Affinage

HOXA5

Homeobox protein Hox-A5 · UniProt P20719

Length
270 aa
Mass
29.3 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

HOXA5 is a homeodomain transcription factor that specifies regional identity along the anteroposterior axis and orchestrates mesenchymal-epithelial signaling in multiple organs during development and tissue homeostasis. It binds ATTA-containing DNA motifs through its homeodomain and engages the co-factor Pbx1 via its YPWM motif; it directly transactivates the promoters of p53, progesterone receptor, pleiotrophin, hMLH1, Fabp4, and PPARγ while repressing JAG1 (thereby restraining Notch signaling) and Slug (via DNMT3A-mediated promoter methylation), linking it to apoptosis through caspases 2 and 8, Wnt pathway inhibition, and suppression of epithelial-mesenchymal transition (PMID:2565857, PMID:8635464, PMID:10879542, PMID:10875927, PMID:15757903, PMID:36536414, PMID:38521405, PMID:14701762, PMID:26678341). Its expression is induced by RAR-β-bound retinoic acid response elements, stabilized post-transcriptionally by HuR, and repressed by miR-130a, JARID1B-mediated H3K4 demethylation, and HOTAIR/DNMT3b-directed promoter methylation (PMID:17804711, PMID:23528537, PMID:17957028, PMID:26023081, PMID:31168296). In vivo, Hoxa5 loss causes cervicothoracic homeotic transformations, perinatal lethality with athymia and cardiac defects, lung alveogenesis failure with goblet cell metaplasia, defective gastric epithelial specification, and accelerated mammary lobuloalveolar development — phenotypes arising from its mesenchymal function — while gain-of-function diverts hematopoietic progenitors from erythroid to myeloid fate and eliminates intestinal cancer stem cells (PMID:1673020, PMID:7901120, PMID:17003488, PMID:12163410, PMID:16607641, PMID:10397719, PMID:26678341).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 1989 High

    Establishing that HOXA5 is a sequence-specific DNA-binding transcription factor resolved the basic molecular activity of this homeodomain protein, showing the core ATTA motif is essential for binding.

    Evidence DNase I footprinting and EMSA with mutagenesis of synthetic oligonucleotides in vitro

    PMID:2565857

    Open questions at the time
    • No endogenous target genes identified at this stage
    • No information on cofactor requirements for DNA binding
  2. 1993 High

    Mouse knockouts revealed that Hoxa5 is required for pharyngeal arch-derived organ development (thymus, parathyroid, thyroid) and specifies cervicothoracic (C3–T2) axial identity, establishing its in vivo developmental necessity and regional specificity.

    Evidence Hoxa5-null mice generated by gene targeting; skeletal and organ phenotyping

    PMID:1673020 PMID:7901120

    Open questions at the time
    • Cell-autonomous versus non-cell-autonomous mechanisms unresolved
    • Downstream target genes unknown
  3. 1993 High

    Cross-species functional equivalence with Drosophila Sex combs reduced demonstrated conservation of the Hox regulatory hierarchy and HOXA5's ability to activate downstream target genes such as fork head.

    Evidence Ectopic expression of mouse Hoxa5 in transgenic Drosophila with phenotypic and target gene analysis

    PMID:8095481

    Open questions at the time
    • Mammalian target genes not yet identified
    • Mechanism of target specificity unclear
  4. 1996 High

    Domain dissection showed that the homeodomain mediates nuclear targeting and function, while the YPWM motif confers biological specificity through physical interaction with co-factor Pbx1, establishing the structural basis of HOXA5 activity.

    Evidence Truncation mutagenesis with transactivation assays and in vitro Pbx1 interaction in cultured cells and transgenic Drosophila

    PMID:8635464

    Open questions at the time
    • No crystal structure of the HOXA5-Pbx1 complex
    • Other cofactors not explored
  5. 2000 High

    Identification of p53 and progesterone receptor as direct transcriptional targets connected HOXA5 to tumor suppression and hormone signaling, revealing it as a transactivator of clinically relevant promoters in breast cancer.

