Affinage

HOXC8

Homeobox protein Hox-C8 · UniProt P31273

Length
242 aa
Mass
27.8 kDa
Annotated
2026-06-10
100 papers in source corpus 39 papers cited in narrative 39 extracted findings
Cross-family judge vs UniProt: tie faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

HOXC8 is a homeodomain transcription factor that directs anteroposterior patterning of the developing skeleton and nervous system and is repeatedly redeployed as a driver of cancer and fibrosis (PMID:8103190, PMID:9707582, PMID:15753214). It binds DNA at Hox core and Hox-Pbx consensus sites in native chromatin to either activate or repress target promoters, regulating genes governing cell adhesion, proliferation, oncogenesis, and apoptosis (PMID:8103190, PMID:15699330, PMID:16793922, PMID:20097160). In development, HOXC8 controls progression of chondrocytes through differentiation in a dosage-dependent manner (PMID:9707582, PMID:19071237) and acts downstream of retinaldehyde/RA signaling to specify and maintain terminal differentiation of brachial spinal motor neurons, with sustained activity required postnatally (PMID:15753214, PMID:35315772). Its developmental expression is established and bounded by a modular early enhancer whose combinatorial cis-elements direct distinct neural tube, somite, and lateral plate mesoderm domains (PMID:8575334, PMID:8901587, PMID:8637890); this enhancer integrates Cdx1 and Gdf11/Smad3 inputs that time and position HOXC8 activation (PMID:22426122, PMID:28695962). HOXC8 partners directly with Smad1 through its homeodomain to control BMP-responsive osteogenic transcription (PMID:10625647), and forms complexes with Pbx1, ILF3, DLX5, and HDAC1/2 to specify target selection and activity (PMID:16637071, PMID:29296180, PMID:32631410, PMID:40701951). In cancer, HOXC8 activates CDH11 to engage a CDH11–Trio–Rac migration axis and drive invasion and metastasis (PMID:22593800, PMID:24810778), suppresses pyroptosis by recruiting HDAC1/2 to repress CASP1 (PMID:40701951), and acts upstream of TGFβ1/Smad signaling; in hepatic stellate cells and renal fibroblasts it establishes a TGFβ1–Smad positive-feedback loop and recruits the P-TEFb elongation complex to drive fibrotic gene programs (PMID:29367650, PMID:37099809, PMID:41476080, PMID:32877504). The HOXC8 locus is itself a node of epigenetic control, activated by Ap2δ-recruited menin/MLL2-Ash2L H3K4 methyltransferase activity and silenced by Lsh-dependent DNA methylation that stalls RNA Pol II (PMID:14992727, PMID:18495928, PMID:20161795); post-transcriptionally, miR-196 family members target its 3'UTR to limit HOXC8 protein and its migratory output (PMID:20736365, PMID:21077158).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 1993 Medium

    Established that Hoxc8 protein occupies specific DNA sequences in living chromatin and regulates downstream target genes, defining it as a sequence-specific transcriptional regulator rather than merely a patterning marker.

    Evidence Immunopurification of Hoxc8-bound DNA from native chromatin in mouse

    PMID:8103190

    Open questions at the time
    • Direct binding motif not yet defined
    • Activation versus repression at targets not resolved
    • Single method, single lab
  2. 1996 High

    Resolved how spatial and temporal HOXC8 expression is encoded, showing combinatorial cis-regulatory elements in an early enhancer plus long-range downstream elements partition expression into tissue-specific domains.

    Evidence Systematic cis-element mutagenesis in transgenic mouse reporters and large genomic fragment analysis

    PMID:8575334 PMID:8637890 PMID:8901587

    Open questions at the time
    • Trans-acting factors binding each element not identified at this stage
    • Mechanism of element interdependence unknown
  3. 1998 High

    Demonstrated that HOXC8 dosage controls chondrocyte differentiation progression, linking the patterning factor to a concrete cellular differentiation phenotype.

    Evidence Transgenic mouse overexpression with cartilage histology, compared against other Hox transgenes

    PMID:9707582

    Open questions at the time
    • Direct chondrocyte target genes not identified
    • Molecular mechanism of maturation arrest unresolved
  4. 2000 High

    Identified a direct physical link between HOXC8 and BMP signaling, showing Smad1 binds the homeodomain to control osteogenic transcription and bone matrix formation.

    Evidence Yeast two-hybrid, EMSA, deletion mapping, and differentiation/mineralization assays in 2T3 cells

    PMID:10625647

    Open questions at the time
    • Genome-wide Smad1–Hoxc8 co-targets not mapped
    • Whether interaction is activating or repressive context-dependent
  5. 2006 High

    Provided genome-scale direct target identification, defining a HOXC8 consensus and a cohort of bound, regulated genes (e.g., OPN, Fzd2) implicated in adhesion, proliferation, and apoptosis.

    Evidence Expression microarray combined with high-throughput ChIP for endogenous Hoxc8

    PMID:15699330 PMID:16793922

    Open questions at the time
    • Cell-type dependence of target repertoire not addressed
    • Co-factor requirements at each site not defined
  6. 2006 Medium

    Showed HOXC8 cooperates with the Pbx1 co-factor in a heterocomplex to sustain androgen-independent prostate cancer growth, framing HOXC8 as a context-dependent oncogenic regulator.

    Evidence Co-IP and siRNA double knockdown with proliferation readouts in DU145 cells

    PMID:16637071

    Open questions at the time
    • Direct co-bound target genes not identified
    • Two methods, single lab
  7. 2008 High

    Defined epigenetic activation of the Hoxc8 locus by H3K4 methyltransferase complexes, showing Ap2δ recruits Ash2l/MLL2 to deposit H3K4me3 and drive transcription, building on the earlier menin–MLL2 link.

