Affinage

HOXD10

Homeobox protein Hox-D10 · UniProt P28358

Length
340 aa
Mass
38.4 kDa
Annotated
2026-04-28
92 papers in source corpus 30 papers cited in narrative 30 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

HOXD10 is a homeodomain transcription factor that patterns posterior body structures during development and acts as a transcriptional repressor of pro-invasive and proliferative signaling in multiple adult tissue contexts. It binds TAAT-containing DNA motifs through its homeodomain, uses a proline-rich N-terminal activation domain, and forms cooperative complexes with PBX1b/PREP1 to regulate targets including the renin promoter, NOX4, AMOT-p80, and IFIT family genes (PMID:1756725, PMID:7907418, PMID:15792957, PMID:38844470, PMID:25010866). Targeted disruption in mice establishes HOXD10 as essential for hindlimb skeletal identity, lumbosacral motoneuron specification, and mammary gland secretory activation via prolactin receptor–STAT5 signaling, with functional cooperativity among paralogous Hox genes (PMID:9409668, PMID:15305286, PMID:32705545, PMID:11180954). HOXD10 expression is frequently silenced by promoter DNA methylation (mediated by DNMT1/DNMT3B/MeCP2) and by multiple microRNAs (miR-10b, miR-23a), and its loss derepresses RHOC and the AKT/MAPK signaling axis to promote cell invasion and proliferation in diverse cancer types (PMID:34790580, PMID:22293682, PMID:30603114).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1991 High

    Establishing that HOXD10 is a sequence-specific transcription factor that binds TAAT motifs and can transactivate endogenous HOX cluster regulatory elements answered whether HOX4 cluster proteins have autonomous DNA-binding and transcriptional activity.

    Evidence Gel retardation assays and cotransfection reporter assays in cell lines

    PMID:1756725

    Open questions at the time
    • Endogenous genomic targets beyond the HOX cluster were not identified
    • Cooperating cofactors were unknown
  2. 1992 High

    Demonstration that HOXD4 autoregulates its own promoter via two TAAT motifs established a positive-feedback regulatory mechanism within the HOX cluster, addressing how Hox gene expression is maintained after initial activation.

    Evidence Mutagenesis of TAAT motifs, gel-shift assays, and luciferase reporter assays in P19 cells

    PMID:1356763

    Open questions at the time
    • Whether autoregulation occurs in vivo was not confirmed
    • The role of cofactors in autoregulation was not addressed
  3. 1993 High

    Identification of a retinoic acid response element upstream of Hoxd4 and its requirement for RA-induced transcription established how retinoid signaling initiates HOXD gene expression during development.

    Evidence Reporter assays, EMSA for RAR binding, and dominant-negative RAR-alpha in P19 cells

    PMID:8093325

    Open questions at the time
    • Whether this RARE is required in vivo for normal Hoxd4 expression boundaries was not tested
  4. 1994 High

    Mapping a proline-rich N-terminal transcriptional activation domain answered how HOXD10 protein structure separates DNA recognition from transcriptional output.

    Evidence GAL4 fusion assays, deletion/point mutagenesis, and squelching with AP2 in P19 cells

    PMID:7907418

    Open questions at the time
    • No coactivator/corepressor partners of the activation domain were identified
    • Domain function was not validated in vivo
  5. 1997 High

    Knockout of Hoxd10 in mice revealed its essential requirement for hindlimb skeletal identity, sacral vertebral patterning, and lumbosacral motor neuron organization, answering what developmental processes depend on this gene.

    Evidence Gene targeting in mice with skeletal, neural, and behavioral phenotyping

    PMID:9409668

    Open questions at the time
    • Direct transcriptional targets mediating the skeletal and neural phenotypes were not identified
    • Whether Hoxd10 acts cell-autonomously in motoneurons was not resolved
  6. 1999 High

    Double knockouts of Hoxd9/Hoxd10 and Hoxa10/Hoxd10 revealed synergistic phenotypes more severe than single mutants, establishing functional cooperativity among adjacent and paralogous Hox genes in posterior patterning.