    Evidence Promoter-reporter assays, direct DNA binding by gel-shift, p53-dependent apoptosis assays, bisulfite methylation in primary tumors

    PMID:10875927 PMID:10879542

    Open questions at the time
    • Whether HOXA5 binds p53 promoter in vivo (ChIP) not yet shown at this time
    • Mechanism of promoter methylation-mediated HOXA5 silencing not elucidated
  6. 2002 High

    Organ-specific knockout studies in stomach, thyroid, and skeleton demonstrated that Hoxa5 functions non-cell-autonomously through mesenchymal-epithelial signaling, controlling Shh/Ihh/FGF10/TGF-β expression in mesenchyme to specify epithelial fates.

    Evidence Hoxa5-null mouse phenotyping with molecular marker in situ hybridization in stomach, thyroid, and skeleton; compound Hoxa5;Pax1 mutant epistasis

    PMID:11900462 PMID:12163410 PMID:12815622

    Open questions at the time
    • Direct transcriptional targets in mesenchyme not identified
    • Whether Hoxa5 binds Shh or FGF10 regulatory regions unknown
  7. 2004 High

    HOXA5-induced apoptosis was shown to operate through caspases 2 and 8 and to involve physical interaction with the anti-apoptotic protein Twist, providing a mechanistic basis for its p53-dependent and p53-independent pro-apoptotic functions.

    Evidence Caspase inhibitor panel and siRNA in inducible HOXA5-expressing breast cancer cells; reciprocal co-immunoprecipitation of HOXA5 and Twist

    PMID:14701762 PMID:15545268

    Open questions at the time
    • How HOXA5 activates caspase 2/8 transcriptionally or indirectly is unclear
    • Structural basis of HOXA5-Twist interaction unknown
  8. 2005 High

    ChIP-confirmed direct binding of HOXA5 to the pleiotrophin promoter, and identification of Cdx4-mediated posterior boundary repression of the Hoxa5 locus, revealed both a direct target gene and the upstream transcriptional logic that restricts Hoxa5 expression along the body axis.

    Evidence ChIP and EMSA for pleiotrophin promoter binding; Cdx-binding site mutagenesis in transgenic mouse reporters

    PMID:15684390 PMID:15757903

    Open questions at the time
    • Genome-wide map of direct HOXA5 targets not yet available
    • Whether Cdx proteins physically interact with HOXA5 protein unknown
  9. 2006 High

    In vivo studies established that Hoxa5 functions in lung and mammary mesenchyme to control alveolar myofibroblast positioning and lobulo-alveolar development, while hMLH1 was confirmed as a direct target linking HOXA5 to mismatch repair.

    Evidence Hoxa5-null lung histopathology; reciprocal mammary gland transplantation; ChIP at hMLH1 promoter with functional repair assay

    PMID:16607641 PMID:16756717 PMID:17003488

    Open questions at the time
    • Stromal signals downstream of Hoxa5 in mammary gland unidentified
    • Genome-wide mismatch repair consequences not assessed
  10. 2007 High

    A RAR-β→HOXA5 regulatory axis was established: RAR-β directly binds a RARE in the HOXA5 3' region, and miR-130a was identified as a direct post-transcriptional repressor of HOXA5, together defining the retinoic acid-responsive circuit controlling HOXA5 expression.

    Evidence ChIP for RAR-β at HOXA5 RARE; luciferase reporter for miR-130a binding to HOXA5 3'-UTR; siRNA knockdown of RAR-β

    PMID:17804711 PMID:17957028

    Open questions at the time
    • Other RARs that may regulate HOXA5 not tested
    • Quantitative contribution of miR-130a vs. promoter methylation to HOXA5 silencing unknown
  11. 2013 High

    Post-transcriptional regulation of HOXA5 was further elaborated: HuR stabilizes HOXA5 mRNA upon RA treatment, while c-Myc-driven miR-130a basally represses HOXA5 translation, establishing a dual-layer (miRNA + RBP) control module.

    Evidence RNA-binding protein pulldown, miRNA inhibition/overexpression, mRNA stability assays in breast cancer cells

    PMID:23528537

    Open questions at the time
    • Whether HuR binds HOXA5 mRNA in non-cancer contexts not tested
    • Additional miRNAs targeting HOXA5 not systematically profiled at this time
  12. 2015 High

    HOXA5 was placed as an antagonist of Wnt signaling and intestinal stem cell fate, and its promoter was shown to be repressed by JARID1B through H3K4 demethylation, establishing both a pathway-level tumor-suppressive mechanism and an epigenetic silencing axis.

