Affinage

HOXA10

Homeobox protein Hox-A10 · UniProt P31260

Length
410 aa
Mass
42.4 kDa
Annotated
2026-04-28
100 papers in source corpus 36 papers cited in narrative 36 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

HOXA10 is a homeodomain transcription factor that orchestrates cell fate decisions in uterine receptivity, hematopoiesis, osteoblastogenesis, and muscle stem cell maintenance by directly binding promoter cis-elements to activate or repress context-specific target genes. In the uterus, HOXA10 is essential for embryo implantation and decidualization, mediating progesterone-induced endometrial differentiation and regulating targets including ITGB3, KLF9, FKBP4, and FoxM1 (PMID:7700356, PMID:10981664, PMID:14648870, PMID:20463357). In hematopoietic cells, HOXA10 expands stem cell repopulating capacity at moderate levels while blocking erythroid/megakaryocyte differentiation at high levels, and represses phagocyte oxidase genes (CYBB, NCF2) in undifferentiated myeloid cells through HDAC recruitment—a repression relieved by cytokine-induced tyrosine phosphorylation of the homeodomain and opposed by SHP2 phosphatase-mediated dephosphorylation (PMID:17234739, PMID:16210632, PMID:17138561). HOXA10 transcriptional activity is further modulated by PCAF-mediated acetylation at K338/K339 that inhibits DNA binding, by calpain-7-dependent proteolytic degradation via a PEST motif, and by Pbx1/HDAC complexes that antagonize HOXA10-driven chromatin hyperacetylation at osteogenic gene promoters (PMID:24037888, PMID:29459744, PMID:20439491).

Mechanistic history

Synthesis pass · year-by-year structured walk · 19 steps
  1. 1995 High

    The foundational question of HOXA10's in vivo requirement was answered: Hoxa10 knockout mice revealed essential, non-redundant roles in axial patterning, male gonadal descent, and female fertility, establishing that HOXA10 functions in reproductive tract morphogenesis and implantation.

    Evidence Targeted gene disruption in mice with histological and embryo transfer analysis

    PMID:7700356

    Open questions at the time
    • Molecular targets of HOXA10 in the uterus were unknown
    • Whether the fertility defect was uterine-autonomous or oviductal was unresolved
    • No downstream transcriptional targets identified
  2. 2000 High

    Gain- and loss-of-function experiments in the uterus demonstrated that maternal HOXA10 expression is both necessary and sufficient for implantation efficiency, resolving the question of whether HOXA10 acts at the implantation step rather than earlier embryonic events.

    Evidence In vivo uterine transfection of antisense or expression constructs in pregnant mice

    PMID:10981664

    Open questions at the time
    • Direct transcriptional targets mediating implantation were not identified
    • Whether HOXA10 acts in epithelium versus stroma was unresolved
  3. 2001 High

    Retroviral overexpression in human CD34+ cells established that HOXA10 profoundly blocks erythroid and B-cell differentiation while enhancing myeloid blast formation, revealing a dose-dependent role in hematopoietic lineage commitment.

    Evidence Retroviral transduction of human cord blood CD34+ cells with in vitro colony assays and NOD/SCID xenograft repopulation

    PMID:11290589

    Open questions at the time
    • Whether HOXA10 expands true HSCs or committed progenitors was unclear
    • Direct transcriptional targets in HSCs were unknown
  4. 2004 Medium

    HOXA10 was shown to mediate progesterone's effects on endometrial differentiation, as its overexpression in ovariectomized mice phenocopied progesterone-induced calcitonin and prolactin expression, positioning HOXA10 as a critical effector of steroid hormone signaling in the uterus.

    Evidence In vivo uterine transfection in ovariectomized, estrogen-primed mice

    PMID:14648870

    Open questions at the time
    • Whether HOXA10 directly activates calcitonin/prolactin promoters was not tested
    • Upstream regulation of HOXA10 by progesterone receptor was not dissected
  5. 2005 High

    The mechanism by which HOXA10 controls myeloid differentiation was elucidated: HOXA10 directly represses phagocyte oxidase genes (CYBB, NCF2) by binding their promoters and recruiting HDACs, with tyrosine phosphorylation of the homeodomain relieving repression during differentiation—establishing a post-translational switch controlling HOXA10 DNA-binding activity.

    Evidence Reporter assays, EMSA, ChIP, homeodomain tyrosine mutagenesis, HDAC activity assays in myeloid cells

    PMID:16210632

    Open questions at the time
    • The kinase responsible for homeodomain tyrosine phosphorylation was not identified
    • Whether tyrosine phosphorylation affects all HOXA10 targets or only phagocyte oxidase genes was unknown
  6. 2006 High

    SHP2 phosphatase was identified as the enzyme maintaining HOXA10 in its dephosphorylated, DNA-binding-competent state in undifferentiated myeloid cells, and constitutively active SHP2 mutations sustained HOXA10-mediated repression throughout differentiation, linking gain-of-function SHP2 to impaired innate immunity.

    Evidence Co-immunoprecipitation, phosphatase assays, constitutively active SHP2 mutant expression in myeloid cells

    PMID:17138561

    Open questions at the time
    • The specific tyrosine residues dephosphorylated by SHP2 on HOXA10 were not mapped biochemically
    • In vivo relevance of the SHP2-HOXA10 axis in human myeloid disorders was not established
  7. 2006 High

    HOXA10 was established as a tumor suppressor in endometrial carcinoma: enforced expression inhibited invasion in vitro and tumor dissemination in vivo by repressing Snail and inducing E-cadherin, while promoter hypermethylation correlated with HOXA10 silencing in advanced tumors.

    Evidence Forced expression in carcinoma lines, nude mouse xenograft, Matrigel invasion, bisulfite sequencing

    PMID:16424022

    Open questions at the time
    • Whether HOXA10 directly binds the Snail promoter was not shown
    • Causal role of methylation in tumor progression was correlative
  8. 2007 High

    HOXA10 was shown to directly activate Runx2 and osteoblastic phenotypic genes by binding promoter Hox elements and promoting chromatin hyperacetylation and H3K4 trimethylation, functioning independently of Runx2 in Runx2-null cells—establishing HOXA10 as an autonomous osteogenic transcription factor.