    Evidence Double-mutant mice with skeletal, neural, and locomotor analysis

    PMID:10642795 PMID:11180954

    Open questions at the time
    • Whether cooperativity reflects shared targets, cross-regulation, or both was not distinguished
    • Molecular basis of dosage-dependent interaction was unclear
  7. 2004 High

    Ectopic Hoxd10 expression in thoracic chick spinal cord induced lumbosacral motoneuron identity (Lim1, RALDH2), demonstrating sufficiency for motoneuron specification and answering whether Hoxd10 instructs rather than merely permits lumbar identity.

    Evidence In ovo electroporation with immunohistochemistry for regional motoneuron markers and axon tracing

    PMID:15305286

    Open questions at the time
    • Direct Hoxd10 binding to Lim1 or RALDH2 regulatory regions was not shown
    • Whether this sufficiency requires endogenous cofactors was not resolved
  8. 2005 High

    Identification of the HOXD10·PBX1b·PREP1 complex as an activator of the renin promoter (cooperating with Ets-1 and Notch1-ICD) established the first defined cofactor complex and non-Hox target gene for HOXD10.

    Evidence EMSA, reporter assays, and cotransfection in COS-7/As4.1 cells with promoter mutations

    PMID:15792957

    Open questions at the time
    • In vivo relevance for renin expression in juxtaglomerular cells was not demonstrated
    • Whether the PBX1b/PREP1 complex is required for all HOXD10 targets was unknown
  9. 2011 High

    Demonstration that miR-10b directly targets HOXD10 to derepress RhoC and the AKT signaling axis, promoting cancer cell invasion, established the mechanistic link between HOXD10 loss and pro-metastatic signaling — answering how HOXD10 functions as a tumor suppressor.

    Evidence miR-10b overexpression/inhibition, HOXD10 rescue, RhoC knockdown, AKT inhibition, and invasion assays in glioma and gastric cancer cell lines

    PMID:21419107 PMID:22293682

    Open questions at the time
    • Whether HOXD10 directly binds the RHOC promoter to repress transcription was not confirmed
    • In vivo tumor models were not used in the initial studies
  10. 2014 High

    Identification of AMOT-p80 and miR-146a as direct transcriptional targets of HOXD10, and POU2F1 as an upstream transcriptional activator, built out the regulatory circuit of HOXD10 in HNSCC, answering both what HOXD10 regulates and what regulates HOXD10.

    Evidence Luciferase reporter assays for AMOT-p80 and miR-146a promoters; POU2F1 promoter mutagenesis and siRNA in HNSCC cells

    PMID:25010866 PMID:25301728

    Open questions at the time
    • ChIP confirmation of HOXD10 occupancy at AMOT-p80 and miR-146a promoters was not shown
    • Whether POU2F1 regulation is tissue-specific was not addressed
  11. 2020 High

    Hoxd10 knockout mice showed defective mammary gland secretory activation with reduced prolactin receptor expression and STAT5 phosphorylation, revealing a previously unknown systemic role for HOXD10 in lactation that extends beyond its known developmental patterning functions.

    Evidence Hoxd10 KO and Hoxd9/d10 double-KO mice; mammary transplantation; Western blot for STAT5/STAT3 signaling, prolactin receptor, and milk proteins

    PMID:32705545

    Open questions at the time
    • The systemic factor mediating attenuated STAT5 signaling was not identified
    • Direct transcriptional targets of HOXD10 in mammary epithelium were not defined
  12. 2021 Medium

    ChIP-based demonstration that DNMT1, DNMT3B, and MeCP2 are recruited to the HOXD10 promoter to silence it, and that HOXD10 restoration enhances 5-FU chemosensitivity, answered how HOXD10 is epigenetically silenced in cancer and connected this silencing to drug resistance.

    Evidence ChIP for DNMT1/DNMT3B/MeCP2 at HOXD10 promoter; pyrosequencing; demethylation rescue; drug sensitivity assays in CRC cells

    PMID:34790580

    Open questions at the time
    • Whether methylation-mediated silencing is an early or late event in tumorigenesis was not established
    • Single-lab finding without independent replication
  13. 2024 High

    Direct ChIP and reporter assay evidence that HOXD10 binds the NOX4 promoter to repress its transcription, thereby inhibiting ferroptosis and oxidative stress, revealed a new mechanistic axis for HOXD10 in renal fibrosis independent of its known RHOC-related functions.