    Evidence In vivo gain/loss-of-function in mouse intestine with Wnt reporters and cancer stem cell assays; ChIP for H3K4me at HOXA5 promoter in endothelial-specific Jarid1b knockout mice

    PMID:26023081 PMID:26678341

    Open questions at the time
    • Direct Wnt target genes repressed by HOXA5 not identified
    • Whether JARID1B regulation of HOXA5 operates in non-endothelial tissues unclear
  13. 2017 High

    Physical association of HOXA5 with STAT3, shown by co-immunoprecipitation, revealed cooperative transactivation of PD-L1, linking HOXA5 to immune checkpoint regulation in melanoma.

    Evidence Co-IP of HOXA5 and STAT3, PD-L1 promoter-reporter assay, siRNA knockdown, T-cell killing assay

    PMID:29174371

    Open questions at the time
    • Whether HOXA5-STAT3 interaction is direct or bridged by DNA unknown
    • Generalizability beyond melanoma not tested
  14. 2019 Medium

    HOTAIR/DNMT3b-mediated DNA methylation was shown to silence the HOXA5 promoter in AML, and HOXA5's transcriptional activation of PPARγ was linked to anti-inflammatory macrophage polarization, broadening its epigenetic regulation and immune-metabolic roles.

    Evidence ChIP and methylation assays for DNMT3b at HOXA5 promoter; Hoxa5 overexpression in adipocytes with transcriptome sequencing and macrophage polarization assays

    PMID:31168296 PMID:31441588

    Open questions at the time
    • Direct HOXA5 binding to PPARγ promoter not demonstrated
    • HOTAIR-DNMT3b mechanism based on single lab without reconstitution
  15. 2021 High

    HINT1 was shown to suppress HOXA5 transcription via PKCβ1/MEK/ERK/YY1 signaling in cardiomyocytes, and ChIP confirmed direct HOXA5 binding to the p53 promoter ATTA motif in fibroblasts, extending HOXA5 function to cardiac hypertrophy and fibrotic disease.

    Evidence Co-IP of HINT1-PKCβ1, AAV9-mediated cardiac-specific overexpression/knockdown with transverse aortic constriction; ChIP PCR at p53 promoter in hypertrophic scar fibroblasts

    PMID:33414417 PMID:34098726

    Open questions at the time
    • Whether YY1 directly binds the HOXA5 promoter not demonstrated
    • Cardiac-specific HOXA5 targets beyond TGF-β pathway unknown
  16. 2022 High

    HOXA5 was shown to recruit DNMT3A to the Slug promoter, increasing its methylation and silencing EMT, establishing a direct epigenetic effector mechanism for HOXA5 in tumor suppression.

    Evidence ChIP and methylated DNA immunoprecipitation at Slug promoter in renal cell carcinoma cells

    PMID:36536414

    Open questions at the time
    • Whether HOXA5-DNMT3A interaction is direct or mediated through intermediates not shown
    • Genome-wide scope of HOXA5-directed DNA methylation unknown
  17. 2024 High

    Conditional knockout and knockin of Hoxa5 in kidney proximal tubules demonstrated that HOXA5 directly represses JAG1 transcription, restraining Notch signaling to prevent kidney fibrosis, providing the first tissue-specific conditional genetic evidence for HOXA5 in renal pathology.

    Evidence ChIP at JAG1 promoter, conditional Hoxa5 KO/KI in kidney, genome-wide methylation analysis, 5-Aza rescue

    PMID:38521405

    Open questions at the time
    • Whether HOXA5 represses other Notch ligands in kidney not tested
    • Upstream signals leading to HOXA5 promoter hypermethylation in fibrotic kidney undefined

Open questions

Synthesis pass · forward-looking unresolved questions
  • A genome-wide map of direct HOXA5 binding sites (by ChIP-seq in primary tissues), the structural basis of its interactions with Pbx1, Twist, STAT3, and DNMT3A, and the relative contributions of transcriptional versus epigenetic effector mechanisms across tissue contexts remain unresolved.
  • No published ChIP-seq in primary developmental tissues
  • No crystal or cryo-EM structure of HOXA5 with any partner
  • Quantitative contribution of HOXA5 to Wnt vs. Notch vs. p53 pathways in different tissue contexts unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 8 GO:0003677 DNA binding 5
Localization
GO:0005634 nucleus 2
Pathway
R-HSA-1266738 Developmental Biology 9 R-HSA-74160 Gene expression (Transcription) 8 R-HSA-162582 Signal Transduction 4 R-HSA-1643685 Disease 3 R-HSA-4839726 Chromatin organization 3 R-HSA-5357801 Programmed Cell Death 3 R-HSA-168256 Immune System 1
Partners
DNMT3AELAVL1FKHRFOXA2PBX1STAT3TWIST1