    Evidence Yeast two-hybrid, Co-IP, locus ChIP for Ash2l/Alr and H3K4me3, transactivation assay

    PMID:14992727 PMID:18495928

    Open questions at the time
    • Signals controlling Ap2δ recruitment unknown
    • Relationship to repressive marks not integrated
  8. 2010 High

    Revealed a silencing mechanism in which Lsh-dependent CpG methylation at the locus stalls RNA Pol II elongation rather than blocking recruitment, identifying elongation control as a key regulatory layer.

    Evidence Lsh knockout cells with methylation analysis, Pol II ChIP, nucleosome mapping, and Chd1 assays

    PMID:20161795

    Open questions at the time
    • Trigger for Lsh-mediated methylation not defined
    • Interplay with activating H3K4 machinery unresolved
  9. 2010 High

    Established post-transcriptional control of HOXC8 by miR-196 family targeting of its 3'UTR, placing HOXC8 downstream of a microRNA axis governing cancer cell migration and metastasis.

    Evidence 3'UTR luciferase reporters, miRNA overexpression, in vitro/in vivo metastasis with HOXC8 rescue

    PMID:20736365 PMID:21077158

    Open questions at the time
    • Relative contribution of individual miR-196 family members unclear
    • Upstream regulation of miR-196 not addressed
  10. 2010 High

    Showed HOXC8 antagonizes nuclear receptor coactivation, blocking AR-dependent SRC-3/CBP recruitment and histone acetylation, demonstrating it can act by sequestering coactivators.

    Evidence ChIP at the PSA enhancer, Co-IP, and SRC-3 overexpression rescue in prostate cancer cells

    PMID:21047772

    Open questions at the time
    • Generality across other nuclear receptors not tested
    • Structural basis of AR–SRC-3 disruption unknown
  11. 2011 High

    Connected HOXC8 to a defined cytoskeletal signaling axis, showing it drives CDH11 expression to enable Trio-dependent Rac activation and membrane ruffling in migrating breast cancer cells.

    Evidence siRNA, Co-IP (CDH11–Trio), Rac activity assays, active-Rac1 rescue, and imaging

    PMID:22593800

    Open questions at the time
    • Whether HOXC8 binds CDH11 directly resolved only later
    • In vivo relevance of the Trio–Rac axis not tested here
  12. 2014 High

    Confirmed direct, site-specific HOXC8 activation of the CDH11 promoter and established epistasis, with CDH11 re-expression rescuing migration, invasion, and metastasis defects.

    Evidence ChIP, site-mapped luciferase assays, siRNA, CDH11 rescue, soft-agar and invasion assays

    PMID:24810778

    Open questions at the time
    • Co-factors at the CDH11 promoter defined only in later work
    • Determinants of activation versus repression at different targets unclear
  13. 2018 Medium

    Identified TGFβ1 as a direct HOXC8 transcriptional target mediating proliferation, anchorage independence, migration, and chemoresistance, linking HOXC8 to TGFβ-driven malignancy.

    Evidence ChIP, luciferase, knockdown/overexpression, and TGFβ1-blocking rescue in NSCLC cells

    PMID:29367650

    Open questions at the time
    • Feedback architecture established only in later fibrosis studies
    • Single lung cancer context
  14. 2022 High

    Demonstrated that HOXC8 is required continuously, not just transiently, to maintain motor neuron terminal differentiation, redefining it as a sustained identity factor rather than an initiation-only switch.

    Evidence Stage-specific conditional Hoxc8 knockout, brachial MN transcriptomics, behavior, and in vitro gain-of-function

    PMID:35315772

    Open questions at the time
    • Direct terminal differentiation target genes not exhaustively mapped
    • Maintenance co-factors not identified
  15. 2025 High

    Mechanistically unified HOXC8 as a pro-fibrotic master regulator that establishes a TGFβ1–Smad self-reinforcing loop and recruits the P-TEFb elongation complex to drive fibrotic transcription in liver and kidney.

    Evidence Conditional/fibroblast-specific knockouts, CCl4 and renal fibrosis models, phospho-Smad and cistromic/histone analyses

    PMID:32877504 PMID:37099809 PMID:41476080

    Open questions at the time
    • Direct mechanism of P-TEFb recruitment to the HOXC8 cistrome not structurally defined
    • How fibrotic and developmental target programs are partitioned unknown
  16. 2025 High

    Extended HOXC8 repressive output to programmed cell death, showing it recruits HDAC1/2 to silence CASP1 and suppress pyroptosis, demonstrating a chromatin-modifier-based repression mechanism.

    Evidence Co-IP (HOXC8–HDAC1), ChIP for HOXC8/HDAC1 at the CASP1 promoter, rescue experiments, and in vivo siRNA in NSCLC

    PMID:40701951

    Open questions at the time
    • Determinants directing HDAC recruitment to specific promoters unknown
    • Generality of pyroptosis suppression beyond NSCLC untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved what molecular logic dictates whether HOXC8 activates or represses a given target and how its developmental versus pro-fibrotic/oncogenic cistromes are selected across cell types.
  • No unified model of activator-versus-repressor switching
  • Cell-type-specific cistrome determinants not defined
  • Structural basis of partner-directed target selection unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 10 GO:0003677 DNA binding 6 GO:0098772 molecular function regulator activity 3
Localization
GO:0005634 nucleus 4
Pathway
R-HSA-74160 Gene expression (Transcription) 7 R-HSA-1266738 Developmental Biology 5 R-HSA-162582 Signal Transduction 5 R-HSA-4839726 Chromatin organization 4
Partners
DLX5HDAC1ILF3NCOA3PBX1SMAD1TRIO
Complex memberships
P-TEFb (recruited)