    Evidence Reporter assays, ChIP, siRNA, Runx2-null cell complementation, chromatin modification analysis

    PMID:17325044

    Open questions at the time
    • Identity of the methyltransferase recruited by HOXA10 was unknown
    • Whether HOXA10 is required for osteoblastogenesis in vivo was not tested
  9. 2007 High

    A controlled transgenic system demonstrated that intermediate HOXA10 levels expand HSC repopulating capacity ~15-fold while high levels block erythroid/megakaryocyte development, and identified Dkk-1 and Gfi-1 as direct transcriptional targets, resolving the dose-dependent nature of HOXA10 in HSC biology.

    Evidence Doxycycline-inducible transgenic mouse, bone marrow transplantation, ChIP, transcriptional activation assays

    PMID:17234739

    Open questions at the time
    • Mechanism of dose-dependent target selectivity was unknown
    • Whether Dkk-1 activation mediates HSC expansion was not tested by epistasis
  10. 2008 Medium

    SHP2 and HOXA10 were shown to cooperate in AML progression: constitutively active SHP2 sustained HOXA10-mediated repression of gp91PHOX/p67PHOX and activation of the anti-apoptotic phosphatase DUSP4/Mkp2 throughout myelopoiesis, providing a mechanistic basis for leukemogenic synergy.

    Evidence Murine bone marrow transplantation with retroviral co-expression of SHP2 and HOXA10

    PMID:19022774

    Open questions at the time
    • Whether DUSP4 is a direct HOXA10 transcriptional target was not confirmed by ChIP
    • Human AML relevance was not validated
  11. 2010 High

    The mechanism by which Pbx1 opposes HOXA10 at osteogenic gene promoters was defined: Pbx1 occupies promoters and recruits HDACs that block HOXA10-induced chromatin hyperacetylation and CBP/p300 recruitment, establishing Pbx1 as a chromatin-level antagonist of HOXA10-driven osteoblast differentiation.

    Evidence ChIP, shRNA knockdown of Pbx1, reporter assays with Pbx-site mutations in mesenchymal cells

    PMID:20439491

    Open questions at the time
    • Whether HOXA10 and Pbx1 physically interact or compete for adjacent sites was not resolved
    • In vivo bone phenotype of Pbx1 loss in osteoblasts was not tested
  12. 2011 High

    Two new direct transcriptional targets of HOXA10 in myeloid cells were identified—ARIH2/Triad1 (an E3 ubiquitin ligase antagonizing myeloproliferation) and CDX4 (forming a positive feedback loop with HOXA10)—revealing how HOXA10 simultaneously restrains proliferation and amplifies its own signaling circuit.

    Evidence ChIP, promoter reporter assays with cis-element mutagenesis, Triad1 and Cdx4 knockdown in myeloid progenitors

    PMID:21454682 PMID:21471217

    Open questions at the time
    • Whether the CDX4-HOXA10 feedback loop operates in vivo in HSCs was not tested
    • Substrates of Triad1 downstream of HOXA10 were not identified
  13. 2012 High

    HOXA10 was found to directly activate FGF2 transcription in myeloid progenitors, establishing an autocrine FGF2→PI3K→β-catenin signaling axis that drives cytokine hypersensitivity, linking HOXA10 transcriptional activity to a specific paracrine/autocrine growth factor pathway.

    Evidence ChIP, reporter assays, Fgf2 neutralization, PI3K inhibition, proliferation assays

    PMID:22493287

    Open questions at the time
    • Whether FGF2 activation contributes to HSC expansion or only to myeloid progenitor proliferation was unknown
    • Role of this axis in AML was not tested
  14. 2013 High

    The post-translational modification landscape of HOXA10 was expanded: PCAF acetyltransferase was shown to acetylate HOXA10 at K338/K339, inhibiting its transcriptional activation of ITGB3 and impairing embryo adhesion, providing a molecular explanation for reduced endometrial receptivity in endometriosis.

    Evidence Co-IP, site-directed mutagenesis of K338/K339, ChIP, luciferase reporter, BeWo spheroid attachment assay

    PMID:24037888

    Open questions at the time
    • Whether PCAF acetylation affects HOXA10 activity at non-ITGB3 targets was not tested
    • Deacetylase responsible for reversing HOXA10 acetylation was not identified
  15. 2015 High

    In vivo rescue experiments in Hoxa10 knockout mice showed that HOXA10 is dispensable for steady-state granulopoiesis but essential for restraining emergency granulopoiesis through Triad1/ARIH2 activation, with re-expression of Triad1 rescuing the lethal phenotype and HoxA9 antagonizing ARIH2 transcription.

    Evidence Hoxa10 knockout mice with emergency granulopoiesis challenge, retroviral Triad1 rescue in bone marrow

    PMID:25895533

    Open questions at the time
    • Mechanism by which emergency signals override HOXA10-Triad1 axis was not defined
    • Whether HoxA9/HoxA10 ratio determines ARIH2 output in human myeloid cells was not confirmed
  16. 2017 High

    HOXA10 was found to regulate trophoblast invasion through a paracrine mechanism: its downregulation in decidual cells after implantation increases LIF/IL-6 secretion, activating STAT3 and MMP expression in trophoblasts, revealing a non-cell-autonomous role for HOXA10 decline in implantation progression.

    Evidence HOXA10 depletion in decidual cells, conditioned medium transfer, STAT3 phosphorylation analysis, STAT3 knockdown rescue

    PMID:28520923

    Open questions at the time
    • Whether HOXA10 directly represses LIF and IL-6 promoters was not shown
    • In vivo validation in implantation models was not performed
  17. 2018 High

    A proteolytic regulation mechanism was identified: calpain-7 directly cleaves HOXA10 through a PEST sequence in a Ca²⁺-dependent manner, reducing HOXA10 protein stability and ITGB3 expression; PEST deletion abolished degradation, establishing a new post-translational control axis for HOXA10 turnover.