    Evidence ChIP and dual-luciferase assay for HOXD10-NOX4 binding; AAV-HOXD10 in UUO mouse model; ferroptosis markers in HK-2 cells

    PMID:38844470

    Open questions at the time
    • Whether HOXD10 regulation of NOX4 occurs in developmental or other disease contexts was not tested
    • Genome-wide binding profile for HOXD10 is still lacking

Open questions

Synthesis pass · forward-looking unresolved questions
  • A genome-wide binding map (ChIP-seq) for HOXD10, the structural basis for target gene selectivity among paralogous HOX proteins, and the identity of the systemic factor mediating HOXD10's role in mammary secretory activation remain unresolved.
  • No genome-wide ChIP-seq or CUT&RUN data for HOXD10 are available
  • Structural basis for HOXD10 target selectivity versus other posterior HOX proteins is unknown
  • The systemic mediator of HOXD10 action in lactation is unidentified

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 7 GO:0003677 DNA binding 5
Localization
GO:0005634 nucleus 5
Pathway
R-HSA-74160 Gene expression (Transcription) 6 R-HSA-1266738 Developmental Biology 5 R-HSA-162582 Signal Transduction 4
Partners
GABPAPBX1BPOU2F1PREP1RHOCTBX1
Complex memberships
HOXD10·PBX1b·PREP1