Evidence

Reading pass · 39 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2004 Menin associates with a trithorax-family histone methyltransferase complex containing MLL2 and Ash2L that methylates histone H3 on lysine 4; menin is bound to the Hoxc8 locus by chromatin immunoprecipitation, and Men1 knockout cells show decreased Hoxc8 expression. Co-immunoprecipitation, histone methyltransferase activity assay, chromatin immunoprecipitation (ChIP), Men1 knockout mouse/cell analysis Molecular cell High 14992727
2000 Smad1 physically interacts with Hoxc8 through two regions within its amino-terminal 87 amino acids; one of these regions binds the Hoxc8 homeodomain. Overexpression of these Smad1 interaction domains activates osteopontin transcription and induces osteoblast differentiation and mineralized bone matrix formation in 2T3 cells. Yeast two-hybrid, gel-shift (EMSA), deletion analysis, transient and stable transfection assays, alkaline phosphatase/mineralization readouts The Journal of biological chemistry High 10625647
1993 Hoxc8 protein binds DNA sequences in native chromatin and regulates expression of target genes including the mouse homologue of the Drosophila tumour-suppressor gene l(2)gl, identified by immunopurification of chromatin-bound DNA. Immunopurification of DNA bound to Hoxc8 in native chromatin (chromatin-IP precursor approach) Nature Medium 8103190
1998 Overexpression of a Hoxc8 transgene in mice causes cartilage defects characterized by accumulation of proliferating chondrocytes and reduced maturation, demonstrating that Hoxc8 controls the progression of cells along the chondrocyte differentiation pathway in a dosage-dependent and Hox-class-specific manner. Transgenic mouse overexpression with skeletal histological and cartilage-maturation phenotypic analysis; comparison with Hoxd4 and Isl-1 transgenics Proceedings of the National Academy of Sciences of the United States of America High 9707582
2005 Hoxc8 directly binds the osteopontin (OPN/Spp1) promoter in vivo (confirmed by ChIP), repressing its expression ~4.8-fold; Hoxc8 also directly binds regulatory regions of five other genes (including Fzd2) involved in oncogenesis, cell adhesion, proliferation, and apoptosis. Mouse oligonucleotide microarray (16,463 genes), chromatin immunoprecipitation (ChIP) of endogenous Hoxc8 at target gene promoters Proceedings of the National Academy of Sciences of the United States of America High 15699330
1995 A 135 bp early neural tube (ENT) enhancer located ~3 kb upstream of Hoxc8 directs posterior neural tube expression via four interdependent combinatorial elements (A–D); element A is essential but requires interaction with at least two of B, C, or D for activity. Deletion analysis and nucleotide substitution mutagenesis in transgenic mouse reporter assays Development (Cambridge, England) High 8575334
1996 A fifth cis-acting element (E) in the Hoxc8 early enhancer directs mesoderm expression in combination with elements A–D; different element combinations determine tissue-specific expression (neural tube: ABC/ABD/ACD; somite: ACDE; lateral plate mesoderm: DE), and mutations cause posteriorization of reporter expression. Transgenic mouse reporter assay with systematic cis-element mutation combinations Proceedings of the National Academy of Sciences of the United States of America High 8901587
1996 Regulatory elements that maintain the anterior boundaries of Hoxc8 expression in neural tube and paraxial mesoderm at later developmental stages are located 11–19 kb downstream of the Hoxc8 gene, demonstrating that long-range cis-regulatory elements govern the late phase of Hoxc8 expression. Yeast homologous recombination (pClasper vector) to clone 27 kb genomic region; reporter transgene analysis in transgenic mice Proceedings of the National Academy of Sciences of the United States of America Medium 8637890
1998 Differences in cis-regulatory sequences of the Hoxc8 early enhancer between chicken and mouse cause a temporal delay in Hoxc8 activation in chicken, restricting its paraxial mesoderm expression to a more posterior domain; transgenic mouse assays show the chicken enhancer directs more posterior reporter expression than the mouse enhancer. Comparative sequence analysis; transgenic mouse reporter assays with chicken and mouse Hoxc8 early enhancer constructs Proceedings of the National Academy of Sciences of the United States of America Medium 9482889
2006 Chromatin immunoprecipitation combined with microarray and high-throughput ChIP identified five direct Hoxc8 target genes (including OPN and Fzd2) out of 34 responsive genes; all five contain Hoxc8 consensus binding sites and encode proteins involved in oncogenesis, cell adhesion, proliferation, and apoptosis. Microarray expression profiling, genome-wide Hoxc8 DNA-binding site analysis, high-throughput ChIP Proceedings of the National Academy of Sciences of the United States of America High 16793922
2008 Transcription factor Ap2delta associates with Ash2l and the MLL family histone methyltransferase ALR/MLL2 in a complex that trimethylates H3K4; Ap2delta is required for recruitment of this complex to the Hoxc8 locus, leading to H3K4me3 and Hoxc8 transcriptional activation. Yeast two-hybrid screen, co-immunoprecipitation, ChIP for Ash2l/Alr and H3K4me3 at Hoxc8 locus, dose-dependent transactivation assay Proceedings of the National Academy of Sciences of the United States of America High 18495928
2010 Lsh controls CpG methylation at the Hoxc8 locus; in wild-type cells, DNA methylation at Hoxc8 is associated with RNA Pol II stalling (not failure to bind) as the silencing mechanism. In Lsh-/- cells, hypomethylation at Hoxc8 permits efficient Pol II transcriptional elongation facilitated by the chromodomain protein Chd1. Lsh knockout mouse cells, DNA methylation analysis, Pol II ChIP, nucleosomal mapping, Chd1 functional assays PloS one High 20161795
2010 HOXC8 inhibits androgen receptor (AR)-mediated transcriptional induction in prostate cancer cells by blocking hormone-dependent recruitment of the coactivator SRC-3 and CBP to androgen-regulated gene enhancers, inhibiting histone acetylation; forced SRC-3 expression reverses HOXC8-mediated inhibition, and co-immunoprecipitation shows HOXC8 disrupts the AR–SRC-3 interaction. Transient transfection, ChIP for SRC-3/CBP/histone acetylation at PSA enhancer, co-immunoprecipitation, SRC-3 rescue experiment Molecular cancer research : MCR High 21047772
