotes acute myeloid leukemia progression through the miR-224-5p/PBX3 signaling circuit. Cell death & disease 22 34006845
2018 miR-495 inhibits proliferation, migration, and invasion and induces apoptosis via inhibiting PBX3 in melanoma cells. OncoTargets and therapy 22 29670366
2021 The transcription factor PBX3 promotes tumor cell growth through transcriptional suppression of the tumor suppressor p53. Acta pharmacologica Sinica 21 33526870
2023 PBX3 promotes pentose phosphate pathway and colorectal cancer progression by enhancing G6PD expression. International journal of biological sciences 20 37781025
2015 Fusion of the genes EWSR1 and PBX3 in retroperitoneal leiomyoma with t(9;22)(q33;q12). PloS one 19 25875009
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
2022 CircNRIP1 Exerts Oncogenic Functions in Papillary Thyroid Carcinoma by Sponging miR-653-5p and Regulating PBX3 Expression. Journal of oncology 15 35646117
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
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 PBX3 Promotes Tumor Growth and Angiogenesis via Activation of AT1R/VEGFR2 Pathway in Papillary Thyroid Carcinoma. BioMed research international 12 32047817
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
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
2021 Circular RNA circ_0032962 promotes trophoblast cell progression as ceRNA to target PBX3 via sponging miR-326 in preeclampsia. Reproductive biology 7 34742151
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
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 PBX3-HMGCR Axis Promotes Hepatocellular Carcinoma Progression Through Enhancing De Novo Cholesterol Biosynthesis. International journal of molecular sciences 3 40508020
2024 PHAX enhanced LIN28B-mediated PBX3 mRNA stability to promote esophageal cancer development. Cancer science 3 39668567
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 PBX1 and PBX3 transcription factors regulate SHH expression in the Frontonasal Ectodermal Zone through complementary mechanisms. PLoS genetics 2 40397886
2025 METTL3 enhances esophageal squamous cell carcinoma progression by suppressing ferroptosis through the PBX3/CA9 cascade. Pathology, research and practice 1 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