Affinage

HOXB7

Homeobox protein Hox-B7 · UniProt P09629

Length
217 aa
Mass
24.0 kDa
Annotated
2026-04-28
100 papers in source corpus 29 papers cited in narrative 29 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

HOXB7 is a homeodomain transcription factor that drives cell proliferation, epithelial-mesenchymal transition, angiogenesis, DNA repair, and stem/progenitor cell expansion across multiple tissue contexts. It directly transactivates target gene promoters including bFGF, EGFR, TGFβ2, and LIN28B, acting through TALE cofactors PBX2/PREP1 and the coactivator CBP, while its transcriptional output is negatively regulated by PARP-1-mediated poly(ADP-ribosyl)ation of its C-terminal glutamate-rich tail (PMID:8756643, PMID:17018609, PMID:25542862, PMID:29576613, PMID:10435624, PMID:18378073, PMID:22844406). Beyond transcriptional regulation, HOXB7 physically interacts with the Ku70/Ku80/DNA-PKcs complex to enhance non-homologous end joining, conferring resistance to DNA-damaging agents (PMID:17308091, PMID:31568655). HOXB7 cooperates with ERα as a transcriptional co-activator at ER target genes including HER2, establishing a MYC–HOXB7–HER2 positive feedback loop that drives tamoxifen resistance in breast cancer, while its own expression is epigenetically silenced by EZH2/PRC2-mediated H3K27 trimethylation and post-transcriptionally repressed by miR-196a (PMID:26180042, PMID:21690342, PMID:24853421, PMID:20480203).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 1996 High

    Establishing that HOXB7 is a direct transcriptional activator of the bFGF gene resolved how a homeodomain protein could drive melanoma cell proliferation through a specific growth factor target.

    Evidence Band shift assay demonstrating direct DNA binding to bFGF promoter, cotransfection reporter assay, and antisense oligomer knockdown abolishing bFGF expression in melanoma cells

    PMID:8756643

    Open questions at the time
    • Identity of additional direct HOXB7 target genes beyond bFGF was unknown
    • Whether bFGF is the sole mediator of HOXB7-driven proliferation was untested
    • Genome-wide binding profile not yet determined
  2. 1998 High

    Knockout studies in mice established that Hoxb7 has a developmental role in axial skeletal patterning, with functional redundancy with its paralog Hoxa7, grounding HOXB7 in classical Hox gene biology.

    Evidence Hoxb7-/- mice showing rib defects at 12% penetrance; Hoxa7/Hoxb7 double knockouts with increased penetrance and expressivity

    PMID:9784603

    Open questions at the time
    • Low penetrance of single knockout leaves open whether additional paralogs compensate
    • No hematopoietic or oncogenic phenotype assessed in knockout mice
  3. 1999 High

    Discovery that CBP and IκB-α serve as HOXB7 cofactors established how HOXB7 transactivation is amplified, revealing that its activity depends on chromatin-modifying and signaling-associated coactivators.

    Evidence Co-immunoprecipitation and GST pull-down for CBP and IκB-α interactions; domain mapping; reporter assays showing enhanced transcriptional activity

    PMID:10026139 PMID:10435624

    Open questions at the time
    • Whether CBP and IκB-α cooperate on the same promoters was not tested
    • Endogenous target gene regulation by these cofactors was not shown
    • IκB-α co-activation mechanism (non-NF-κB) remained unexplained
  4. 1999 Medium

    Demonstrating that HOXB7 expands primitive hematopoietic progenitors and promotes myeloid-biased self-renewal placed HOXB7 as a regulator of stem/progenitor cell fate decisions beyond solid tissues.

    Evidence Retroviral transduction of purified human HPCs with HPP-CFC and LTC-IC assays showing expanded myeloid progenitors

    PMID:10208421

    Open questions at the time
    • Direct transcriptional targets mediating progenitor expansion were unknown
    • In vivo repopulation assays were not performed
    • Mechanism distinguishing self-renewal from differentiation block was unclear
  5. 2001 Medium

    Structure-function mutagenesis revealed that HOXB7's Pbx-binding pentapeptide and homeodomain are essential for blocking myeloid differentiation, while the C-terminal glutamate-rich region restrains its activity, defining functional domain architecture.

    Evidence Site-directed mutagenesis of HOXB7 domains in 32D myeloid cells with G-CSF differentiation assay

    PMID:11290787

    Open questions at the time
    • Biochemical basis for C-terminal auto-inhibition was not resolved
    • Endogenous target genes mediating differentiation block were not identified
  6. 2001 Medium

    Showing that HOXB7 orchestrates a pro-angiogenic transcriptional program (VEGF, IL-8, angiopoietin-2) while suppressing angiopoietin-1 extended its role from single-target transactivation to coordinated regulation of tumor vascularization.