2006 Immunoprecipitation of Pbx1 in prostate cancer DU145 cells reveals a Pbx1–HoxC8 heterocomplex; siRNA knockdown of either Pbx1 or HoxC8 suppresses androgen-independent cell growth, and double knockdown suppresses growth more significantly, indicating functional cooperation. Co-immunoprecipitation, siRNA knockdown, cell proliferation assay, DNA microarray The Prostate Medium 16637071
2011 HOXC8 is required for cadherin 11 (CDH11) expression in breast cancer cells; HOXC8 depletion reduces CDH11 levels, actin-based membrane ruffles, and Rac activity; CDH11 interacts physically with Trio (a Rac GEF) and is required for Trio plasma membrane localization and Rac activation, placing HOXC8 upstream of a CDH11–Trio–Rac signaling axis in cell migration. siRNA knockdown, ectopic expression, co-immunoprecipitation (CDH11–Trio), Rac activity assay, active-Rac1 rescue, confocal imaging of membrane ruffles and Trio localization Genes & cancer High 22593800
2014 HOXC8 directly binds the CDH11 promoter at nucleotides -196 to -191 and acts as a transcriptional activator; depletion of HOXC8 reduces anchorage-independent growth, migration/invasion, and metastasis, all of which are rescued by ectopic CDH11 expression. Chromatin immunoprecipitation, luciferase promoter assay, siRNA knockdown, ectopic CDH11 rescue, soft-agar and invasion assays Oncotarget High 24810778
2015 HOXC8 directly binds the embigin (EMB) promoter at nucleotides -2303 to -2315 and acts as a transcriptional repressor; HOXC8 knockdown increases EMB expression, and the pro-tumorigenic effects of HOXC8 knockdown (increased proliferation, migration) are rescued by co-depletion of embigin. Western blot, luciferase reporter gene assay, chromatin immunoprecipitation, siRNA knockdown, epistasis rescue experiments Oncotarget High 26090721
2007 Endogenous Hoxc8 binds directly to the enhancer region of mouse naked cuticle 2 (mNkd2) gene; introduction of exogenous Hoxc8 into NIH3T3 cells reduces mNkd2 mRNA expression, establishing mNkd2 as a direct transcriptional target through which Hoxc8 cross-talks with the Wnt signaling pathway. Chromatin immunoprecipitation (ChIP), electrophoretic mobility shift assay (EMSA), reporter assay, mRNA expression analysis after Hoxc8 overexpression Journal of experimental zoology. Part A, Ecological genetics and physiology High 17094106
2009 Hoxc8 overexpression suppresses basal Smad6 promoter activity and BMP2/Smad1-induced Smad6 transcription; ChIP from mouse embryos shows both Smad1 and Hoxc8 are present at the Smad6 promoter, suggesting Hoxc8 regulates Smad6 indirectly through a complex with Smad1 (no direct Hox binding motif in the Smad6 promoter). Promoter luciferase assay, RT-PCR, chromatin immunoprecipitation with anti-Smad1 and anti-Hoxc8 antibodies in mouse embryos Molecules and cells Medium 20016939
2010 Proliferating cell nuclear antigen (Pcna) is a direct transcriptional target of Hoxc8; Hoxc8 binds Hox core and Hox-Pbx binding sequences in the Pcna upstream regulatory region (confirmed by ChIP in embryos), overexpression of Hoxc8 increases Pcna transcript levels and cell proliferation rate. Chromatin immunoprecipitation in mouse embryos (E11.5), promoter sequence analysis, Hoxc8 overexpression with RT-PCR and proliferation assay Biochemical and biophysical research communications Medium 20097160
2005 Retinaldehyde dehydrogenase 2 (Raldh2) conditional knockout causes loss of Lim1+ brachial motoneurons and Islet1+ neuron mispositioning; the molecular basis involves deregulation of Hoxc8, which regulates RARbeta. Hoxc8 mutant mice exhibit the same motoneuron specification defects (phenocopy), establishing Hoxc8 downstream of Raldh2/RA signaling in brachial motoneuron specification. Conditional knockout (Raldh2 and Hoxc8 null mice), immunofluorescence for motoneuron markers (Lim1, Islet1), molecular phenotype comparison Development (Cambridge, England) High 15753214
2015 LMP1 (EBV) represses HoxC8 expression in nasopharyngeal carcinoma cells via RNA Pol II stalling, partially reversible by irradiation through epigenetic regulator TET3; HoxC8 modulates glycolysis and regulates TCA cycle-related gene expression, and ectopic HoxC8 inhibits NPC cell growth in vitro and in vivo. RNA Pol II ChIP, TET3 manipulation, ectopic HoxC8 expression, glycolysis assays, in vivo xenograft Oncogene Medium 25745994
2018 HOXC8 functions as a transcriptional activator of TGFβ1, and this elevated TGFβ1 mediates HOXC8-driven proliferation, anchorage-independent growth, migration, and chemoresistance in non-small cell lung cancer cells. ChIP, promoter luciferase assay, siRNA knockdown, ectopic overexpression, TGFβ1 blocking rescue experiments, colony formation and migration assays Oncogenesis Medium 29367650
2017 ILF3 physically interacts with HOXC8 (co-immunoprecipitation and mass spectrometry) and they cooperate to activate CDH11 transcription; ILF3 binds CDH11 promoter at specific nucleotide positions and requires HOXC8 for co-activation. Co-immunoprecipitation, mass spectrometry, ChIP, luciferase reporter assay, siRNA knockdown Oncotarget Medium 29296180
2019 HOXC8 directly activates transcription of MGP (matrix Gla protein) by binding its promoter; elevated MGP promotes EMT and drives proliferation and migration specifically in triple-negative breast cancer cells. Chromatin immunoprecipitation, luciferase assay, siRNA knockdown and overexpression, EMT marker analysis Molecular carcinogenesis Medium 31264274
2022 Sustained Hoxc8 activity is required not only to establish but also to maintain terminal differentiation markers in brachial spinal motor neurons postnatally; conditional inactivation of Hoxc8 at successive developmental stages causes motor deficits, and in vitro-generated MNs show Hoxc8 is sufficient to induce terminal differentiation gene expression directly. Conditional Hoxc8 knockout in mice at successive stages, transcriptomics of brachial MNs, motor behavioral assays, in vitro MN generation with Hoxc8 gain/loss-of-function eLife High 35315772
2012 Cdx1 directly binds three pairs of conserved Cdx binding sites in the HoxC8 early enhancer during Xenopus embryogenesis (confirmed by ChIP); Cdx1 overexpression or knockdown causes precocious or delayed HoxC8 expression respectively, establishing Cdx1 as a direct transcriptional activator of HoxC8 expression. Xenopus Cdx1 overexpression and antisense morpholino knockdown, transgenic reporter (mouse HoxC8 early enhancer in Xenopus), ChIP for Cdx1 binding in embryos, Cdx binding site mutagenesis FASEB journal High 22426122