Evidence

Reading pass · 41 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1989 HOXA5 (Hox-1.3) protein is a nuclear phosphoprotein that binds specific DNA sequences via its homeodomain; DNase I footprinting identified a binding site 144 bp upstream of the Hox-1.3 transcription start, and the consensus binding motif CPyPyNATTAT/GPy was deduced; base substitutions in the core ATTA sequence abolished binding. DNase I footprinting, electrophoretic mobility shift assay (EMSA), in vitro DNA binding with synthetic oligonucleotides, subcellular fractionation Genes & development High 2565857
1991 Targeted disruption of Hoxa5 (Hox-1.5) in mice causes perinatal lethality with athymia, aparathyroidism, reduced thyroid and submaxillary tissue, heart/artery defects, and craniofacial abnormalities, establishing Hoxa5 as required for pharyngeal arch and neural crest-derived organ development. Gene targeting in embryonic stem cells, mouse knockout Nature High 1673020
1993 Loss of Hoxa5 function in mice causes homeotic transformations restricted to cervical vertebra C3 through thoracic vertebra T2, demonstrating Hoxa5 specifies regional axial identity in the cervicothoracic skeleton; the most frequent anomaly is posterior transformation of C7 into a rib-bearing thoracic vertebra. Targeted mutagenesis in embryonic stem cells, skeletal analysis of Hoxa5-/- mice Genes & development High 7901120
1993 Mouse Hox-a5 is functionally equivalent to Drosophila Sex combs reduced (Scr): ectopic expression of Hox-a5 in Drosophila induces Scr-like homeotic transformations and activates the Scr target gene fork head, demonstrating direct participation in a regulatory hierarchy. Transgenic Drosophila overexpression, phenotypic analysis, target gene (fork head) expression assay Genes & development High 8095481
1996 Functional dissection of Hox-a5 showed: (1) the homeodomain is essential for nuclear targeting and protein function; (2) the N-terminal region contributes to transcriptional activation and transformation potential but not functional specificity; (3) the YPWM motif is essential for biological specificity and mediates interaction with co-factor Pbx1 in vitro. Truncation mutagenesis, transactivation assays in cultured cells, transgenic Drosophila functional assays, in vitro Pbx1 interaction The EMBO journal High 8635464
1998 HOXA5 and HOXB7 are expressed in cerebellar Purkinje cells and synergistically activate the Purkinje cell-specific pcp-2(L7) promoter via TAAT-containing sequence elements (L7ATE), as shown by co-transfection assays. RT-PCR cloning, co-transfection transcriptional activation assays Journal of neurobiology Medium 9740027
1998 Hoxa5 homeotic transformations of the cervicothoracic skeleton are confined to C3–T2, corresponding to the major transcript domain; Cdx/Hoxa4 mutations alter Hoxa5 expression in cis in the cervicothoracic prevertebral column, and compound Hoxa4/Hoxa5 heterozygotes show Hoxa5-like transformations, demonstrating transcriptional interference and regional autoregulation. Genetic epistasis in compound mutant mice, in situ hybridization Developmental dynamics High 9603431
1999 Constitutive expression of HOXA5 in human CD34+ hematopoietic progenitors inhibits erythropoiesis and promotes myelopoiesis, diverting differentiation at a multipotent progenitor stage; erythroid progenitor (BFU-E) frequency was significantly reduced with no change in total CFU numbers. Retroviral transduction of CD34+ and CD34+CD38- cells, immunophenotyping, morphological analysis, clonal analysis Blood High 10397719
2000 HOXA5 transcriptionally activates the p53 promoter; transient transfection of HOXA5 activated the p53 promoter, and HOXA5 expression in wild-type p53 (but not p53-null) breast cancer cells induced apoptosis; coordinate loss of HOXA5 and p53 expression occurs in breast tumors with HOXA5 promoter methylation. Transient transfection reporter assay, promoter analysis, cell death assay, bisulfite methylation analysis Nature High 10879542
2000 HOXA5 transcriptionally activates the progesterone receptor (PR) promoter via a single HOXA5-binding site; HOXA5 binds directly to this site in the PR promoter, and this activity is specific to HOXA5 (not HOXB4, -B5, or -B7); induced HOXA5 expression elevates endogenous PR mRNA in MCF-7 cells. Promoter deletion and mutation analysis, transient transfection assays, gel-shift/DNA binding assays The Journal of biological chemistry High 10875927