Evidence

Reading pass · 30 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1991 HOX4D (HOXD10) and HOX4C homeoproteins bind to a phylogenetically conserved DNA fragment in the HOX4C/HOX4D intergenic region containing multiple TAAT-related binding sites, and HOX4D and HOX4C transactivate this endogenous sequence in cotransfection experiments, establishing them as sequence-specific transcription factors capable of cross-regulatory interactions within the HOX4 complex. Gel retardation assays (EMSA) and cotransfection transactivation assays in cell lines The EMBO journal High 1756725
1992 HOXD-4 (HOX-4.2/Hoxd-4) protein autoregulates its own promoter by binding specifically to two TAAT/ATTA motifs within a 217 bp conserved element upstream of Hox-4.2; cotransfection of Hox-4.2 expression vector with a reporter driven by this element produced a ~20-fold increase in luciferase activity, an effect specific to Hox-4.2 and not Hox-1.6. Transient cotransfection luciferase reporter assays and gel-shift DNA binding assays in P19 EC cells; mutational analysis of TAAT motifs The EMBO journal High 1356763
1993 A retinoic acid response element (RARE) with sequence 5'-AGGTGA(N)5AGGTCA-3' was identified upstream of murine Hox-4.2 (HOXD4); this element specifically binds retinoic acid receptors (RARs) and is required for RA-induced transcriptional activation of Hox-4.2, as demonstrated by dominant-negative RAR-alpha suppression of RA induction. Transient expression luciferase reporter assays in P19 EC cells; gel-shift assays for RAR binding; dominant-negative RAR-alpha transfection Molecular and cellular biology High 8093325
1994 The HOXD-4 (HOX-4.2) protein contains a proline-rich N-terminal transcriptional activation domain; GAL4 fusion assays mapped activation to this domain, and squelching by the proline-rich transcription factor AP2 confirmed the proline-rich nature of the activation domain. A single homeodomain point mutation abolished transcriptional activity. Transient transfection with GAL4 DNA-binding domain fusions; deletion and point mutational analysis; squelching assays with AP2 in P19 EC cells Nucleic acids research High 7907418
1997 Targeted disruption of Hoxd-10 in mice causes hindlimb-specific locomotor defects including altered gait and adduction, homeotic transformations of sacral vertebrae (S2 onward adopting more anterior morphology), anterior shift of the patella, outward rotation of the lower leg, decreased spinal segments projecting through the sacral plexus, deletion of hindlimb nerves, and a shift in the position of the lumbar lateral motor column — establishing Hoxd-10 as required for regional identity in hindlimb skeletal, muscular, and neural patterning. Gene targeting/knockout in mice; skeletal, muscular, and neural histological analysis; locomotor behavioral assays Development (Cambridge, England) High 9409668
1996 A cis-acting element (region IX) upstream of Hoxd-11 also controls the anterior expression boundary of Hoxd-10; in vivo targeted mutation abolishing nuclear receptor (RAR and COUP-TF) binding to region IX leads to anteriorization of both Hoxd-11 and Hoxd-10 mRNA expression domains in the prevertebral column and an anterior shift of the lumbosacral transition, demonstrating shared regulatory control of neighboring Hoxd genes by a single cis-element. Targeted mutagenesis in ES cells/transgenic mice; in situ hybridization; gel retardation assays for nuclear receptor binding to region IX Genes & development High 8824591
1999 Double targeted disruption of Hoxd9 and Hoxd10 in mice produces locomotor, skeletal (axial and appendicular), hindlimb peripheral nerve, and distal hindlimb muscle defects more severe than either single mutant, establishing functional cooperativity/genetic interaction between adjacent 5' HoxD genes in patterning the same posterior regions. Gene targeting double-mutant mice; behavioral, skeletal, and neural analysis Developmental biology High 10642795