    Evidence Retroviral HOXB7 overexpression in breast cancer cells with gene expression profiling, in vitro angiogenesis coculture, and vascularized xenografts

    PMID:11522651

    Open questions at the time
    • Direct vs. indirect transcriptional control of angiogenic targets was not distinguished
    • Whether bFGF mediates all angiogenic effects was untested
  7. 2006 High

    Establishing that HOXB7 induces EMT through bFGF-dependent Ras-MAPK activation resolved the signaling cascade linking a homeodomain transcription factor to mesenchymal transformation and invasion.

    Evidence HOXB7 overexpression in MCF10A/MDCK cells with pharmacologic FGF receptor and Ras-MAPK inhibitors reversing EMT; siRNA rescue; xenograft validation

    PMID:17018609

    Open questions at the time
    • Whether HOXB7 activates EMT transcription factors (Snail, Twist) directly was unknown
    • Contribution of non-bFGF targets to EMT was not tested
  8. 2007 High

    Discovery that HOXB7 physically associates with the Ku70/Ku80/DNA-PKcs complex and enhances NHEJ revealed an unexpected non-transcriptional function in DNA double-strand break repair.

    Evidence GST pull-down and reciprocal co-immunoprecipitation identifying Ku70, Ku80, DNA-PKcs as partners; NHEJ repair assay in vitro and in vivo; siRNA knockdown

    PMID:17308091

    Open questions at the time
    • Whether HOXB7 stimulates DNA-PKcs kinase activity or merely scaffolds the complex was unclear
    • Relative contribution of transcriptional vs. non-transcriptional mechanisms to radiation resistance was not separated
  9. 2008 Medium

    Showing that TALE cofactors PBX2/PREP1 are required for HOXB7 oncogenic activity established that HOXB7 does not act as a monomer in cancer but depends on heterodimeric cofactor complexes.

    Evidence Dominant-negative Pbx1 mutant sequestering Prep1 in cytoplasm and ablating HOXB7-driven tumorigenesis in vitro and in vivo

    PMID:18378073

    Open questions at the time
    • Genome-wide identification of PBX2/HOXB7-co-occupied sites was not performed
    • Whether PBX2 selectivity over PBX1 reflects differential expression or binding affinity was unknown
  10. 2012 High

    Identifying PARP-1-mediated poly(ADP-ribosyl)ation of the HOXB7 C-terminal glutamate-rich tail as a negative regulatory mechanism explained the earlier observation that this tail restrains HOXB7 transcriptional activity.

    Evidence Co-IP, GST pull-down, in vitro ADP-ribosylation assay, deletion mutagenesis removing Glu-rich tail, luciferase reporter

    PMID:22844406

    Open questions at the time
    • Whether PARP-1 regulation of HOXB7 occurs in physiological contexts (not just overexpression) was untested
    • Specific ADP-ribosylation sites on HOXB7 were not mapped at residue level
  11. 2011 High

    Demonstrating that HOXB7 directly binds the EGFR promoter to drive tamoxifen resistance revealed a second major direct transcriptional target and linked HOXB7 to endocrine therapy failure.

    Evidence ChIP and luciferase reporter assay in MCF-7 cells; long-term tamoxifen treatment model; siRNA knockdown restoring sensitivity

    PMID:21690342

    Open questions at the time
    • Whether HOXB7 binds EGFR promoter as monomer or with PBX cofactors was not determined
    • Patient stratification by HOXB7 levels for tamoxifen response was not clinically validated
  12. 2014 High

    Identifying TGFβ2 as a direct HOXB7 target driving metastasis and M2 macrophage recruitment expanded HOXB7's role to tumor microenvironment remodeling beyond cell-autonomous effects.

    Evidence ChIP and luciferase validation at TGFβ2 promoter; TGFβ2 siRNA/inhibitor rescue; MMTV transgenic and xenograft lung metastasis models

    PMID:25542862

    Open questions at the time
    • Whether HOXB7 directly transcribes macrophage chemoattractants beyond TGFβ2 was unknown
    • Contribution of TGFβ2-independent HOXB7 targets to metastasis was not quantified
  13. 2014 Medium

    Revealing that EZH2/PRC2-mediated H3K27me3 silences the HOXB7 locus (recruited by TUG1 lncRNA) established an epigenetic layer controlling HOXB7 expression upstream of its transcriptional and post-transcriptional regulators.