2017 Gdf11/Smad signaling and Cdx proteins synergistically activate the Hoxc8 early enhancer; mutagenesis identified two Smad binding motifs and two Cdx binding motifs as required elements; Gdf11 stimulation is partially inhibited by Specific Inhibitor of Smad3, implicating Smad3 in signal transduction. Luciferase reporter transfection in HepG2 cells, Gdf11/Cdx overexpression, site-directed mutagenesis of enhancer motifs, Smad3 inhibitor The International journal of developmental biology Medium 28695962
2008 The 16 amino acid third helix (residues 191–206) of the Hoxc8 homeodomain is a protein transduction domain (PTD) sufficient for cellular membrane penetration; transduction efficiency increases with PTD copy number. The homeodomain region of Hoxc8 is also required for forming protein–DNA complexes that can be delivered intracellularly. GFP-fusion protein transduction assay in primary pig fibroblasts and COS-7 cells, gel retardation/agarose gel DNA-complex assay, concentration-response and multimer experiments Biochemical and biophysical research communications Medium 18835255
2023 HOXC8 activates TGFβ1 transcription and enhances phosphorylated Smad2/Smad3 levels in hepatic stellate cells, creating a positive feedback loop; knockdown of HOXC8 suppresses TGF-β1-induced HSC activation and fibrotic gene (α-SMA, COL1a1) induction in vitro and alleviates liver fibrosis in a CCl4 mouse model in vivo. HOXC8 overexpression and knockdown in LX-2 cells and CCl4 mouse model, Western blot for phospho-Smad2/3, qPCR for fibrotic genes, luciferase/ChIP implied by context of TGFβ1 activation claim Biochemical and biophysical research communications Medium 37099809
2025 HOXC8 negatively regulates CASP1 (caspase-1) expression by recruiting HDAC1/2 to the CASP1 promoter; HOXC8 and HDAC1 are in the same immunocomplex and HOXC8 is required for HDAC1 recruitment to the CASP1 promoter, suppressing CASP1 transcription and thereby preventing pyroptosis in NSCLC cells. Co-immunoprecipitation (HOXC8–HDAC1), ChIP (HOXC8 and HDAC1 at CASP1 promoter), siRNA knockdown, YVAD/disulfiram rescue of pyroptosis, CASP1 forced expression, cholesterol-conjugated siRNA in vivo Cell death & disease High 40701951
2025 Hoxc8 is a central pro-fibrotic transcription factor downstream of TGF-β–Smad3 signaling in kidney fibrosis; Hoxc8 reinforces its own expression and drives fibrotic gene programs by recruiting the P-TEFb transcriptional elongation complex; fibroblast-specific Hoxc8 deletion protects mice from renal fibrosis. Transcriptomic and cistromic (ChIP-seq implied) analyses, fibroblast-specific conditional Hoxc8 knockout mice, methionine restriction dietary model, histone mark analysis at Hoxc8 locus Nature communications High 41476080
2010 miR-196a/b directly targets the HOXC8 3'UTR (confirmed by luciferase reporter), suppressing HOXC8 protein expression; HOXC8 knockdown suppresses breast cancer cell migration and metastasis, and ectopic HOXC8 expression rescues the anti-migratory effect of miR-196, placing HOXC8 downstream of miR-196 in a migration-regulatory axis. Luciferase 3'UTR reporter assay, siRNA knockdown, lentiviral miRNA overexpression, in vitro invasion, in vivo spontaneous metastasis assay, HOXC8 ectopic rescue Cancer research High 20736365
2011 miR-196a directly interacts with the HOX-C8 3'UTR (confirmed by luciferase assay with different HOX-C8 3'UTR fragments), and stable miR-196a expression down-regulates HOX-C8 in melanoma cells, leading to changes in HOX-C8 target genes cadherin-11, calponin-1, and osteopontin. Luciferase 3'UTR reporter assay with deletion fragments, stable miR-196a transfection, target gene expression analysis International journal of cancer Medium 21077158
2020 DLX5 and HOXC8 form a protein complex and together bind and negatively regulate the LINC01013 lncRNA promoter; co-expression of DLX5 and HOXC8 enhances chondrogenic differentiation of stem cells from apical papilla (SCAPs) in vitro and restores cartilage defect in a rabbit knee model in vivo. Co-immunoprecipitation (DLX5–HOXC8 complex), ChIP at LINC01013 promoter, Western blot, Alcian Blue staining, pellet culture, in vivo rabbit cartilage transplantation Stem cell research & therapy Medium 32631410
2025 HOXC8 in cancer-associated fibroblasts (CAFs) directly binds the GCH1 promoter and activates its transcription (confirmed by dual luciferase reporter and bioinformatics); HOXC8-driven GCH1 upregulation suppresses ferroptosis and promotes lung cancer cell malignant progression; si-HOXC8 in CAFs inhibited tumor growth and GCH1 expression in vivo. Dual luciferase reporter assay, bioinformatics binding analysis, siRNA knockdown, GCH1 overexpression rescue, xenograft tumor model, IHC Pathology, research and practice Medium 41505981
2025 HOXC8 transcriptionally activates TRIM22 expression, leading to ubiquitination and degradation of IκBα and subsequent NF-κB signaling activation; this HOXC8/TRIM22/NF-κB axis drives stemness and chemoresistance in colorectal cancer cells. ChIP for HOXC8 at TRIM22 promoter, IκBα ubiquitination assay, NF-κB pathway reporter, siRNA knockdown and overexpression, stemness/sphere-formation assays Cancer letters Medium 41265630
2020 HOXC8 overexpression in endometrial stromal cells significantly enhances cell proliferation, migration, adhesion, and fibrotic activities, and increases phosphorylated SMAD2/SMAD3 levels; the adhesion and fibrosis activities induced by HOXC8 are blocked by TGF-β receptor type I kinase inhibitor E-616452, placing HOXC8 upstream of TGF-β/SMAD signaling. HOXC8 overexpression in euESCs, cell function assays (proliferation, migration, adhesion, fibrosis), Western blot for phospho-SMAD2/3, pharmacological TGFβRI inhibition The Journal of clinical endocrinology and metabolism Medium 32877504
2008 Morpholino-mediated knockdown of Hoxc8 in primary chondrocytes reduces cell proliferation (decreased PCNA expression and phospho-histone H3) without apoptosis, and causes cells to be delayed in M-phase progression, implicating Hoxc8 in cell cycle control at the M-phase checkpoint. Morpholino antisense knockdown in primary chondrocytes, PCNA immunostaining, phospho-Histone H3 staining, BrdU incorporation, flow cytometry Bone Medium 19071237