2001 Simultaneous inactivation of Hoxa10 and Hoxd10 produces more severe hindlimb skeletal and peripheral nervous system defects (including truncations/deletions of tibial and peroneal nerves) than either single mutant, establishing that these paralogous genes coordinately regulate hindlimb skeletal and neural patterning. Double-mutant mouse genetic epistasis; skeletal and neural histological analysis; behavioral locomotor assays Developmental biology High 11180954
2004 Ectopic expression of Hoxd10 in thoracic spinal segments of chick embryos via in ovo electroporation induces motoneurons with a lumbosacral molecular profile (Lim1 and RALDH2 expression) and novel axon projections to hindlimb muscles, demonstrating that Hoxd10 is sufficient to specify lumbosacral motoneuron identity. In ovo electroporation of chick thoracic spinal cord; immunohistochemistry for regional motoneuron markers (Lim1, RALDH2); axon tracing Developmental dynamics High 15305286
2004 cDNA microarray analysis of Hoxd10 single and Hoxa10/Hoxd10 double knockout mouse spinal cords identified 69 downstream target genes with altered expression, including genes involved in cellular communication, cell cycle control, development, and neuronal survival; putative promoter analysis suggested some are direct Hoxd10 targets. cDNA microarray; RT-PCR validation; in situ hybridization; bioinformatic promoter analysis for Hox binding sites in Hoxd10 KO and Hoxa10/Hoxd10 double-KO spinal cord Journal of neuroscience research Medium 14743444
2005 HOXD10, in complex with PBX1b and PREP1 (as HOXD10·PBX1b·PREP1), activates the rat renin promoter; this activation is cooperative with Ets-1 and the intracellular domain of Notch1, establishing renin as a transcriptional target of HOXD10-containing complexes. EMSA; transient transfection reporter assays in COS-7, Calu-6, and As4.1 cells; cotransfection of HOXD10·PBX1b·PREP1, Ets-1, and Notch1-ICD constructs; promoter mutation analysis The Journal of biological chemistry High 15792957
2009 Overexpression of Hoxd10 in the embryonic chick lumbosacral (LS) cord defines the position of the lateral motor column (LMC) and promotes development of lateral LMC (LMCl) motoneurons in rostral LS segments; Hoxd11 suppresses Hoxd10 expression and RALDH2 levels, suggesting Hoxd11 modulates Hoxd10 activity and local retinoic acid to define caudal LMC boundaries. In ovo electroporation overexpression in chick; Hoxd10 loss-of-function mouse analysis; immunohistochemistry for LMC motoneuron markers and RALDH2 Developmental biology High 19306865
2011 miR-10b directly targets the 3'UTR of HOXD10, reducing its translation; downregulation of HOXD10 by miR-10b in glioma cells leads to upregulation of invasion factors MMP-14 and uPAR, promoting glioma cell invasion. Treatment with miR-10b inhibitors restores HOXD10 and reduces invasiveness. miR-10b overexpression/inhibition; Western blot for HOXD10, MMP-14, uPAR; Matrigel invasion assay; antisense oligonucleotide inhibition in glioma cell lines Brain research Medium 21419107
2012 miR-10b promotes gastric cancer cell invasion by targeting HOXD10 (confirmed by translational inhibition); downregulation of HOXD10 by miR-10b leads to increased RhoC expression and AKT phosphorylation. Knockdown of RhoC or inhibition of AKT abolished miR-10b-induced invasion, placing HOXD10 upstream of the RhoC-AKT signaling axis. miR-10b overexpression/inhibition; HOXD10 rescue expression; Transwell invasion assay; RhoC knockdown; AKT inhibition; Western blot in gastric cancer cell lines International journal of oncology High 22293682
2012 TBX1 physically interacts with HOXD10 as determined by co-immunoprecipitation and mass spectrometry; TBX1 and HOXD10 have overlapping expression during murine kidney development, and RNAi-mediated knockdown of TBX1 in HEK293 cells alters TGF-β/BMP signaling, a pathway influenced through TBX1-HOXD10 interaction. Co-immunoprecipitation, mass spectrometry, Western blot, RT-PCR, RNAi in HEK293 cells Gene Medium 22842189