    Evidence ChIP assay showing EZH2 occupancy and H3K27me3 at HOXB7 promoter; TUG1 knockdown derepressing HOXB7; downstream AKT/MAPK activation in NSCLC

    PMID:24853421

    Open questions at the time
    • Direct RNA-protein interaction between TUG1 and PRC2 at the HOXB7 locus was not demonstrated by RIP or CHART
    • Whether PRC2 regulation of HOXB7 is tissue-specific was not tested
  14. 2015 Medium

    Mapping 1,504 genome-wide HOXB7 binding sites by ChIP-seq provided the first unbiased view of HOXB7's chromatin occupancy, validating known targets and identifying new ones including CTNND2 and SCGB1D2.

    Evidence ChIP-seq in BT-474 cells with ChIP-qPCR validation across multiple breast cancer cell lines

    PMID:26014856

    Open questions at the time
    • Functional validation of most binding sites was not performed
    • Cofactor co-occupancy (PBX2, ERα) at these sites was not assessed
  15. 2015 High

    Elucidation of the MYC–miR-196a–HOXB7–ERα–HER2 positive feedback loop explained how HOXB7 sustains tamoxifen resistance through physical interaction with ERα and co-activation of HER2 transcription.

    Evidence Reciprocal ChIP and co-IP for HOXB7-ERα; MYC inhibitor disrupting the loop; xenograft regression

    PMID:26180042

    Open questions at the time
    • Structural basis of HOXB7-ERα interaction was not determined
    • Whether this feedback loop operates in other ER+ cancers beyond breast was untested
  16. 2018 Medium

    Identification of LIN28B as a direct HOXB7 transcriptional target linked HOXB7 to cancer stemness and cellular reprogramming, explaining its capacity to expand stem cell populations.

    Evidence HOXB7 overexpression driving LIN28B upregulation and iPSC reprogramming at efficiency comparable to LIN28B or c-MYC

    PMID:29576613

    Open questions at the time
    • ChIP evidence for direct HOXB7 binding at LIN28B promoter was implied but not explicitly shown with full controls
    • Whether let-7 miRNA repression downstream of LIN28B mediates HOXB7's stemness effects was not tested
  17. 2019 Medium

    Replication of HOXB7–Ku70/Ku80/DNA-PKcs interaction in esophageal cancer cells and demonstration that disrupting HOXB7/PBX dimers sensitizes tumors to cisplatin reinforced the DNA repair function and established therapeutic relevance of targeting HOXB7 cofactor interactions.

    Evidence GST pull-down and co-IP confirming prior interaction findings; HXR9 peptide synergizing with cisplatin in vitro and in vivo

    PMID:31568655

    Open questions at the time
    • Whether HOXB7 enhances repair of cisplatin-induced interstrand crosslinks specifically via NHEJ or other pathways was unclear
    • HXR9 peptide targets multiple HOX-PBX dimers, not HOXB7-specific

Open questions

Synthesis pass · forward-looking unresolved questions
  • The structural basis of HOXB7 interactions with ERα, DNA-PKcs, and PBX2, and the genome-wide identification of cofactor-dependent versus cofactor-independent HOXB7 target genes, remain unresolved.
  • No crystal or cryo-EM structure of HOXB7 in complex with any partner
  • Genome-wide cofactor co-occupancy studies (e.g., PBX2/ERα ChIP-seq) have not been performed alongside HOXB7 ChIP-seq
  • Relative contributions of transcriptional vs. non-transcriptional (NHEJ) functions to in vivo phenotypes are not separated

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 7 GO:0003677 DNA binding 4
Localization
GO:0005634 nucleus 4 GO:0005886 plasma membrane 1
Pathway
R-HSA-74160 Gene expression (Transcription) 6 R-HSA-162582 Signal Transduction 4 R-HSA-73894 DNA Repair 2 R-HSA-1266738 Developmental Biology 1
Partners
CBPESR1PARP1PBX2PREP1PRKDCXRCC5XRCC6
Complex memberships
HOXB7-ERαHOXB7-PBX2-PREP1Ku70/Ku80/DNA-PKcs