    Evidence Co-IP, PEST mutagenesis, calpain inhibitor ALLN rescue, in vivo mouse implantation assay

    PMID:29459744

    Open questions at the time
    • Physiological signals triggering calpain-7-mediated HOXA10 degradation in the uterus were unknown
    • Whether calpain-7 regulates HOXA10 in non-uterine contexts was not tested
  18. 2021 High

    HOXA10 was shown to maintain genomic stability in somite-derived muscle satellite cells; conditional inactivation caused mitotic catastrophe and impaired muscle regeneration specifically in trunk muscles but not cranial-derived muscles, revealing a tissue-of-origin-specific essential function beyond transcriptional regulation of differentiation genes.

    Evidence Satellite cell-specific conditional Hoxa10 knockout mice, FACS, DNA methylation analysis, genomic instability assays, regeneration assays

    PMID:34108202

    Open questions at the time
    • Direct targets mediating genomic stability in satellite cells were not identified
    • Whether HOXA10 acts through chromatin organization or DNA repair pathways to prevent mitotic catastrophe was unknown
  19. 2021 Medium

    In cancer contexts, HOXA10 was linked to epitranscriptomic regulation: it transcriptionally activates ALKBH5 (m6A eraser) in ovarian cancer and TGFB2 in gastric cancer, connecting HOXA10 to m6A-dependent mRNA regulation and TGFβ/Smad-driven EMT pathways.

    Evidence ChIP, MeRIP-seq, RIP, luciferase reporters, in vivo xenograft models

    PMID:33563300 PMID:34496932

    Open questions at the time
    • Whether HOXA10 regulation of m6A machinery is relevant outside cancer contexts is unknown
    • Specificity of HOXA10 for ALKBH5 versus other m6A enzymes was not tested
    • Single-lab findings without independent replication

Open questions

Synthesis pass · forward-looking unresolved questions
  • A unified structural and genome-wide mechanistic model of HOXA10 target selectivity—explaining how post-translational modifications (phosphorylation, acetylation), cofactor interactions (Pbx1, HDACs, CBP/p300), and chromatin context dictate which genes are activated versus repressed in different cell types—remains to be established.
  • No structural model of HOXA10-DNA or HOXA10-cofactor complexes exists
  • Genome-wide binding maps (ChIP-seq) across cell types have not been published
  • How HOXA10 maintains genomic stability in satellite cells at the molecular level is unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 10 GO:0003677 DNA binding 3
Localization
GO:0005634 nucleus 4
Pathway
R-HSA-1266738 Developmental Biology 4 R-HSA-1474165 Reproduction 4 R-HSA-1643685 Disease 4 R-HSA-168256 Immune System 3 R-HSA-4839726 Chromatin organization 2
Partners
CAPN7CDX4HDAC1HOXA9KAT2BPBX1PTPN11