2002 Hoxa5 acts in the stomach mesenchyme and controls mesenchymal-epithelial signaling; loss of Hoxa5 function perturbs expression of sonic hedgehog, Indian hedgehog, TGF-β family members, and FGF10, leading to defective gastric epithelial cell specification. Hoxa5-/- mouse analysis, histology, in situ hybridization, molecular marker expression Development High 12163410
2002 Hoxa5 interacts genetically with Pax1 in vertebral patterning and acromion morphogenesis; Hoxa5 ensures Pax1 expression at the correct time/position, and has a distinctive role in specifying perichondrial and chondrogenic cell lineages in a Sox9-dependent manner. Compound mutant mouse analysis, expression studies, genetic epistasis Developmental biology High 11900462
2002 Hoxa5 overexpression in transgenic mice (via Hoxb2 regulatory elements) causes postnatal dwarfism associated with 12-fold increase in liver IGFBP1 mRNA and 50% decrease in IGF1; Hoxa5 directly interacts with Forkhead box transcription factors FKHR and FoxA2/HNF3β (pull-down in vitro and after co-expression), and context-dependently modulates IGFBP1 promoter activity. Transgenic mouse overexpression, pull-down interaction assays, transfection reporter assays Development High 12163409
2003 Loss of Hoxa5 function non-cell-autonomously perturbs thyroid gland development; follicle formation and thyroglobulin processing are abnormal, and expression of Nkx2.1, Pax8, Titf2, thyroglobulin, and thyroperoxidase is affected in Hoxa5-/- thyroid. Hoxa5-/- mouse phenotypic analysis, immunohistochemistry, molecular marker expression Developmental dynamics High 12815622
2004 HOXA5-induced apoptosis in p53-mutant breast cancer cells (Hs578T) is mediated specifically by caspases 2 and 8; caspase 2- and 8-specific inhibitors and siRNAs blocked HOXA5-induced cell death, whereas caspase 1, 3, 6, 9 inhibitors had no effect; HOXA5 sensitizes cells to TNFα-induced apoptosis by at least 100-fold. Inducible HOXA5 expression, caspase inhibitor panel, siRNA knockdown of caspases, western blot Molecular and cellular biology High 14701762
2004 HOXA5 physically interacts with the anti-apoptotic protein Twist; HOXA5 can partially restore Twist-mediated inhibition of p53 target genes, both through transcriptional upregulation of p53 and through direct protein-protein interaction with Twist, thereby modulating p53 homeostasis in breast cancer cells. Co-immunoprecipitation, p53-promoter reporter assay, gamma-irradiation functional assay The Journal of biological chemistry High 15545268
2005 Cdx proteins bind directly to two conserved sites in a 164-bp element within the Hoxa5 mesodermal enhancer (MES) and repress Hoxa5 expression caudally; mutating the Cdx-binding sites causes caudal expansion of the transgene expression domain; Cdx4 is the primary posterior repressor of Hoxa5. In vitro DNA binding assays, transgenic mouse reporter analysis, binding site mutagenesis Molecular and cellular biology High 15684390
2005 Microarray analysis identified 306 genes modulated ≥2-fold by HOXA5 induction; pleiotrophin was confirmed as a direct transcriptional target: HOXA5 binds directly to one site on the pleiotrophin promoter by gel-shift and chromatin immunoprecipitation assays, and activates the promoter in transient transfection assays. Oligonucleotide microarray, promoter cloning, transient transfection, ChIP, gel-shift assay The Journal of biological chemistry High 15757903
2006 HOXA5 transcriptionally activates hMLH1 (MutL homolog 1) in breast cancer cells; HOXA5 binds to the hMLH1 promoter in vivo (ChIP), transactivates the hMLH1 promoter-reporter construct, and HOXA5 expression increases mismatch repair activity in MCF-7 cells. Yeast overexpression screen, promoter-reporter transient transfection, ChIP, in vivo repair assay Neoplasia High 16756717
2006 CALM-AF10 leukemic transformation requires hDOT1L; hDOT1L upregulates Hoxa5 through H3K79 methylation at the Hoxa5 gene, and prevents nuclear export of CALM-AF10; knockdown of Hoxa5 impairs CALM-AF10-mediated transformation, establishing Hoxa5 as a critical downstream effector. Retroviral transformation assay, ChIP for H3K79me, shRNA knockdown, nuclear export assays Nature cell biology High 16921363
2006 Hoxa5 function is restricted to the mammary stroma; loss of Hoxa5 accelerates lobuloalveolar epithelium development; reciprocal mammary gland transplantation established that Hoxa5-/- stroma cannot support normal wild-type epithelial proliferation, demonstrating mesenchymal-epithelial crosstalk. Hoxa5-/- mouse analysis, reciprocal mammary epithelium grafting experiments Developmental dynamics High 16607641