Evidence

Reading pass · 29 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1996 HOXB7 directly transactivates the basic fibroblast growth factor (bFGF) gene through one of five putative homeodomain binding sites in its promoter, driving melanoma cell proliferation; antisense oligomers targeting HOXB7 mRNA abolished bFGF expression and inhibited cell proliferation. Band shift assay, cotransfection/reporter assay, antisense oligomer knockdown Molecular and cellular biology High 8756643
2001 HOXB7 upregulates multiple pro-angiogenic factors (VEGF, GROα/MGSA, IL-8, angiopoietin-2) and MMP-9 while abrogating angiopoietin-1, driving a tumor-associated angiogenic switch in breast cancer cells and promoting vascularized tumor formation in vivo. Gene expression profiling, retroviral transduction, in vitro coculture angiogenesis assay, xenograft in nude mice with CD31/CD34 immunostaining Cancer research Medium 11522651
2006 Overexpression of HOXB7 in epithelial cells induces epithelial-mesenchymal transition (EMT), upregulates bFGF, activates Ras and RhoA GTPases, increases phospho-ERK1/2 (MAPK), and promotes migration, invasion, and vascularized tumor formation; effects reversed by FGF receptor and Ras-MAPK inhibitors and by HOXB7-specific siRNA. Stable transfection/overexpression in MCF10A and MDCK cells, siRNA knockdown, Ras/RhoA activity assays, Western blot, xenograft in mice, pharmacologic inhibition Cancer research High 17018609
2007 HOXB7 physically interacts with the DNA-dependent protein kinase holoenzyme components Ku70, Ku80, and DNA-PKcs, and with PARP, identified by GST pull-down/affinity chromatography and confirmed by co-immunoprecipitation; HOXB7 expression enhances non-homologous end joining (NHEJ) DNA double-strand break repair in vitro and in vivo, conferring radiation resistance. GST pull-down, co-immunoprecipitation, NHEJ repair assay in vitro and in vivo, siRNA knockdown Cancer research High 17308091
1999 HOXB7 physically interacts with the coactivator CBP (CREB-binding protein) both in vitro and in vivo; this interaction requires the HOXB7 N-terminal domain and two C-terminal CBP domains, and enhances HOXB7 transactivation potential; histone deacetylase inhibition (trichostatin A) further augments HOXB7 transcriptional activity. Co-immunoprecipitation in vivo, GST pull-down in vitro, deletion/domain mapping, transient transfection reporter assay Oncogene High 10435624
1999 IκB-α physically interacts with HOXB7 via its ankyrin repeats and C-terminal domain (binding HOXB7 N-terminal domain) and markedly increases HOXB7-dependent transcription from a homeodomain consensus reporter, revealing IκB-α as a positive co-regulator of homeodomain protein transcriptional activity. In vitro binding assay, co-immunoprecipitation, transient transfection reporter assay The Journal of biological chemistry Medium 10026139
2001 Mutations in the Pbx-binding pentapeptide motif or the DNA-binding homeodomain abolish HOXB7's ability to inhibit G-CSF-induced myeloid differentiation; mutations at casein kinase II phosphorylation sites or deletion of the C-terminal glutamate-rich region or N-terminal 14 aa actually enhance differentiation, defining functional regions of HOXB7. Site-directed mutagenesis, stable retroviral transduction of 32D myeloid cells, G-CSF differentiation assay Journal of immunology Medium 11290787
2011 HOXB7 directly binds the EGFR promoter to enhance its transcription (demonstrated by ChIP and luciferase assay), rendering MCF-7 cells resistant to tamoxifen through cross-talk between EGFR signaling and ERα; HOXB7 is itself an ERα-responsive gene and its expression progressively increases with long-term tamoxifen treatment. ChIP, luciferase reporter assay, long-term tamoxifen treatment model, siRNA knockdown Proceedings of the National Academy of Sciences of the United States of America High 21690342
2014 HOXB7 directly binds and activates the TGFβ2 promoter (shown by luciferase and ChIP assays), upregulating TGFβ/SMAD3 signaling to promote breast cancer cell migration, invasion, and lung metastasis; HOXB7 also induces M2 tumor-associated macrophage recruitment via TGFβ2. Luciferase reporter assay, ChIP, TGFβ2 siRNA/pharmacologic inhibition, xenograft lung metastasis model, MMTV transgenic mice Cancer research High 25542862