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2004 Menin associates with a trithorax family histone methyltransferase complex and with the hoxc8 locus. Molecular cell 525 14992727
2010 Ratio of miR-196s to HOXC8 messenger RNA correlates with breast cancer cell migration and metastasis. Cancer research 129 20736365
1993 A mouse homologue of the Drosophila tumour-suppressor gene l(2)gl controlled by Hox-C8 in vivo. Nature 103 8103190
2011 MicroRNA miR-196a controls melanoma-associated genes by regulating HOX-C8 expression. International journal of cancer 101 21077158
2002 Overexpression of the homeobox gene HOXC8 in human prostate cancer correlates with loss of tumor differentiation. The Prostate 98 11813208
2000 Smad1 domains interacting with Hoxc-8 induce osteoblast differentiation. The Journal of biological chemistry 86 10625647
1998 Modification of expression and cis-regulation of Hoxc8 in the evolution of diverged axial morphology. Proceedings of the National Academy of Sciences of the United States of America 84 9482889
1998 Evidence for regulation of cartilage differentiation by the homeobox gene Hoxc-8. Proceedings of the National Academy of Sciences of the United States of America 82 9707582
2005 The identification of Hoxc8 target genes. Proceedings of the National Academy of Sciences of the United States of America 79 15699330
1995 Regulation of Hoxc-8 during mouse embryonic development: identification and characterization of critical elements involved in early neural tube expression. Development (Cambridge, England) 78 8575334
2018 HOXC8 promotes proliferation and migration through transcriptional up-regulation of TGFβ1 in non-small cell lung cancer. Oncogenesis 68 29367650
1999 HOXC5 and HOXC8 expression are selectively turned on in human cervical cancer cells compared to normal keratinocytes. Biochemical and biophysical research communications 67 10208853
2005 Retinaldehyde dehydrogenase 2 and Hoxc8 are required in the murine brachial spinal cord for the specification of Lim1+ motoneurons and the correct distribution of Islet1+ motoneurons. Development (Cambridge, England) 64 15753214
2015 Repression of Hox genes by LMP1 in nasopharyngeal carcinoma and modulation of glycolytic pathway genes by HoxC8. Oncogene 58 25745994
1996 A long-range regulatory element of Hoxc8 identified by using the pClasper vector. Proceedings of the National Academy of Sciences of the United States of America 51 8637890
1996 Combinations of closely situated cis-acting elements determine tissue-specific patterns and anterior extent of early Hoxc8 expression. Proceedings of the National Academy of Sciences of the United States of America 51 8901587
1998 Comparative studies on mammalian Hoxc8 early enhancer sequence reveal a baleen whale-specific deletion of a cis-acting element. Proceedings of the National Academy of Sciences of the United States of America 47 9860988
2017 HOXC8 regulates self-renewal, differentiation and transformation of breast cancer stem cells. Molecular cancer 46 28202042
2006 PLZF regulates Pbx1 transcription and Pbx1-HoxC8 complex leads to androgen-independent prostate cancer proliferation. The Prostate 46 16637071
2010 HOXC8 inhibits androgen receptor signaling in human prostate cancer cells by inhibiting SRC-3 recruitment to direct androgen target genes. Molecular cancer research : MCR 44 21047772
2019 Upregulation of MGP by HOXC8 promotes the proliferation, migration, and EMT processes of triple-negative breast cancer. Molecular carcinogenesis 43 31264274
2020 Downregulation of circNRIP1 Suppresses the Paclitaxel Resistance of Ovarian Cancer via Regulating the miR-211-5p/HOXC8 Axis. Cancer management and research 42 33061608
2012 The crest phenotype in chicken is associated with ectopic expression of HOXC8 in cranial skin. PloS one 41 22514613
2006 Identification of a Hoxc8-regulated transcriptional network in mouse embryo fibroblast cells. Proceedings of the National Academy of Sciences of the United States of America 41 16793922
2021 FMR1/circCHAF1A/miR-211-5p/HOXC8 feedback loop regulates proliferation and tumorigenesis via MDM2-dependent p53 signaling in GSCs. Oncogene 40 34017077
1998 Multiple phases of expression and regulation of mouse Hoxc8 during early embryogenesis. The Journal of experimental zoology 37 9723177
2020 DLX5 and HOXC8 enhance the chondrogenic differentiation potential of stem cells from apical papilla via LINC01013. Stem cell research & therapy 36 32631410
2011 HOXC8-Dependent Cadherin 11 Expression Facilitates Breast Cancer Cell Migration through Trio and Rac. Genes & cancer 36 22593800
2010 Lsh mediated RNA polymerase II stalling at HoxC6 and HoxC8 involves DNA methylation. PloS one 36 20161795
2014 HOXC8 promotes breast tumorigenesis by transcriptionally facilitating cadherin-11 expression. Oncotarget 33 24810778
2022 Control of spinal motor neuron terminal differentiation through sustained Hoxc8 gene activity. eLife 31 35315772
2014 The survival predictive significance of HOXC6 and HOXC8 in esophageal squamous cell carcinoma. The Journal of surgical research 31 24525058
2008 Transcription factor Ap2delta associates with Ash2l and ALR, a trithorax family histone methyltransferase, to activate Hoxc8 transcription. Proceedings of the National Academy of Sciences of the United States of America 31 18495928