2013 miR-10b promotes nucleus pulposus cell proliferation by directly targeting HOXD10, leading to derepression of the RhoC-Akt pathway; restored HOXD10 expression reversed the mitogenic effect of miR-10b, and knockdown of RhoC or Akt inhibition abolished miR-10b-driven proliferation. miR-10b overexpression; HOXD10 rescue; RhoC knockdown; Akt inhibition; cell proliferation assays; Western blot in nucleus pulposus cells PloS one High 24376640
2013 miR-10b overexpression in ovarian cancer cells decreases HOXD10 protein expression and upregulates MMP14 and RHOC, enhancing migration and invasion; inverse correlation between HOXD10 and MMP14 protein expression was confirmed in patient tumor samples, establishing HOXD10 as a transcriptional repressor of MMP14 and RHOC in ovarian cancer. miR-10b overexpression; Western blot for HOXD10, MMP14, RHOC; migration/invasion assays; immunohistochemistry in patient samples International journal of oncology Medium 23670532
2014 HOXD10 knockdown in HNSCC cells decreases proliferation and invasion; HOXD10 overexpression decreases cell invasion but increases proliferation, adhesion, and migration. Microarray and reporter assays identified angiomotin (AMOT-p80) and miR-146a as direct HOXD10 transcriptional targets; AMOT-p80 manipulation phenocopies HOXD10 manipulation. Stable transfection/siRNA knockdown in HNSCC cells; MTS/migration/adhesion/invasion assays; expression microarray; luciferase reporter assay for AMOT-p80 and miR-146a British journal of cancer High 25010866
2014 POU2F1 transcriptionally regulates HOXD10 and HOXD11 expression in HNSCC; POU2F1 consensus binding sites in the 5' region of HOXD10 are required for optimal promoter activity as confirmed by luciferase reporter constructs; POU2F1 knockdown reduces HOXD10/D11 expression and inhibits HNSCC proliferation. Promoter luciferase reporter assays; POU2F1 siRNA knockdown; qRT-PCR; Western blot in HNSCC cells Oncotarget High 25301728
2014 HOXD10 knockdown in murine uterus reduces implantation rates and correlates with increased EMX2 and IGFBP1 expression and decreased integrin β3 and LIF expression, establishing HOXD10 as a regulator of endometrial receptivity acting through known HOX target genes. shRNA knockdown in mouse uterus via uterine horn injection; qRT-PCR and Western blot; litter size counting at day 9 of pregnancy Human reproduction (Oxford, England) Medium 24549215
2015 HOXD10 acts as a tumor suppressor in cholangiocellular carcinoma (CCC) by inhibiting cell invasion through downregulation of MMP2 and MMP9, inducing G1 cell cycle arrest and apoptosis, and inactivating the RHOC/AKT/MAPK signaling pathway upon overexpression. Lentiviral HOXD10 overexpression in CCC cell lines; invasion assay; flow cytometry for apoptosis/cell cycle; Western blot for RHOC, MMP2, MMP9, AKT, MAPK Oncology reports Medium 26260613
2016 HOXD10 is specifically activated in lymphatic endothelial cells (LECs) at early time points after VEGFR-3 stimulation, and regulates expression of immediate early transcription factors including NR4A1; gain- and loss-of-function of HOXD10 in LECs affects migration, cord-like structure formation, and expression of VE-cadherin, claudin-5, and eNOS, promoting lymphatic endothelial permeability. DeepCAGE transcriptomics; transcription factor activity analysis; gain- and loss-of-function experiments in human LECs; migration assays; tube formation assays; Western blot Journal of cell science Medium 27199372
2017 HOXD10 expression in hepatocellular carcinoma is regulated by promoter region methylation; HOXD10 suppresses HCC cell growth in vitro and in vivo by inhibiting ERK signaling, as demonstrated by HOXD10 overexpression reducing ERK pathway activation. Methylation-specific PCR; 5-Aza-dC demethylation treatment; siRNA/overexpression in HCC cell lines; chromatin immunoprecipitation; flow cytometry; Western blot for ERK; xenograft mouse model Clinical epigenetics Medium 29075359