2015 HOXB7 physically interacts with ERα (demonstrated by ChIP and co-immunoprecipitation); the HOXB7-ERα complex enhances transcription of multiple ERα target genes including HER2; MYC (stabilized by EGFR-HER2 signaling phosphorylation) inhibits miR-196a transcription, relieving repression of HOXB7 to form a MYC-HOXB7-HER2 positive feedback loop in tamoxifen-resistant breast cancer. ChIP, co-immunoprecipitation, luciferase reporter assay, MYC small-molecule inhibitors, xenograft regression Cancer discovery High 26180042
2012 PARP-1 physically interacts with HOXB7 via the HOXB7 homeodomain and PARP-1 first zinc finger domain; PARP-1 poly(ADP-ribosyl)ates HOXB7, primarily on the C-terminal glutamate-rich tail, reducing HOXB7 transcriptional activity; deletion of the Glu-rich tail abolishes ADP-ribosylation and renders HOXB7 more transcriptionally active. Co-immunoprecipitation, GST pull-down, ADP-ribosylation assay, deletion mutagenesis, luciferase reporter assay PloS one High 22844406
2003 The HOXB7 promoter is regulated by direct binding of NF-Y, YY1, Sp1/Sp3, and USF-1 transcription factors; site-specific mutagenesis of their binding sites reduced HOXB7 promoter activity by 55–78%. Electrophoretic mobility shift assay (EMSA), cell transfection, site-directed mutagenesis, reporter assay Biochimica et biophysica acta Medium 12697323
2013 HOXB7 forms a dimer with PBX2 that acts as a positive transcriptional regulator of oncogenic miR-221 and miR-222; disruption of HOXB7/PBX2 dimers (by HXR9 peptide) reduces miR-221/222 transcription and elevates c-FOS expression, leading to melanoma cell death. HXR9 peptide (HOX/PBX dimerization antagonist), luciferase reporter, ChIP, cell death assays in melanoma cell lines International journal of cancer Medium 23400877
2008 Oncogenic HOXB7 activity in breast cancer cells requires TALE cofactors; HOXB7 increases expression of Pbx2 and Prep1 while decreasing Pbx1; a dominant-negative Pbx1 mutant (Pbx1NT) sequesters Prep1 in the cytoplasm, reducing tumorigenic properties of HOXB7-transduced cells and increasing apoptosis, p16, and p53. Retroviral transduction, dominant-negative mutant, in vitro and in vivo tumor assays, Western blot Cancer letters Medium 18378073
1999 Enforced HOXB7 expression in human hematopoietic stem/progenitor cells (HSCs/HPCs) promotes self-renewal and proliferation of primitive HPCs and putative HSCs, and specifically expands granulo-monocytic progenitors with sustained proliferation, suggesting a role in myeloid-biased progenitor expansion. Retroviral transduction of purified human peripheral blood HPCs, HPP-CFC assay, LTC-IC assay, clonogenic assay, liquid suspension culture Oncogene Medium 10208421
1998 Hoxb7 expression in mammary epithelial cells is regulated by the extracellular matrix (ECM): culturing on a basement membrane induces Hoxb7 downregulation, indicating ECM-dependent transcriptional control of HOXB7 in the mammary gland. RT-PCR, cell culture on basement membrane vs. inert substratum (polyHEMA), comparison of mouse mammary epithelial cell lines Journal of cellular biochemistry Low 9620166
2010 miR-196a directly represses HOXB7 mRNA and protein levels; reduced miR-196a in melanoma cells leads to elevated HOXB7, which induces Ets-1 activity via bFGF upregulation, ultimately driving BMP4 overexpression and enhanced melanoma cell migration. miR-196a mimic/inhibitor transfection, Western blot, reporter assay (implied), functional migration assay Cellular and molecular life sciences Medium 20480203
2015 During mesenchymal stromal cell (MSC) aging, miR-196a upregulation inversely correlates with HOXB7 expression; forced HOXB7 expression reduces senescence, improves proliferation and osteogenesis, and dramatically increases autocrine bFGF secretion, placing HOXB7 as a master regulator downstream of miR-196a in MSC aging. miR-196a overexpression, lentiviral HOXB7 overexpression, proliferation/senescence/osteogenesis assays, bFGF ELISA, in vivo skeletal aging model in mice Stem cells Medium 25428821
2017 HOXB7 localizes to cell membrane protrusions in migrating pancreatic cancer cells; HOXB7 knockdown reduces protrusions and decreases ERK1/2 phosphorylation without altering active Rho GTPase levels; HOXB7-driven ERK1/2 activation selectively stimulates JNK and HSP27 phosphorylation to promote cell motility and invasiveness. Immunocytochemistry (subcellular localization), siRNA knockdown, rescue construct, Western blot for phospho-ERK1/2/JNK/HSP27, motility and invasion assays The Journal of biological chemistry Medium 28912272