2006 Loss of Hoxa5 function in lung mesenchyme leads to postnatal emphysema-like alveogenesis failure; defective alveolar myofibroblast precursor motility in embryonic lung causes mispositioning and abnormal elastin deposition postnatally; altered goblet cell specification pre-birth leads to goblet cell hyperplasia and mucus hypersecretion. Hoxa5-/- mouse histological, biochemical, and cell biological analysis The American journal of pathology High 17003488
2007 HOXA5 acts downstream of RARβ: a retinoic acid response element (RARE) in the 3' region of HOXA5 binds RARβ directly (ChIP assay); RARβ overexpression enhances RA-mediated HOXA5 induction; RARβ knockdown abolishes RA-induced HOXA5 expression; HOXA5 knockdown partially abrogates retinoid-induced apoptosis. ChIP, RARβ overexpression and siRNA knockdown, reporter assays, apoptosis assays Cancer research High 17804711
2007 HoxA5 stabilizes adherens junctions in hemangioma endothelial cells by increasing Akt1 mRNA and protein expression and down-regulating PTEN; constitutively active Akt1 phenocopies HoxA5-mediated retention of β-catenin in adherens junctions and reduced permeability. HoxA5 stable expression in EOMA cells, in vivo tumor growth, 3D culture, β-catenin localization, Akt activity assays Cell adhesion & migration Medium 19262140
2007 miR-130a directly targets the 3'-UTR of HOXA5 and downregulates its expression and antiangiogenic activity in vascular endothelial cells; a miR-130a binding site in the HOXA5 3'-UTR was identified by genome-wide analysis and confirmed functionally. Luciferase reporter assay with HOXA5 3'-UTR, miR-130a forced expression, angiogenesis assays Blood High 17957028
2012 Loss of Hoxa5 function in lung mesenchyme promotes goblet cell metaplasia via Notch signaling; goblet cells arise from transdifferentiation of Clara cells; Notch1 and HEY2 are upregulated in Hoxa5-/- airways; in vivo γ-secretase inhibitor treatment attenuates goblet cell metaplasia. Hoxa5-/- mouse, naphthalene injury model, Notch pathway analysis, pharmacological inhibition in vivo Biology open High 23213461
2013 RA-induced HOXA5 expression is co-regulated post-transcriptionally: miR-130a (a c-Myc target) represses HOXA5 translation under basal conditions; RA treatment degrades c-Myc (proteasome-dependent), reducing miR-130a and de-repressing HOXA5; HuR binds the 3'-UTR of HOXA5 mRNA and stabilizes it upon RA treatment. RNA-binding protein pulldown, miRNA inhibition/overexpression, mRNA stability assays, western blot Cellular signalling High 23528537
2013 Hoxa5 and Hoxb5 are partially functionally redundant in lung morphogenesis; compound Hoxa5;Hoxb5 four-allele mutants display aggravated lung phenotype with lethality at birth; Hoxa5-exclusive expression in trachea and phrenic motor column underlies Hoxa5-specific trachea and diaphragm phenotypes. Compound Hoxa5;Hoxb5 mutant mice, histology, molecular analysis American journal of physiology. Lung cellular and molecular physiology High 23585229
2015 HOXA5 represses intestinal stem cell fate by inhibiting Wnt signaling; Wnt pathway suppresses HOXA5 to maintain stemness; re-expression of HOXA5 in colon cancer eliminates cancer stem cell phenotype; retinoids induce HOXA5 expression and trigger tumor regression by enforcing differentiation. In vivo mouse intestine Hoxa5 loss- and gain-of-function, Wnt reporter assays, cancer stem cell functional assays, retinoid treatment Cancer cell High 26678341
2015 HOXA5 inhibits lung cancer cell migration, invasion, and filopodia formation in vitro and metastasis in vivo; genome-wide transcriptomics indicated HOXA5 binds promoters of cytoskeleton-related genes and downregulates their mRNA and protein. Ectopic HOXA5 expression, invasion/migration assays, in vivo metastasis model, transcriptomic and pathway analysis, promoter binding analysis PloS one Medium 25875824
2015 JARID1B (H3K4 demethylase) represses HOXA5 in endothelial cells by occupying the HOXA5 promoter and reducing H3K4 methylation; JARID1B knockdown or inhibition induces HOXA5 expression; this suppression of HOXA5 maintains endothelial angiogenic capacity. shRNA knockdown, ChIP (H3K4me at HOXA5 promoter), pharmacological JARID1B inhibition, retinal angiogenesis in endothelial-specific Jarid1b knockout mice Arteriosclerosis, thrombosis, and vascular biology High 26023081