Evidence

Reading pass · 36 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1995 Targeted homozygous mutation of Hoxa10 in mice causes anterior homeotic transformation of lumbar vertebrae, bilateral cryptorchidism with spermatogenesis defects in males, and ~80% sterility in females due to embryo death between days 2.5–3.5 post coitum, coinciding with maternal Hoxa10 expression in distal oviductal and uterine epithelium, establishing a role for Hoxa10 in male and female fertility. Targeted gene disruption (knockout mouse), histology, timed embryo analysis Nature High 7700356
2000 Maternal Hoxa10 expression in the uterus is essential for embryo implantation; antisense oligonucleotide knockdown of Hoxa10 in the uterus significantly reduced implantation sites, while constitutive Hoxa10 overexpression increased litter size. In vivo uterine transfection of DNA/liposome complexes with antisense or expression constructs in day-2 pregnant mice Gene therapy High 10981664
2004 In vivo uterine transfection of Hoxa10 in ovariectomized, estrogen-primed mice phenocopied progesterone treatment, inducing epithelial calcitonin and stromal prolactin expression, demonstrating that Hoxa10 mediates progesterone-induced functional differentiation of endometrial epithelium and stroma. In vivo uterine transfection, immunohistochemistry, gene expression analysis in ovariectomized mice Molecular reproduction and development Medium 14648870
2007 HOXA10 activates the Runx2 P1 promoter via a Hox core motif element in response to BMP2, and directly activates osteoblastic phenotypic genes (alkaline phosphatase, osteocalcin, bone sialoprotein); HOXA10 promotes chromatin hyperacetylation and H3K4 trimethylation at these gene promoters and can induce osteoblast genes even in Runx2-null cells. Reporter assays, ChIP, siRNA knockdown, exogenous expression, Runx2-null cell complementation, chromatin remodeling assays Molecular and cellular biology High 17325044
2007 HOXA10 negatively regulates IGFBP1 mRNA expression in human endometrial stromal cells during decidualization; overexpression of HOXA10 decreased IGFBP1 mRNA while siRNA knockdown increased it even in the presence of decidualizing stimuli. Overexpression and siRNA knockdown in human endometrial stromal cells (HSC), qRT-PCR Molecular human reproduction Medium 17350963
2007 Controlled transgenic expression of HOXA10 in mice expanded hematopoietic stem cell (HSC) repopulating capacity ~15-fold after in vitro culture at intermediate levels, while high HOXA10 levels blocked erythroid and megakaryocyte development; HOXA10 binding sites were found in HLF, Dkk-1, and Gata-1, and HOXA10 transcriptionally activated Dkk-1 and Gfi-1. Doxycycline-inducible transgenic mouse model, bone marrow transplantation/repopulation assays, ChIP, transcriptional activation assays Blood High 17234739
2006 Enforced HOXA10 expression in endometrial carcinoma cells inhibited invasive behavior in vitro and tumor dissemination in nude mice by inducing E-cadherin expression through down-regulation of Snail; HOXA10 promoter methylation correlated with reduced expression and higher tumor grade. Forced expression in carcinoma cell lines, nude mouse xenograft model, invasion assay, bisulfite sequencing Cancer research High 16424022
2005 HoxA10 represses transcription of CYBB (gp91phox) and NCF2 (p67phox) in undifferentiated myeloid cells by binding homologous cis-elements in these promoters; repression requires histone deacetylase recruitment; phosphorylation of two tyrosine residues in the HoxA10 homeodomain by cytokine-activated pathways decreases DNA binding and abrogates repression during myeloid differentiation. Reporter assays, EMSA, ChIP, mutagenesis of homeodomain tyrosine residues, HDAC activity assays Journal of immunology High 16210632
2006 SHP2 protein-tyrosine phosphatase dephosphorylates HoxA10 in undifferentiated myeloid cells, maintaining it in a non-phosphorylated state that sustains repression of CYBB and NCF2 transcription; constitutively active SHP2 mutants dephosphorylate HoxA10 throughout differentiation, causing persistent repression. Co-immunoprecipitation, phosphatase activity assays, reporter assays, expression of constitutively active SHP2 mutants The Journal of biological chemistry High 17138561
2008 Constitutively active SHP2 cooperates with HoxA10 overexpression to accelerate progression to AML in a murine bone marrow model; SHP2-mediated HoxA10 dephosphorylation throughout myelopoiesis sustains repression of gp91PHOX/p67PHOX genes and activation of DUSP4 (encoding anti-apoptotic Mkp2). Murine bone marrow transplantation, retroviral co-expression, gene expression assays, reporter assays The Journal of biological chemistry Medium 19022774
2010 Pbx1 forms a complex at osteoblast-related gene promoters (osteocalcin, bone sialoprotein) that includes histone deacetylases, blocking Hoxa10-mediated chromatin hyperacetylation and CBP/p300 recruitment; knockdown of Pbx1 increases H3K9 acetylation and H4 acetylation at these promoters, enhancing osteogenic gene expression. ChIP, shRNA knockdown, reporter assays with Pbx-site mutations, overexpression in mesenchymal cells Molecular and cellular biology High 20439491
2011 HoxA10 directly activates transcription of ARIH2 (encoding the E3 ubiquitin ligase Triad1) via two cis elements in the ARIH2 promoter in myeloid cells, leading to increased protein ubiquitination in HoxA10-overexpressing cells; Triad1 knockdown further increased cytokine-induced proliferation, identifying ARIH2/Triad1 as a HoxA10 target that antagonizes myeloproliferation. Promoter reporter assays, ChIP, Triad1 knockdown, ubiquitination assays The Journal of biological chemistry High 21454682