2019 HOXB7 interacts with Ku70, Ku80, and DNA-PKcs (confirmed by GST pull-down and co-immunoprecipitation) in esophageal squamous cell carcinoma cells; HOXB7 knockdown reduces expression of these DNA repair proteins, sensitizes cells to cisplatin, and causes S-phase arrest; the HXR9 peptide (HOXB7/PBX dimerization antagonist) synergistically enhances cisplatin sensitivity. GST pull-down, co-immunoprecipitation, immunofluorescent colocalization, siRNA knockdown, CCK8 assay, flow cytometry, in vivo tumor model Thoracic cancer Medium 31568655
2015 Genome-wide ChIP-seq identified 1,504 HOXB7 chromatin binding sites in BT-474 breast cancer cells; 17 sites validated by ChIP-qPCR across multiple cell lines; direct HOXB7 target genes identified near binding sites include CTNND2 and SCGB1D2. ChIP-seq, ChIP-qPCR validation, gene expression analysis International journal of cancer Medium 26014856
2018 HOXB7 upregulates LIN28B (a pluripotency factor and cancer gene) as a direct transcriptional target, sustaining cancer stem cell expansion; HOXB7 overexpression enhances reprogramming to iPSCs with efficiency comparable to LIN28B or c-MYC. ChIP (implied for direct target), gene expression profiling, iPSC reprogramming assay, stem cell marker analysis, siRNA knockdown Oncogene Medium 29576613
2000 Overexpression of HOXB7 in multipotent C3H10T1/2 cells increases proliferation 3.5-fold and induces smooth muscle cell (SMC) differentiation (upregulating calponin and SM22α by 3–4-fold) without promoting osteogenic or chondrogenic lineages; HOXB7 expression was detected in human atherosclerotic plaques. Retroviral overexpression, semi-quantitative RT-PCR for SMC markers, cell morphology analysis, proliferation assay Journal of cellular biochemistry Medium 10842316
1998 Cis-acting regulatory elements within 3.5 kb upstream of Hoxb-7 cooperate to establish anterior-posterior restricted expression; deletion analysis identifies at least three control elements including one that confers Hox-like A-P expression boundaries in an orientation- and promoter-dependent manner in transgenic mice. Transgenic mouse reporter (lacZ), deletion analysis, in vivo expression analysis Development (Cambridge, England) Medium 8104144
1998 In mice, Hoxb7 homozygous knockout causes first and second rib defects (12% penetrance); Hoxa7/Hoxb7 double knockouts show higher penetrance and increased expressivity of upper thoracic rib defects, demonstrating functional redundancy between paralogous Hox genes in axial skeletal patterning. Gene targeting/knockout in mice (Hoxa7-/- and Hoxb7-/-), skeletal analysis of double mutants Mechanisms of development High 9784603
2014 TUG1 lncRNA, induced by p53, recruits PRC2 to the HOXB7 promoter; ChIP assays show EZH2 binds the HOXB7 locus and H3K27 trimethylation silences HOXB7 expression; TUG1 knockdown upregulates HOXB7, which in turn activates AKT and MAPK pathways to promote NSCLC proliferation. ChIP assay (EZH2 and H3K27me3 at HOXB7 promoter), luciferase assay (p53 binding to TUG1 promoter), siRNA knockdown, in vitro and in vivo proliferation assays Cell death & disease Medium 24853421
1998 Synergistic activation of the Purkinje cell-specific pcp-2(L7) gene promoter is achieved by co-expression of HoxB7 and HoxA5 acting on the L7ATE element; in contrast, En-2 represses the same promoter, demonstrating combinatorial homeodomain protein control of a neuron-specific gene. Cotransfection reporter assay in vitro, RT-PCR to confirm expression in cerebellar Purkinje cells Journal of neurobiology Medium 9740027
2017 HOXB7 knockdown in gastric cancer cells inhibits invasion and migration while activating HOXB7 overexpression promotes these phenotypes via downregulation of PTEN and activation of phospho-Akt signaling. siRNA knockdown, cDNA overexpression, Matrigel invasion and wound healing assays, Western blot for phospho-Akt and PTEN Journal of gastroenterology and hepatology Low 26968988
2018 HOXB7 knockdown in cutaneous squamous cell carcinoma cells inhibits Wnt/β-catenin pathway activation; co-immunoprecipitation demonstrates that endogenous HOXB7 physically binds β-catenin, linking HOXB7 to Wnt signaling in CSCC. Co-immunoprecipitation, siRNA knockdown, Western blot for Wnt pathway components, xenograft tumor model American journal of physiology. Cell physiology Low 30067384