2017 HOXA5 cooperates with STAT3 to transcriptionally activate PD-L1 in melanoma cells; HDAC8 inhibition increases activity of the PD-L1 promoter fragment enriched with HOXA5 and STAT3 binding sites; HOXA5 and STAT3 are physically associated (co-IP) and interdependent for PD-L1 transactivation; HOXA5 or STAT3 knockdown abolishes PD-L1 upregulation by HDAC8 inhibition. Co-immunoprecipitation, promoter-reporter assay, siRNA knockdown, T-cell functional assay The Journal of investigative dermatology High 29174371
2018 HOXA5 promotes adipocyte differentiation partly by inhibiting the PKA/HSL signaling pathway; CEBPβ binds the Hoxa5 promoter and inhibits its methylation; HOXA5 transcriptionally activates Fabp4 (a positive regulator of adipocyte differentiation); these were shown by dual luciferase assay and chromatin binding. Luciferase assay, qPCR, western blot, lipid accumulation assay Cellular physiology and biochemistry Medium 29439250
2019 HOTAIR lncRNA recruits DNMT3b to the HOXA5 promoter, increasing its methylation and silencing HOXA5 expression in AML cells; silencing HOTAIR demethylates the HOXA5 promoter, restores HOXA5 expression, reduces proliferation, and induces apoptosis. ChIP/methylation assays, siRNA knockdown, gene expression analysis, xenograft model Cancer cell international Medium 31168296
2019 CDX2 is a transcription factor that binds the HOXA5 promoter; CAF-derived exosomal miR-181d-5p targets CDX2, which in turn reduces HOXA5 expression, promoting EMT in breast cancer cells; ChIP and dual luciferase reporter assays confirmed CDX2 binding to the HOXA5 promoter. ChIP, dual luciferase reporter assay, exosome co-culture, xenograft model Molecular therapy. Nucleic acids Medium 31955007
2019 Hoxa5 alleviates obesity-induced adipose inflammation by inhibiting the eIF2α/PERK ER stress signaling pathway in adipocytes and by transcriptionally activating PPARγ to promote M2 macrophage polarization. Hoxa5 overexpression in adipocytes, transcriptome sequencing, pathway analysis, macrophage polarization assays Journal of cellular and molecular medicine Medium 31441588
2020 Sp1 transcriptionally activates miR-130b-3p which then directly targets HOXA5 to suppress its expression in hepatocellular carcinoma; ChIP and luciferase assays confirmed Sp1 binding to the miR-130b-3p promoter and miR-130b-3p binding to the HOXA5 3'-UTR; HOXA5 knockdown promotes HCC angiogenesis in vitro and in vivo. Luciferase reporter assay, ChIP, tube formation assay, xenograft Theranostics Medium 32373208
2021 HINT1 suppresses HOXA5 expression by inhibiting PKCβ1 membrane translocation and phosphorylation via direct interaction, thereby attenuating the MEK/ERK/YY1 signaling pathway that drives HOXA5 transcription; HOXA5 mediates cardiac hypertrophy through TGF-β signaling; AAV9-shHoxa5 abolished the cardioprotective effect of HINT1. Co-immunoprecipitation (HINT1-PKCβ1), cellular fractionation, AAV9-mediated cardiac-specific overexpression, shRNA knockdown in vivo, RNA-seq, transverse aortic constriction model Circulation High 34098726
2021 HOXA5 transactivates p53 by directly binding to the ATTA-rich core motif in the p53 promoter (ChIP PCR assay) in hypertrophic scar-derived fibroblasts; HOXA5 overexpression reduces proliferation and collagen synthesis, increases apoptosis, and elevates p21 and Mdm2; p53 silencing partially attenuates HOXA5-mediated effects. Luciferase reporter assay, ChIP PCR, siRNA knockdown, cell proliferation/apoptosis assays Cell death & disease High 33414417
2022 In renal cell carcinoma, HOXA5 suppresses EMT by binding to the SNAI2 (Slug) gene promoter together with DNMT3A, increasing Slug promoter methylation and silencing its expression; this was confirmed by ChIP, immunoblotting, and methylated DNA immunoprecipitation. ChIP, methylated DNA immunoprecipitation, luciferase reporter assay, GSEA, transwell/CCK-8 assays Molecular cancer High 36536414
2024 HOXA5 represses Jag1 transcription by directly binding to the JAG1 gene promoter; loss of HOXA5 (via DNA hypermethylation) derepresses JAG1, activating JAG1-NOTCH signaling and promoting kidney fibrosis; conditional Hoxa5 knockout aggravated fibrosis, conditional knockin alleviated it. ChIP (HOXA5 at JAG1 promoter), conditional KO and KI in kidney proximal tubules, genome-wide methylation analysis, 5-Aza rescue Kidney international High 38521405