2011 HoxA10 activates CDX4 transcription via a HoxA10-binding cis element in the CDX4 promoter; Cdx4 in turn activates the HOXA10 promoter via a Cdx4-binding cis element, establishing a positive feedback loop; Cdx4 knockdown decreased cytokine hypersensitivity of HoxA10-overexpressing myeloid progenitors. Reporter assays, ChIP, CDX4 promoter mutagenesis, Cdx4 shRNA knockdown The Journal of biological chemistry High 21471217
2012 HoxA10 directly activates transcription of FGF2 via two cis elements in the proximal FGF2 promoter in myeloid progenitor cells; HoxA10-overexpressing cells showed increased Fgf2 secretion that drove autocrine PI3K-dependent β-catenin increase and cytokine hypersensitivity. Reporter assays, ChIP, Fgf2 neutralization, PI3K inhibition, proliferation assays The Journal of biological chemistry High 22493287
2013 PCAF acetyltransferase directly interacts with HOXA10 and acetylates it at lysine residues K338 and K339, which inhibits HOXA10-mediated transcription of ITGB3 (β3-integrin) and impairs embryo adhesiveness in Ishikawa endometrial cells; PCAF expression is aberrantly high in endometriosis. Co-immunoprecipitation, Western blotting, confocal immunofluorescence, luciferase reporter, ChIP, BeWo spheroid attachment assay, site-specific mutagenesis The Journal of clinical endocrinology and metabolism High 24037888
2010 HOXA10 directly binds the KLF9 promoter (demonstrated by EMSA) and represses KLF9 transcription specifically in endometrial epithelial cells but not stromal cells; mutation of the HOXA10-binding site abolished both binding and repression in reporter assays. EMSA, luciferase reporter assay with promoter mutation, siRNA/overexpression, qRT-PCR, immunohistochemistry Biology of reproduction High 20463357
2005 HOXA9 and HOXA10 overexpression in human CD34+ cord blood cells activated a common transcriptome signature including Wnt pathway genes (Wnt10B, Frizzled 1, Frizzled 5) and other stem-cell genes (ERG, IRX3, ALDH1); HOXA10 specifically repressed heme biosynthesis and globin genes consistent with suppression of erythroid differentiation. Retroviral transduction of CD34+ cells, cDNA microarray, qRT-PCR validation Stem cells Medium 15849172
2001 Retroviral overexpression of HOXA10 in human CD34+ hematopoietic progenitors profoundly impaired myeloid differentiation, almost completely blocked erythroid differentiation, reduced B-cell development by 70% in NOD/SCID mice, and enhanced myelopoiesis with increased blast colony formation. Retroviral transduction of human cord blood/fetal liver CD34+ cells, in vitro colony assays, NOD/SCID xenograft repopulation Blood High 11290589
2012 HOXA10 overexpression in human endometrial stromal cells (HESCs) increased FKBP4 (FKBP52) mRNA and protein levels, while HOXA10 knockdown decreased FKBP4 expression; FKBP4 siRNA reduced IGFBP1 expression during decidualization, placing HOXA10 upstream of FKBP4 in the decidualization pathway. Overexpression, siRNA knockdown, qRT-PCR, Western blotting in HESCs Reproduction Medium 22279148
2008 HOXA10 transcriptionally regulates Calpain5 in endometrial cells; overexpression of HOXA10 increased Calpain5 expression and siRNA knockdown decreased it, with Calpain5 expression also reduced in endometriosis samples consistent with decreased HOXA10. Transfection of HOXA10 expression construct and siRNA in HESC and epithelial cells, qRT-PCR, immunohistochemistry Molecular human reproduction Medium 18829447
2018 Calpain7 (CAPN7) directly interacts with HOXA10 and degrades it via a PEST sequence in a Ca2+-dependent manner; CAPN7 overexpression reduced HOXA10 protein stability and ITGB3 expression, impairing embryo implantation; calpain inhibitor ALLN reversed CAPN7-induced HOXA10 degradation, and deletion of the PEST motif abolished proteolysis. Co-immunoprecipitation, Western blot, luciferase reporter, in vivo mouse implantation assay, PEST sequence mutagenesis, ALLN inhibitor rescue Cell death & disease High 29459744
2015 FoxM1, a Forkhead box transcription factor, acts downstream of Hoxa10 and cyclin D3 during decidualization; conditional FoxM1 deletion in mice caused regional decidualization defects; Hoxa10 regulated transcriptional activity of FoxM1 while cyclin D3 controlled its nuclear translocation in polyploid decidual cells. Conditional knockout mouse, in vivo and in vitro decidualization assays, cell cycle analysis, nuclear translocation experiments Scientific reports Medium 26350477
2004 HOXA10 overexpression in ER-negative BT20 breast cancer cells increased p53 protein expression and reduced invasiveness through Matrigel; estradiol and tamoxifen increased HOXA10 mRNA expression in ER-positive MCF-7 cells. Stable overexpression, Northern/RT-PCR analysis, Matrigel invasion assay, Western blotting Cancer biology & therapy Medium 15044858
2006 Bisphenol A (BPA) increases HOXA10 expression through two mechanisms: directly via the HOXA10 estrogen response element (ERE) and indirectly via the HOXA10 autoregulatory element (ARE); in utero BPA exposure produces a lasting imprint of HOXA10 expression in adult uterine stroma that becomes uncoupled from estrogen stimulation. Luciferase reporter assays with ERE/ARE constructs, ER antagonist (ICI) blocking, antisense blocking, in vivo mouse gestational exposure model FASEB journal Medium 17093138