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1989 Segmental expression of Hox-2 homoeobox-containing genes in the developing mouse hindbrain. Nature 515 2571936
1990 Sequential activation of HOX2 homeobox genes by retinoic acid in human embryonal carcinoma cells. Nature 474 1975088
1992 Exogenous retinoic acid rapidly induces anterior ectopic expression of murine Hox-2 genes in vivo. Development (Cambridge, England) 442 1363087
2014 P53-regulated long non-coding RNA TUG1 affects cell proliferation in human non-small cell lung cancer, partly through epigenetically regulating HOXB7 expression. Cell death & disease 382 24853421
1993 The zinc finger gene Krox20 regulates HoxB2 (Hox2.8) during hindbrain segmentation. Cell 291 8093858
1990 Isolation of the mouse Hox-2.9 gene; analysis of embryonic expression suggests that positional information along the anterior-posterior axis is specified by mesoderm. Development (Cambridge, England) 287 1983472
1991 Introduction of a subtle mutation into the Hox-2.6 locus in embryonic stem cells. Nature 282 1672446
1992 Cell adhesion molecules as targets for Hox genes: neural cell adhesion molecule promoter activity is modulated by cotransfection with Hox-2.5 and -2.4. Proceedings of the National Academy of Sciences of the United States of America 221 1347944
1991 Effects of retinoic acid excess on expression of Hox-2.9 and Krox-20 and on morphological segmentation in the hindbrain of mouse embryos. The EMBO journal 219 1915273
2006 HOXB7, a homeodomain protein, is overexpressed in breast cancer and confers epithelial-mesenchymal transition. Cancer research 175 17018609
1996 HOXB7 constitutively activates basic fibroblast growth factor in melanomas. Molecular and cellular biology 171 8756643
1990 Mouse Hox-2.2 specifies thoracic segmental identity in Drosophila embryos and larvae. Cell 163 1979525
1992 Neuroectodermal autonomy of Hox-2.9 expression revealed by rhombomere transpositions. Nature 151 1545869
1988 Characterization of a murine homeo box gene, Hox-2.6, related to the Drosophila Deformed gene. Genes & development 143 2463210
1989 Expression of Hox-2.4 homeobox gene directed by proviral insertion in a myeloid leukemia. Nucleic acids research 130 2564662
2001 HOXB7: a key factor for tumor-associated angiogenic switch. Cancer research 120 11522651
1992 Analysis of the murine Hox-2.7 gene: conserved alternative transcripts with differential distributions in the nervous system and the potential for shared regulatory regions. The EMBO journal 118 1582411
2010 MicroRNA miR-196a is a central regulator of HOX-B7 and BMP4 expression in malignant melanoma. Cellular and molecular life sciences : CMLS 113 20480203
1990 Hox-2.3 upstream sequences mediate lacZ expression in intermediate mesoderm derivatives of transgenic mice. Development (Cambridge, England) 105 1977573
2011 The HOXB7 protein renders breast cancer cells resistant to tamoxifen through activation of the EGFR pathway. Proceedings of the National Academy of Sciences of the United States of America 100 21690342
1991 The murine Hox-2 genes display dynamic dorsoventral patterns of expression during central nervous system development. Development (Cambridge, England) 100 1685115
1991 The expression of murine Hox-2 genes is dependent on the differentiation pathway and displays a collinear sensitivity to retinoic acid in F9 cells and Xenopus embryos. Nucleic acids research 99 1682879
1993 Conditional immortalization of mouse myelomonocytic, megakaryocytic and mast cell progenitors by the Hox-2.4 homeobox gene. The EMBO journal 97 8104786
2007 A role for the HOXB7 homeodomain protein in DNA repair. Cancer research 84 17308091
1998 Transduction of the SkBr3 breast carcinoma cell line with the HOXB7 gene induces bFGF expression, increases cell proliferation and reduces growth factor dependence. Oncogene 77 9681827
2015 HOXB7 Is an ERα Cofactor in the Activation of HER2 and Multiple ER Target Genes Leading to Endocrine Resistance. Cancer discovery 73 26180042
1987 Sequence analysis of the murine Hox-2.2, -2.3, and -2.4 homeo boxes: evolutionary and structural comparisons. Genomics 72 2891608
1991 The oncogenic potential of an activated Hox-2.4 homeobox gene in mouse fibroblasts. Molecular and cellular biology 68 1670897
2017 miR-196b-5p Regulates Colorectal Cancer Cell Migration and Metastases through Interaction with HOXB7 and GALNT5. Clinical cancer research : an official journal of the American Association for Cancer Research 67 28533224
1998 Analysis of Hoxa7/Hoxb7 mutants suggests periodicity in the generation of the different sets of vertebrae. Mechanisms of development 64 9784603
1989 Differential expression of human HOX-2 genes along the anterior-posterior axis in embryonic central nervous system. Differentiation; research in biological diversity 64 2570724
2008 Hoxb7 inhibits transgenic HER-2/neu-induced mouse mammary tumor onset but promotes progression and lung metastasis. Cancer research 62 18463397
1989 The developmental expression pattern of a new murine homeo box gene: Hox-2.5. Developmental biology 61 2567250
2014 HOXB7 promotes malignant progression by activating the TGFβ signaling pathway. Cancer research 60 25542862
1990 Expression of the murine homeobox-containing gene Hox-2.3 suggests multiple time-dependent and tissue-specific roles during development. Development (Cambridge, England) 60 1983116