2011 Expression of HOXC8 is inversely related to the progression and metastasis of pancreatic ductal adenocarcinoma. British journal of cancer 28 21712827
1999 Hematopoietic progenitor cell abnormalities in Hoxc-8 null mutant mice. The Journal of experimental zoology 27 9919689
2010 Expression of cartilage developmental genes in Hoxc8- and Hoxd4-transgenic mice. PloS one 26 20126390
2017 Interleukin enhancer-binding factor 3 and HOXC8 co-activate cadherin 11 transcription to promote breast cancer cells proliferation and migration. Oncotarget 25 29296180
2024 N6-methyladenosine-modified circSLCO1B3 promotes intrahepatic cholangiocarcinoma progression via regulating HOXC8 and PD-L1. Journal of experimental & clinical cancer research : CR 24 38641828
2003 Divergence of Hoxc8 early enhancer parallels diverged axial morphologies between mammals and fishes. Proceedings of the National Academy of Sciences of the United States of America 24 14673077
2015 Hoxc8 initiates an ectopic mammary program by regulating Fgf10 and Tbx3 expression and Wnt/β-catenin signaling. Development (Cambridge, England) 21 26459221
2010 Mouse Homologue of the Schizophrenia Susceptibility Gene ZNF804A as a Target of Hoxc8. Journal of biomedicine & biotechnology 19 20508826
2020 LncRNA SNHG1 Regulates the Progression of Esophageal Squamous Cell Cancer by the miR-204/HOXC8 Axis. OncoTargets and therapy 18 32158227
2017 Molecular characterization of HOXC8 gene and methylation status analysis of its exon 1 associated with the length of cashmere fiber in Liaoning cashmere goat. Genetica 17 28093668
2003 Normal proliferation and differentiation of Hoxc-8 transgenic chondrocytes in vitro. BMC developmental biology 17 12713673
2020 MiR-148a-3p may contribute to flawed decidualization in recurrent implantation failure by modulating HOXC8. Journal of assisted reproduction and genetics 16 32772270
2016 Effect of rs11614913 Polymorphism on Mature miR196a2 Expression and its Target Gene HOXC8 Expression in Human Glioma. Journal of molecular neuroscience : MN 16 27796868
2020 An Integrated Genomic Approach Identifies HOXC8 as an Upstream Regulator in Ovarian Endometrioma. The Journal of clinical endocrinology and metabolism 15 32877504
2015 Embigin, regulated by HOXC8, plays a suppressive role in breast tumorigenesis. Oncotarget 15 26090721
2006 Multiple roles of hoxc8 in skeletal development. Annals of the New York Academy of Sciences 15 16831908
2009 Hoxc8 represses BMP-induced expression of Smad6. Molecules and cells 14 20016939
2008 Morpholino-mediated knockdown in primary chondrocytes implicates Hoxc8 in regulation of cell cycle progression. Bone 13 19071237
2010 Proliferating cell nuclear antigen (Pcna) as a direct downstream target gene of Hoxc8. Biochemical and biophysical research communications 12 20097160
2007 Effect of excessive iodine exposure on the placental deiodinase activities and Hoxc8 expression during mouse embryogenesis. The British journal of nutrition 12 17456249
2005 Dynamic expression pattern of Hoxc8 during mouse early embryogenesis. The anatomical record. Part A, Discoveries in molecular, cellular, and evolutionary biology 12 15674821
2003 Analysis of plausible downstream target genes of Hoxc8 in F9 teratocarcinoma cells. Putative downstream target genes of Hoxc8. Molecular biology reports 12 12974468
2022 Association of HOXC8 Genetic Polymorphisms with Multi-Vertebral Number and Carcass Weight in Dezhou Donkey. Genes 11 36421849
2006 Expression of folate pathway genes in the cartilage of Hoxd4 and Hoxc8 transgenic mice. Birth defects research. Part A, Clinical and molecular teratology 11 16586448
2009 In vitro osteoblast differentiation is negatively regulated by Hoxc8. Applied biochemistry and biotechnology 10 19214787
2004 Comparative cis-regulatory analyses identify new elements of the mouse Hoxc8 early enhancer. Journal of experimental zoology. Part B, Molecular and developmental evolution 10 15384168
2023 HOXC8/TGF-β1 positive feedback loop promotes liver fibrosis and hepatic stellate cell activation via activating Smad2/Smad3 signaling. Biochemical and biophysical research communications 9 37099809
2012 Cdx1 is essential for the initiation of HoxC8 expression during early embryogenesis. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 9 22426122
2004 Hoxc8 early enhancer of the Indonesian coelacanth, Latimeria menadoensis. Journal of experimental zoology. Part B, Molecular and developmental evolution 9 15470754
2025 CAF-derived exosomal miR-196b-5p after androgen deprivation therapy promotes epithelial-mesenchymal transition in prostate cancer cells through HOXC8/NF-κB signaling pathway. Biology direct 8 40615904
2007 Comparison of diverged Hoxc8 early enhancer activities reveals modification of regulatory interactions at conserved cis-acting elements. Journal of experimental zoology. Part B, Molecular and developmental evolution 8 17171696
2023 Comprehensive analysis of HOXC8 associated with tumor microenvironment characteristics in colorectal cancer. Heliyon 7 37885723
2022 Histone demethylase KDM5A regulates the functions of human periodontal ligament stem cells during periodontitis via the miR-495-3p/HOXC8 axis. Regenerative therapy 7 35509266