2011 miR-135a and miR-135b directly target HOXA10 via its 3' UTR in endometrial stromal cells; transfection with miR-135a/b decreased HOXA10 mRNA and protein, while inhibitors increased it; luciferase assays confirmed direct binding to the HOXA10 3' UTR in a cell-type-specific manner. Transfection with miRNA mimics and inhibitors, luciferase reporter with HOXA10 3' UTR, qPCR, Western blot The Journal of clinical endocrinology and metabolism High 21956427
2015 CTCF functions as a negative regulator of HOXA10 promoter activity in breast cancer cells; CTCF occupies the HOXA10 promoter region and maintains H3K27me3 repressive chromatin marks; a 20 bp CTCF binding motif within the HOXA10 promoter was identified by in silico analysis and mutation assay. CTCF overexpression and knockdown, luciferase reporter with promoter mutations, ChIP for H3K27me3 Biochemical and biophysical research communications Medium 26478432
2017 In human and baboon decidua, HOXA10 expression decreases after implantation; HOXA10-depleted decidual cells secrete elevated LIF and IL-6, which activate STAT3 (Tyr705) in trophoblast cells to increase MMP expression and TIMP reduction, thereby promoting trophoblast invasion. HOXA10 depletion in decidual cells, conditioned medium transfer to trophoblast lines, MMP activity assays, STAT3 phosphorylation analysis, STAT3 knockdown rescue Endocrinology High 28520923
2010 HOXA9 and HOXA10 directly activate ID2 promoter transcription in NK/T-cell lines as shown by ChIP and overexpression experiments; EZH2/PRC2 represses HOXA10 expression in T-cell lines (siRNA knockdown of EZH2 enhanced HOXA10 expression); HOXA10 and ID2 overexpression repressed BIM apoptosis factor expression. ChIP, promoter reporter assays, siRNA knockdown of EZH2, EZH2 inhibitor (DZNep), overexpression assays Molecular cancer Medium 20565746
2015 HoxA10 disruption in mice does not significantly alter steady-state granulopoiesis but leads to an overwhelming, fatal emergency granulopoiesis response; re-expression of Triad1 in bone marrow reversed this phenotype, and HoxA9 antagonized ARIH2 transcription opposing HoxA10; differentiation-stage-specific ARIH2 transcription is regulated by tyrosine phosphorylation states of HoxA9 and HoxA10. HOXA10 knockout mice, emergency granulopoiesis induction, bone marrow retroviral Triad1 rescue, ARIH2 reporter assays, phosphorylation analysis Journal of immunology High 25895533
2021 Hoxa10 expression is maintained by DNA hypermethylation of the Hox-A locus in somite-derived satellite cells (muscle stem cells) in adult mice; Hoxa10 inactivation led to genomic instability and mitotic catastrophe specifically in somite-derived satellite cells but not cranial mesoderm-derived satellite cells, impairing regenerative ability of somite-derived muscles. Satellite cell-specific conditional Hoxa10 knockout mice, FACS isolation of satellite cells, DNA methylation analysis, genomic instability assays, muscle regeneration assays Science advances High 34108202
2021 HOXA10 acts as the upstream transcription factor for ALKBH5, forming a regulatory loop; together HOXA10 and ALKBH5 promote m6A demethylation of JAK2 mRNA to activate JAK2/STAT3 signaling and cisplatin resistance in epithelial ovarian cancer cells. MeRIP-seq, RNA-seq, ChIP, RIP, luciferase reporter, in vivo xenograft, siRNA knockdown Journal of experimental & clinical cancer research Medium 34496932
2021 HOXA10 enriches at the TGFB2 promoter to promote its transcription, triggering TGFβ/Smad2/3 signaling; Smad proteins in turn upregulate METTL3 expression; METTL3 mediates HOXA10-driven EMT and lung metastasis in gastric cancer cells. ChIP-qPCR, dual-luciferase reporter, Co-IP, colorimetric m6A assay, in vivo lung metastasis rescue models, Western blot Journal of experimental & clinical cancer research Medium 33563300
2019 HOXA10 knockdown in HCC cells suppresses HDAC1 transcription (via ChIP-confirmed HOXA10 binding at the HDAC1 promoter), increasing p53 acetylation at Lys382, leading to G0/G1 arrest and apoptosis; HDAC1 overexpression rescued the effects of HOXA10 knockdown on proliferation and p53 acetylation. ChIP, luciferase reporter, flow cytometry, siRNA/shRNA knockdown, HDAC1 rescue overexpression, in vivo xenograft Cancer management and research Medium 31440094
2009 HOXA10 expression in OSE (ovarian surface epithelial) cells promotes homophilic cell adhesion, prevents anoikis, stimulates interactions with extracellular matrix proteins vitronectin and fibronectin, and enhances interaction with omental mesothelial cells and fibroblasts that promotes OSE cell growth. Stable HOXA10 induction in OSE cells, adhesion assays, anoikis assays, co-culture with omental cells, growth assays Molecular and cellular endocrinology Medium 20036708
2014 HOXA10 overexpression in endometrial cancer cells increases p21 expression, causing G1 phase cell cycle arrest and decreased proliferation; conversely, HOXA10 knockdown decreases p21, with no effect on p16, p27, Myc, cyclins D1/E, CDK2/4/6. HOXA10 vector transfection and siRNA knockdown, flow cytometry cell cycle analysis, EdU proliferation assay, qRT-PCR and Western blot Medical oncology Medium 24943991
2020 HOXA10 inhibits osteogenic differentiation of periodontal ligament stem cells (hPDLSCs) by promoting DKK1 expression and reducing nuclear β-catenin, antagonizing Wnt/β-catenin signaling; the Wnt activator LiCl reversed HOXA10 overexpression effects and the Wnt inhibitor ICG-001 reversed HOXA10 knockdown effects. Overexpression and knockdown of HOXA10 in hPDLSCs, ALP and alizarin red staining, Western blot for β-catenin/DKK1, LiCl and ICG-001 pharmacological rescue Connective tissue research Medium 32299243