2018 miR-23a directly targets HOXD10 (validated by luciferase reporter assay); miR-23a overexpression in glioblastoma induces expression of uPAR, RhoA, RhoC, and glial-mesenchymal transition markers (Snail, Slug, MMP2, MMP9, MMP14, E-cadherin changes), and promotes invasion with polarized focal adhesion formation; all these effects are reversed by HOXD10 overexpression. Luciferase reporter assay; miR-23a overexpression; HOXD10 overexpression rescue; Matrigel invasion assay; immunofluorescence for focal adhesions; Western blot in 6 glioblastoma cell lines Signal transduction and targeted therapy High 30603114
2019 HOXD10 suppresses colon cancer cell proliferation, migration, invasion and promotes apoptosis; overexpression of HOXD10 downregulates RHOC and inactivates AKT and MAPK pathways, establishing HOXD10 as a transcriptional regulator upstream of the RHOC/AKT/MAPK axis in colon cancer. HOXD10 expression vector transfection and 5-Aza-dC treatment; MTT, Transwell, wound healing, flow cytometry assays; RT-PCR and Western blot for RHOC, AKT, MAPK in colon cancer cell lines; immunohistochemistry Cell communication and signaling : CCS Medium 30683109
2020 Hoxd10 is required for secretory activation in lactation; targeted disruption of Hoxd10 leads to reduced prolactin receptor expression, reduced STAT5 phosphorylation, decreased milk protein expression, mislocalized GLUT1, increased STAT3 phosphorylation, and leukocyte recruitment in affected mammary gland regions. Transplantation experiments reveal Hoxd10 primarily exerts systemic functions that confer attenuated STAT5 phosphorylation. Hoxd10 KO mice (single and Hoxd9/d10 double); mammary gland transplantation; Western blot for STAT5/STAT3 phosphorylation, prolactin receptor, milk proteins; immunofluorescence for GLUT1; histology Journal of mammary gland biology and neoplasia High 32705545
2021 HOXD10 overexpression in colorectal cancer cells activates transcription of miR-7 and IGFBP3 in a promoter-dependent manner; demethylation studies showed that DNMT1, DNMT3B, and MeCP2 are recruited to the HOXD10 promoter to silence it. HOXD10 restoration enhances 5-FU chemosensitivity in resistant CRC cells. Pyrosequencing; 5-Aza-CdR demethylation; MeCP2 knockdown; luciferase reporter assays; ChIP for DNMT1/DNMT3B/MeCP2 at HOXD10 promoter; cell proliferation/invasion assays; drug resistance assays Frontiers in oncology Medium 34790580
2024 HOXD10 directly binds the NOX4 promoter to repress NOX4 transcription, thereby inhibiting ferroptosis pathway activation and oxidative stress in renal tubular cells. AAV-mediated HOXD10 overexpression attenuates renal fibrosis in UUO mice; HOXD10 hypermethylation silences its expression in TGF-β1-treated cells. ChIP assay and dual-luciferase reporter assay for HOXD10-NOX4 promoter binding; bisulfite sequencing PCR for HOXD10 methylation; AAV-HOXD10 in UUO mice; cellular ferroptosis/oxidative stress markers (ROS, lipid ROS, MDA, GSH/GSSG, SOD) in HK-2 cells Cell death & disease High 38844470
2024 The GABPA transcription factor binds directly to the HOXD10 promoter to regulate its transcription; miR-450b-5p targets GABPA directly, leading to reduced HOXD10 expression and promotion of ectopic endometriotic lesion growth. Intraperitoneal lentiviral HOXD10 overexpression attenuates ectopic lesions in a mouse model. Dual-luciferase reporter assay for GABPA-HOXD10 promoter binding; miR-450b-5p overexpression/knockdown; HOXD10 lentiviral overexpression in vivo; in vitro and in vivo proliferation/invasion/apoptosis assays iScience Medium 39759007
2025 A missense variant HOXD10 p.S80R (in the homeodomain) causes conformational alterations in the protein (larger radius of gyration, fewer hydrogen bonds, expanded solvent-accessible surface area); RNA sequencing revealed that the inhibition of HOXD10 wild-type on IFIT1, IFIT2, and IFIT3 transcription is abrogated by the S80R variant, identifying these interferon-stimulated genes as transcriptional targets of HOXD10. Molecular dynamics simulation; RNA sequencing of cells expressing WT vs. S80R variant HOXD10; WES in MDA patient cohort European journal of obstetrics, gynecology, and reproductive biology Medium 39987682