2016 Genes Frequently Coexpressed with Hoxc8 Provide Insight into the Discovery of Target Genes. Molecules and cells 7 27025388
2008 The third helix of the murine Hoxc8 homeodomain facilitates protein transduction in mammalian cells. Biochemical and biophysical research communications 7 18835255
2008 The third helix of the Hoxc8 homeodomain peptide enhances the efficiency of gene transfer in combination with lipofectamine. Molecular biotechnology 7 18991027
2007 Mouse naked cuticle 2 (mNkd2) as a direct transcriptional target of Hoxc8 in vivo. Journal of experimental zoology. Part A, Ecological genetics and physiology 7 17094106
2002 Hoxc-8 expression shows left-right asymmetry in the posterior lateral plate mesoderm. Gene expression patterns : GEP 7 12617829
2017 Gdf11/Smad signalling and Cdx proteins cooperate to activate the Hoxc8 early enhancer in HepG2 cells. The International journal of developmental biology 6 28695962
2024 DNA Methylation-Regulated HOXC8's Role in HER2-Positive Breast Cancer Function and its Contribution to Herceptin Resistance. Discovery medicine 5 38531796
2023 HOXC8 mediates osteopontin expression in gastric cancer cells. Journal of Cancer 5 37670969
2021 miR-301a inhibits adipogenic differentiation of adipose-derived stromal vascular fractions by targeting HOXC8 in sheep. Animal science journal = Nihon chikusan Gakkaiho 5 34856652
2019 miR-152 inhibits the proliferation and invasion of chordoma cells by targeting HOXC8. The Journal of international medical research 5 31638463
2016 The predictive potential and oncogenic effects of HOXC8 expression on osteosarcoma. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 5 27651160
2009 Generation of conditional Hoxc8 loss-of-function and Hoxc8-->Hoxc9 replacement alleles in mice. Genesis (New York, N.Y. : 2000) 5 19621436
2005 Homology modeling based solution structure of Hoxc8-DNA complex: role of context bases outside TAAT stretch. Journal of biomolecular structure & dynamics 5 15842175
2003 Phylogenetic analysis of the mammalian Hoxc8 non-coding region. Journal of structural and functional genomics 5 12836698
1991 Molecular cloning, chromosomal assignment, and nucleotide sequence of the feline homeobox HOX3A. Genomics 5 1686012
2025 HOXC8 impacts lung tumorigenesis by preventing pyroptotic cell death through the suppression of caspase-1 expression. Cell death & disease 4 40701951
2025 Methionine restriction alleviates kidney fibrosis through epigenetic repression of the TGF-β-Smad3-Hoxc8/P-TEFb axis. Nature communications 4 41476080
2018 Evaluation of HOXC8 in crested Swiss chicken. Animal genetics 4 29774580
2006 Efficient cellular uptake of recombinant murine Hoxc8 homeoprotein in COS-7 cells. Life sciences 4 16949104
2023 Chicken HOXC8 and HOXC10 genes may play a role in the altered skull morphology associated with the Crest phenotype. Journal of experimental zoology. Part B, Molecular and developmental evolution 3 37039065
2022 HOXC8 alleviates high glucose-triggered damage of trophoblast cells during gestational diabetes mellitus via activating TGFβ1-mediated Notch1 pathway. Human cell 3 36308681
2018 HOXC8: a predictive glioma biomarker that induces epithelia-mesenchymal transition. Chinese neurosurgical journal 3 32922885
2024 Human papillomavirus type 16 E7 promotes cell viability and migration in cervical cancer by regulating the miR-23a/HOXC8 axis. Journal of obstetrics and gynaecology : the journal of the Institute of Obstetrics and Gynaecology 2 38348790
2024 Effect of whole-process high-quality nursing on the quality of life of acute pancreatitis patients and the mechanism of miR-126-5p/HOXC8 axis promoting the progression of acute pancreatitis. Cellular and molecular biology (Noisy-le-Grand, France) 2 39262244
2024 lncRNA WAC-AS1 promotes the progression of gastric cancer through miR-204-5p/HOXC8 axis. Translational oncology 2 39395273
2023 Effects of HOXC8 on the Proliferation and Differentiation of Porcine Preadipocytes. Animals : an open access journal from MDPI 2 37627406
2003 Xenopus hoxc8 during early development. Biochemical and biophysical research communications 2 12480513
2025 HOXC8-activated TRIM22/NF-κB pathway promotes stemness in colorectal cancer. Cancer letters 1 41265630
2024 Identification of a Chondrocyte-Specific Enhancer in the Hoxc8 Gene. Journal of developmental biology 1 38390956
2019 Retracted Article: Long noncoding RNA DLEU1 promotes cell proliferation and migration of Wilms tumor through the miR-300/HOXC8 axis. RSC advances 1 35542655
2008 Membrane transducing activity of recombinant Hoxc8 protein and its possible application as a gene delivery vector. Experimental & molecular medicine 1 18446053
2026 Establishment of a xenograft model of endometriosis-associated fibrosis using human immortalized endometrial stromal cells overexpressing HOXC8. Scientific reports 0 41760717
2025 HOXC8 derived from cancer-associated fibroblasts regulates lung cancer cell malignant metastasis and ferroptosis by mediating the transcription of GCH1. Pathology, research and practice 0 41505981
2021 Retraction: Long noncoding RNA DLEU1 promotes cell proliferation and migration of Wilms tumor through the miR-300/HOXC8 axis. RSC advances 0 35427068

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