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1995 Sexually dimorphic sterility phenotypes in Hoxa10-deficient mice. Nature 436 7700356
2007 Altered expression of HOXA10 in endometriosis: potential role in decidualization. Molecular human reproduction 181 17350963
2000 Alteration of maternal Hoxa10 expression by in vivo gene transfection affects implantation. Gene therapy 172 10981664
1993 Specification of axial identity in the mouse: role of the Hoxa-5 (Hox1.3) gene. Genes & development 167 7901120
2010 The role of the Hoxa10/HOXA10 gene in the etiology of endometriosis and its related infertility: a review. Journal of assisted reproduction and genetics 151 20821045
2007 HOXA10 controls osteoblastogenesis by directly activating bone regulatory and phenotypic genes. Molecular and cellular biology 141 17325044
1988 Mouse homeobox gene transcripts occupy different but overlapping domains in embryonic germ layers and organs: a comparison of Hox-3.1 and Hox-1.5. Development (Cambridge, England) 134 2904354
2021 ALKBH5-HOXA10 loop-mediated JAK2 m6A demethylation and cisplatin resistance in epithelial ovarian cancer. Journal of experimental & clinical cancer research : CR 122 34496932
1999 Regulation of HOXA-10 and its expression in normal and abnormal endometrium. Molecular human reproduction 112 10460226
2011 MicroRNA 135 regulates HOXA10 expression in endometriosis. The Journal of clinical endocrinology and metabolism 110 21956427
2021 HOXA10 mediates epithelial-mesenchymal transition to promote gastric cancer metastasis partly via modulation of TGFB2/Smad/METTL3 signaling axis. Journal of experimental & clinical cancer research : CR 108 33563300
2006 Deregulation of the HOXA10 homeobox gene in endometrial carcinoma: role in epithelial-mesenchymal transition. Cancer research 108 16424022
1991 Separate elements cause lineage restriction and specify boundaries of Hox-1.1 expression. Development (Cambridge, England) 101 1685116
2004 HOXA10 regulates p53 expression and matrigel invasion in human breast cancer cells. Cancer biology & therapy 100 15044858
2012 miRNA-135a promotes breast cancer cell migration and invasion by targeting HOXA10. BMC cancer 98 22439757
2007 HOXA10 is a critical regulator for hematopoietic stem cells and erythroid/megakaryocyte development. Blood 91 17234739
2005 A new recurrent inversion, inv(7)(p15q34), leads to transcriptional activation of HOXA10 and HOXA11 in a subset of T-cell acute lymphoblastic leukemias. Leukemia 90 15674412
2001 Overexpression of HOXA10 perturbs human lymphomyelopoiesis in vitro and in vivo. Blood 89 11290589
2004 Retinoic acid signaling acts via Hox1 to establish the posterior limit of the pharynx in the chordate amphioxus. Development (Cambridge, England) 88 15576409
2019 Quercetin inhibits cell viability, migration and invasion by regulating miR-16/HOXA10 axis in oral cancer. European journal of pharmacology 82 30639311
2010 Regional development of uterine decidualization: molecular signaling by Hoxa-10. Molecular reproduction and development 76 19921737
1990 Position-specific activity of the Hox1.1 promoter in transgenic mice. Development (Cambridge, England) 75 1971214
2006 Reversal of Hox1 gene subfunctionalization in the mouse. Developmental cell 74 16890163
1987 Murine Hox-1.7 homeo-box gene: cloning, chromosomal location, and expression. Molecular and cellular biology 74 2891029
2006 Salpingectomy increases peri-implantation endometrial HOXA10 expression in women with hydrosalpinx. Fertility and sterility 70 17173899
2014 MiR-135a functions as a tumor suppressor in epithelial ovarian cancer and regulates HOXA10 expression. Cellular signalling 67 24607788
2016 HOXA-10 and E-cadherin expression in the endometrium of women with recurrent implantation failure and recurrent miscarriage. Fertility and sterility 66 27793380
2005 Activation of stem-cell specific genes by HOXA9 and HOXA10 homeodomain proteins in CD34+ human cord blood cells. Stem cells (Dayton, Ohio) 65 15849172
2006 Xenoestrogen exposure imprints expression of genes (Hoxa10) required for normal uterine development. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 64 17093138
2010 Pbx1 represses osteoblastogenesis by blocking Hoxa10-mediated recruitment of chromatin remodeling factors. Molecular and cellular biology 60 20439491
2002 Hydrosalpinx fluid diminishes endometrial cell HOXA10 expression. Fertility and sterility 57 12215336
2003 Expression of Raldh2, Cyp26 and Hox-1 in normal and retinoic acid-treated Ciona intestinalis embryos. Gene expression patterns : GEP 56 12799071
2013 PCAF impairs endometrial receptivity and embryo implantation by down-regulating β3-integrin expression via HOXA10 acetylation. The Journal of clinical endocrinology and metabolism 54 24037888
2002 Conserved regulation of the Caenorhabditis elegans labial/Hox1 gene ceh-13. Developmental biology 53 11820809
1999 Analysis of homeobox gene HOXA10 mutations in cryptorchidism. The Journal of urology 53 10037424
2018 Methylation of the HOXA10 Promoter Directs miR-196b-5p-Dependent Cell Proliferation and Invasion of Gastric Cancer Cells. Molecular cancer research : MCR 48 29453320
2012 FKBP4 is regulated by HOXA10 during decidualization and in endometriosis. Reproduction (Cambridge, England) 48 22279148
2013 HOXA10 and HOXA13 sequence variations in human female genital malformations including congenital absence of the uterus and vagina. Gene 47 23376215
2018 LncRNA H19 regulates the expression of its target gene HOXA10 in endometrial carcinoma through competing with miR-612. European review for medical and pharmacological sciences 46 30070313
2008 Constitutively active SHP2 cooperates with HoxA10 overexpression to induce acute myeloid leukemia. The Journal of biological chemistry 45 19022774
2018 MiR-135a-5p represses proliferation of HNSCC by targeting HOXA10. Cancer biology & therapy 44 29580143
2018 LncHOXA10 drives liver TICs self-renewal and tumorigenesis via HOXA10 transcription activation. Molecular cancer 42 30545354
2012 Retinoic acid-driven Hox1 is required in the epidermis for forming the otic/atrial placodes during ascidian metamorphosis. Development (Cambridge, England) 42 22573621
2010 Reduced expression of HOXA10 in the midluteal endometrium from infertile women with minimal endometriosis. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 42 20971605
2004 Pleiotropic effects of Hoxa10 on the functional development of peri-implantation endometrium. Molecular reproduction and development 41 14648870
2021 Obesity regulates miR-467/HoxA10 axis on osteogenic differentiation and fracture healing by BMSC-derived exosome LncRNA H19. Journal of cellular and molecular medicine 39 33471953
2019 Long noncoding RNA LINC00483/microRNA-144 regulates radiosensitivity and epithelial-mesenchymal transition in lung adenocarcinoma by interacting with HOXA10. Journal of cellular physiology 39 30714135
2021 Hoxa10 mediates positional memory to govern stem cell function in adult skeletal muscle. Science advances 37 34108202
2015 HOXA10 controls proliferation, migration and invasion in oral squamous cell carcinoma. International journal of clinical and experimental pathology 37 26097543
2009 Modulation of HOXA10 and other markers of endometrial receptivity by age and human chorionic gonadotropin in an endometrial explant model. Fertility and sterility 37 19131054