Source papers

Stage 0 corpus · 92 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1991 Expression of the homeobox Hox-4 genes and the specification of position in chick wing development. Nature 361 1673231
1992 Targeted misexpression of Hox-4.6 in the avian limb bud causes apparent homeotic transformations. Nature 279 1352858
1991 HOX-4 genes and the morphogenesis of mammalian genitalia. Genes & development 244 1680771
1993 Mice homozygous for a targeted disruption of Hoxd-3 (Hox-4.1) exhibit anterior transformations of the first and second cervical vertebrae, the atlas and the axis. Development (Cambridge, England) 199 7910549
1990 Human Hox-4.2 and Drosophila deformed encode similar regulatory specificities in Drosophila embryos and larvae. Cell 190 1979526
2013 MicroRNA-10b promotes nucleus pulposus cell proliferation through RhoC-Akt pathway by targeting HOXD10 in intervetebral disc degeneration. PloS one 164 24376640
2011 MicroRNA-10b induces glioma cell invasion by modulating MMP-14 and uPAR expression via HOXD10. Brain research 156 21419107
1991 HOX4 genes encode transcription factors with potential auto- and cross-regulatory capacities. The EMBO journal 126 1756725
1991 The Hox-4.8 gene is localized at the 5' extremity of the Hox-4 complex and is expressed in the most posterior parts of the body during development. Mechanisms of development 125 1685889
1993 Identification of a retinoic acid response element upstream of the murine Hox-4.2 gene. Molecular and cellular biology 123 8093325
2012 miR-10b promotes cell invasion through RhoC-AKT signaling pathway by targeting HOXD10 in gastric cancer. International journal of oncology 121 22293682
2014 MicroRNA-10b promotes migration and invasion through KLF4 and HOXD10 in human bladder cancer. Oncology reports 97 24573354
1992 An autoregulatory element of the murine Hox-4.2 gene. The EMBO journal 96 1356763
1997 Targeted disruption of Hoxd-10 affects mouse hindlimb development. Development (Cambridge, England) 95 9409668
2013 Loss of HOXD10 expression induced by upregulation of miR-10b accelerates the migration and invasion activities of ovarian cancer cells. International journal of oncology 91 23670532
1996 In vivo targeted mutagenesis of a regulatory element required for positioning the Hoxd-11 and Hoxd-10 expression boundaries. Genes & development 85 8824591
1991 EVX2, a human homeobox gene homologous to the even-skipped segmentation gene, is localized at the 5' end of HOX4 locus on chromosome 2. Genomics 79 1675198
1993 Analysis of Hox-4.5 and Hox-3.6 expression during newt limb regeneration: differential regulation of paralogous Hox genes suggest different roles for members of different Hox clusters. Development (Cambridge, England) 76 8104776
1990 Primary structure and embryonic expression pattern of the mouse Hox-4.3 homeobox gene. Development (Cambridge, England) 72 1982431
2014 Regulation of endometrial receptivity by the highly expressed HOXA9, HOXA11 and HOXD10 HOX-class homeobox genes. Human reproduction (Oxford, England) 65 24549215
1992 Comparison of mouse and human HOX-4 complexes defines conserved sequences involved in the regulation of Hox-4.4. The EMBO journal 63 1348690
2001 The paralogous Hox genes Hoxa10 and Hoxd10 interact to pattern the mouse hindlimb peripheral nervous system and skeleton. Developmental biology 62 11180954
1994 Insertion of a targeting construct in a Hoxd-10 allele can influence the control of Hoxd-9 expression. Developmental dynamics : an official publication of the American Association of Anatomists 60 7894075
1999 Targeted disruption of Hoxd9 and Hoxd10 alters locomotor behavior, vertebral identity, and peripheral nervous system development. Developmental biology 56 10642795
2018 miR-23a promotes invasion of glioblastoma via HOXD10-regulated glial-mesenchymal transition. Signal transduction and targeted therapy 54 30603114
2004 Ectopic expression of Hoxd10 in thoracic spinal segments induces motoneurons with a lumbosacral molecular profile and axon projections to the limb. Developmental dynamics : an official publication of the American Association of Anatomists 51 15305286
2014 The roles of HOXD10 in the development and progression of head and neck squamous cell carcinoma (HNSCC). British journal of cancer 48 25010866
2013 Targeting microRNA-23a to inhibit glioma cell invasion via HOXD10. Scientific reports 46 24305689
1992 Expression of Hox-4 genes in the chick wing links pattern formation to the epithelial-mesenchymal interactions that mediate growth. The EMBO journal 46 1348689
2014 POU2F1 activity regulates HOXD10 and HOXD11 promoting a proliferative and invasive phenotype in head and neck cancer. Oncotarget 44 25301728
2006 HOXD10 M319K mutation in a family with isolated congenital vertical talus. Journal of orthopaedic research : official publication of the Orthopaedic Research Society 40 16450407
1996 Evolutionary analyses of hedgehog and Hoxd-10 genes in fish species closely related to the zebrafish. Proceedings of the National Academy of Sciences of the United States of America 39 8917540
2019 Epigenetic inactivation of HOXD10 is associated with human colon cancer via inhibiting the RHOC/AKT/MAPK signaling pathway. Cell communication and signaling : CCS 38 30683109
2017 Silencing HOXD10 by promoter region hypermethylation activates ERK signaling in hepatocellular carcinoma. Clinical epigenetics 38 29075359
2015 HOXD10 acts as a tumor-suppressive factor via inhibition of the RHOC/AKT/MAPK pathway in human cholangiocellular carcinoma. Oncology reports 38 26260613
1992 Isolation and analysis of embryonic expression of Hox-4.9, a member of the murine labial-like gene family. Mechanisms of development 38 1356009
2015 MicroRNA-10b promotes migration and invasion through Hoxd10 in human gastric cancer. World journal of surgical oncology 37 26311318
2016 miR-10b promotes invasion by targeting HOXD10 in colorectal cancer. Oncology letters 36 27347170
2001 Hoxd10 induction and regionalization in the developing lumbosacral spinal cord. Development (Cambridge, England) 35 11493545
2004 Identification of a Hoxd10-regulated transcriptional network and combinatorial interactions with Hoxa10 during spinal cord development. Journal of neuroscience research 33 14743444
2017 Combined Detection of Plasma ZIC1, HOXD10 and RUNX3 Methylation is a Promising Strategy for Early Detection of Gastric Cancer and Precancerous Lesions. Journal of Cancer 32 28529617
2005 Activation of the rat renin promoter by HOXD10.PBX1b.PREP1, Ets-1, and the intracellular domain of notch. The Journal of biological chemistry 32 15792957
1994 A proline-rich transcriptional activation domain in murine HOXD-4 (HOX-4.2). Nucleic acids research 32 7907418
1992 The mis-expression of posterior Hox-4 genes in talpid (ta3) mutant wings correlates with the absence of anteroposterior polarity. Development (Cambridge, England) 32 1352242
2018 miR-224 enhances invasion and metastasis by targeting HOXD10 in non-small cell lung cancer cells. Oncology letters 29 29731873
2024 HOXD10 attenuates renal fibrosis by inhibiting NOX4-induced ferroptosis. Cell death & disease 27 38844470
1998 Expression of HOXD10 gene in normal endometrium and endometrial adenocarcinoma. Journal of the Society for Gynecologic Investigation 26 9773404
2021 MiR-501 promotes tumor proliferation and metastasis by targeting HOXD10 in endometrial cancer. Cellular & molecular biology letters 24 34022794
1990 The murine genes Hox-5.1 and Hox-4.1 belong to the same HOX complex on chromosome 2. Genomics 23 1973141
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