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1991 Regionally restricted developmental defects resulting from targeted disruption of the mouse homeobox gene hox-1.5. Nature 755 1673020
1991 Disruption of the Hox-1.6 homeobox gene results in defects in a region corresponding to its rostral domain of expression. Cell 637 1680563
2000 Compromised HOXA5 function can limit p53 expression in human breast tumours. Nature 402 10879542
2007 Regulation of angiogenesis through a microRNA (miR-130a) that down-regulates antiangiogenic homeobox genes GAX and HOXA5. Blood 386 17957028
1990 Variations of cervical vertebrae after expression of a Hox-1.1 transgene in mice. Cell 347 1970515
1992 Identification of a retinoic acid responsive enhancer 3' of the murine homeobox gene Hox-1.6. Mechanisms of development 245 1360810
1989 Craniofacial abnormalities induced by ectopic expression of the homeobox gene Hox-1.1 in transgenic mice. Cell 240 2568891
1990 The segment-specific gene Krox-20 encodes a transcription factor with binding sites in the promoter region of the Hox-1.4 gene. The EMBO journal 190 1969796
1989 Transgenic mice overexpressing the mouse homoeobox-containing gene Hox-1.4 exhibit abnormal gut development. Nature 185 2563568
1989 Mouse homeo-genes within a subfamily, Hox-1.4, -2.6 and -5.1, display similar anteroposterior domains of expression in the embryo, but show stage- and tissue-dependent differences in their regulation. Development (Cambridge, England) 184 2576400
2015 HOXA5 Counteracts Stem Cell Traits by Inhibiting Wnt Signaling in Colorectal Cancer. Cancer cell 180 26678341
2012 MicroRNA-196a promotes non-small cell lung cancer cell proliferation and invasion through targeting HOXA5. BMC cancer 168 22876840
1993 Specification of axial identity in the mouse: role of the Hoxa-5 (Hox1.3) gene. Genes & development 167 7901120
2006 Leukaemic transformation by CALM-AF10 involves upregulation of Hoxa5 by hDOT1L. Nature cell biology 147 16921363
2019 MicroRNA-181d-5p-Containing Exosomes Derived from CAFs Promote EMT by Regulating CDX2/HOXA5 in Breast Cancer. Molecular therapy. Nucleic acids 144 31955007
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