2015 Control of regional decidualization in implantation: Role of FoxM1 downstream of Hoxa10 and cyclin D3. Scientific reports 36 26350477
2006 Activation of SHP2 protein-tyrosine phosphatase increases HoxA10-induced repression of the genes encoding gp91(PHOX) and p67(PHOX). The Journal of biological chemistry 36 17138561
2014 DNA methylation of HOXA10 in eutopic and ectopic endometrium. Human reproduction (Oxford, England) 35 24963168
2010 Polycomb repressor complex 2 regulates HOXA9 and HOXA10, activating ID2 in NK/T-cell lines. Molecular cancer 35 20565746
2018 MicroRNA‑665 suppresses the growth and migration of ovarian cancer cells by targeting HOXA10. Molecular medicine reports 34 30015865
2017 Decrease in Expression of HOXA10 in the Decidua After Embryo Implantation Promotes Trophoblast Invasion. Endocrinology 34 28520923
2012 HoxA10 protein regulates transcription of gene encoding fibroblast growth factor 2 (FGF2) in myeloid cells. The Journal of biological chemistry 34 22493287
2019 The stem cell-specific long noncoding RNA HOXA10-AS in the pathogenesis of KMT2A-rearranged leukemia. Blood advances 33 31867596
2019 MiR-27b-3p promotes migration and invasion in colorectal cancer cells by targeting HOXA10. Bioscience reports 32 31763673
2014 GnRH analogues may increase endometrial Hoxa10 promoter methylation and affect endometrial receptivity. Molecular medicine reports 32 25323439
2010 Identification of aberrant promoter hypomethylation of HOXA10 in ovarian cancer. Journal of cancer research and clinical oncology 32 20151152
2005 Identification and linkage mapping of the genes for the putative homeodomain protein (hox1) and the putative pheromone receptor protein homologue (rcb1) in a bipolar basidiomycete, Pholiota nameko. Current genetics 32 16096791
2018 HOXA10‑AS: A novel oncogenic long non‑coding RNA in glioma. Oncology reports 31 30132568
2022 The roles and expression of HOXA/Hoxa10 gene: A prospective marker of mammalian female fertility? Reproductive biology 30 35550944
2020 CircCTDP1 promotes nasopharyngeal carcinoma progression via a microRNA‑320b/HOXA10/TGFβ2 pathway. International journal of molecular medicine 30 31985027
2019 HOXA10 knockdown inhibits proliferation, induces cell cycle arrest and apoptosis in hepatocellular carcinoma cells through HDAC1. Cancer management and research 29 31440094
2018 Epigenetic Dynamics of HOXA10 Gene in Infertile Women With Endometriosis. Reproductive sciences (Thousand Oaks, Calif.) 29 29592776
2005 HoxA10 represses transcription of the gene encoding p67phox in phagocytic cells. Journal of immunology (Baltimore, Md. : 1950) 29 16210632
2020 Bone-targeted lncRNA OGRU alleviates unloading-induced bone loss via miR-320-3p/Hoxa10 axis. Cell death & disease 28 32427900
2008 Calpain5 expression is decreased in endometriosis and regulated by HOXA10 in human endometrial cells. Molecular human reproduction 28 18829447
2024 m6A/HOXA10-AS/ITGA6 axis aggravates oxidative resistance and malignant progression of laryngeal squamous cell carcinoma through regulating Notch and Keap1/Nrf2 pathways. Cancer letters 27 38369001
2022 LncRNA NEAT1 affects endometrial receptivity by regulating HOXA10 promoter activity. Cell cycle (Georgetown, Tex.) 27 35574918
2017 A long-range interactive DNA methylation marker panel for the promoters of HOXA9 and HOXA10 predicts survival in breast cancer patients. Clinical epigenetics 27 28748001
2015 CTCF negatively regulates HOXA10 expression in breast cancer cells. Biochemical and biophysical research communications 27 26478432
2011 HoxA10 influences protein ubiquitination by activating transcription of ARIH2, the gene encoding Triad1. The Journal of biological chemistry 27 21454682
2007 HOXA10 mutations in congenital absence of uterus and vagina. Fertility and sterility 27 17482600
2020 Silencing of LINC00461 enhances radiosensitivity of lung adenocarcinoma cells by down-regulating HOXA10 via microRNA-195. Journal of cellular and molecular medicine 26 31967713
2019 HOXA10 deteriorates gastric cancer through activating JAK1/STAT3 signaling pathway. Cancer management and research 26 31406476
2017 HOXA7, HOXA9, and HOXA10 are differentially expressed in clival and sacral chordomas. Scientific reports 25 28515451
2008 Evolution of the thyroid: anterior-posterior regionalization of the Oikopleura endostyle revealed by Otx, Pax2/5/8, and Hox1 expression. Developmental dynamics : an official publication of the American Association of Anatomists 25 18386819
2009 Epidermal expression of Hox1 is directly activated by retinoic acid in the Ciona intestinalis embryo. Developmental biology 24 19782671
2004 Homeobox HOXA10 gene analysis in cryptorchidism. Journal of pediatric endocrinology & metabolism : JPEM 24 14960020
2014 Upregulation HOXA10 homeobox gene in endometrial cancer: role in cell cycle regulation. Medical oncology (Northwood, London, England) 23 24943991
2011 HoxA10 activates CDX4 transcription and Cdx4 activates HOXA10 transcription in myeloid cells. The Journal of biological chemistry 23 21471217
2018 Calpain7 impairs embryo implantation by downregulating β3-integrin expression via degradation of HOXA10. Cell death & disease 22 29459744
2008 Molecular switches involving homeodomain proteins, HOXA10 and RUNX2 regulate osteoblastogenesis. Cells, tissues, organs 22 18701816
2006 Over expression of insulin-like 3 does not prevent cryptorchidism in GNRHR or HOXA10 deficient mice. The Journal of urology 22 16753450
2003 Endometrial HOXA10 expression after controlled ovarian hyperstimulation with recombinant follicle-stimulating hormone. Fertility and sterility 22 14505762
2010 HOXA10 inhibits Kruppel-like factor 9 expression in the human endometrial epithelium. Biology of reproduction 21 20463357
2023 Expression of HOXA10 Gene in Women with Endometriosis: A Systematic Review. International journal of molecular sciences 20 37629050
2020 HOXA10 inhibit the osteogenic differentiation of periodontal ligament stem cells by regulating β-catenin localization and DKK1 expression. Connective tissue research 20 32299243
2019 Tumor-Promoting Activity of Long Noncoding RNA LINC00466 in Lung Adenocarcinoma via miR-144-Regulated HOXA10 Axis. The American journal of pathology 20 31381886
2015 HoxA10 Terminates Emergency Granulopoiesis by Increasing Expression of Triad1. Journal of immunology (Baltimore, Md. : 1950) 20 25895533
2006 Thrombin and interleukin-1beta regulate HOXA10 expression in human term decidual cells: implications for preterm labor. The Journal of clinical endocrinology and metabolism 20 16551735
2018 Decreased Expression of HOXA10 May Activate the Autophagic Process in Ovarian Endometriosis. Reproductive sciences (Thousand Oaks, Calif.) 19 29658437
2009 The Müllerian HOXA10 gene promotes growth of ovarian surface epithelial cells by stimulating epithelial-stromal interactions. Molecular and cellular endocrinology 19 20036708
1992 Hox-1.11 and Hox-4.9 homeobox genes. Proceedings of the National Academy of Sciences of the United States of America 19 1348361
2021 hsa_circ_001946 elevates HOXA10 expression and promotes the development of endometrial receptivity via sponging miR-135b. Diagnostic pathology 18 33993878
2021 Long non-coding RNA PSMA3-AS1 promotes glioma progression through modulating the miR-411-3p/HOXA10 pathway. BMC cancer 18 34294084
2024 Role of HOXA10 in pathologies of the endometrium. Reviews in endocrine & metabolic disorders 17 39499452