2015 Mesenchymal progenitors aging highlights a miR-196 switch targeting HOXB7 as master regulator of proliferation and osteogenesis. Stem cells (Dayton, Ohio) 59 25428821
1999 Enforced expression of HOXB7 promotes hematopoietic stem cell proliferation and myeloid-restricted progenitor differentiation. Oncogene 57 10208421
2013 The abrogation of the HOXB7/PBX2 complex induces apoptosis in melanoma through the miR-221&222-c-FOS pathway. International journal of cancer 55 23400877
2012 HOXB7 promotes invasion and predicts survival in pancreatic adenocarcinoma. Cancer 55 22914903
1992 Ectopic expression of Hox-2.3 induces craniofacial and skeletal malformations in transgenic mice. Mechanisms of development 54 1362649
1993 Colinearity in the Xenopus laevis Hox-2 complex. Mechanisms of development 53 8095151
1993 Cooperative DNA binding of the human HoxB5 (Hox-2.1) protein is under redox regulation in vitro. Molecular and cellular biology 51 8101633
1988 Structure and expression of Hox-2.2, a murine homeobox-containing gene. Proceedings of the National Academy of Sciences of the United States of America 51 2899893
1999 CBP and histone deacetylase inhibition enhance the transactivation potential of the HOXB7 homeodomain-containing protein. Oncogene 50 10435624
1993 Proximal cis-acting elements cooperate to set Hoxb-7 (Hox-2.3) expression boundaries in transgenic mice. Development (Cambridge, England) 50 8104144
1998 Expression of Hoxa-1 and Hoxb-7 is regulated by extracellular matrix-dependent signals in mammary epithelial cells. Journal of cellular biochemistry 48 9620166
1990 The zebrafish homeobox gene hox-2.2: transcription unit, potential regulatory regions and in situ localization of transcripts. The EMBO journal 47 1968004
2010 HOXB7 expression by myeloma cells regulates their pro-angiogenic properties in multiple myeloma patients. Leukemia 45 21183939
1990 A yeast artificial chromosome containing the mouse homeobox cluster Hox-2. Proceedings of the National Academy of Sciences of the United States of America 45 1972280
2000 HOXB7 overexpression promotes differentiation of C3H10T1/2 cells to smooth muscle cells. Journal of cellular biochemistry 43 10842316
1992 Xenopus Hox-2 genes are expressed sequentially after the onset of gastrulation and are differentially inducible by retinoic acid. Development (Cambridge, England) 43 1363722
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1992 Inhibition of specific pathways of myeloid cell differentiation by an activated Hox-2.4 homeobox gene. Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research 41 1359901
2017 HOXB7 accelerates the malignant progression of hepatocellular carcinoma by promoting stemness and epithelial-mesenchymal transition. Journal of experimental & clinical cancer research : CR 40 28646927
2017 MiR-376c-3p regulates the proliferation, invasion, migration, cell cycle and apoptosis of human oral squamous cancer cells by suppressing HOXB7. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 39 28482289
1997 Lineage-specific regulation of hematopoiesis by HOX-B8 (HOX-2.4): inhibition of granulocytic differentiation and potentiation of monocytic differentiation. Blood 38 9292516
2001 Identification of novel functional regions important for the activity of HOXB7 in mammalian cells. Journal of immunology (Baltimore, Md. : 1950) 36 11290787
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2015 DNA methylation analysis of Homeobox genes implicates HOXB7 hypomethylation as risk factor for neural tube defects. Epigenetics 35 25565354
1992 Expression of selected human HOX-2 genes in B/T acute lymphoid leukemia and interleukin-2/interleukin-1 beta-stimulated natural killer lymphocytes. Blood 35 1351762
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1986 The murine Hox-2 cluster of homeo box containing genes maps distal on chromosome 11 near the tail-short (Ts) locus. Cytogenetics and cell genetics 32 2875852
2021 Silencing of hsa_circ_0009035 Suppresses Cervical Cancer Progression and Enhances Radiosensitivity through MicroRNA 889-3p-Dependent Regulation of HOXB7. Molecular and cellular biology 31 33782039
2015 Identification of several potential chromatin binding sites of HOXB7 and its downstream target genes in breast cancer. International journal of cancer 31 26014856
2013 HOXB7 mRNA is overexpressed in pancreatic ductal adenocarcinomas and its knockdown induces cell cycle arrest and apoptosis. BMC cancer 31 24088503
2020 LncRNA MAGI2-AS3 Overexpression Sensitizes Esophageal Cancer Cells to Irradiation Through Down-Regulation of HOXB7 via EZH2. Frontiers in cell and developmental biology 30 33330444
2018 HOXB7 overexpression in lung cancer is a hallmark of acquired stem-like phenotype. Oncogene 30 29576613
2018 Circular RNA hsa_circ_0074362 Promotes Glioma Cell Proliferation, Migration, and Invasion by Attenuating the Inhibition of miR-1236-3p on HOXB7 Expression. DNA and cell biology 30 30388035
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2019 HOXB7 mediates cisplatin resistance in esophageal squamous cell carcinoma through involvement of DNA damage repair. Thoracic cancer 28 31568655
1999 IkappaB-alpha enhances transactivation by the HOXB7 homeodomain-containing protein. The Journal of biological chemistry 26 10026139
2018 Specific knockdown of HOXB7 inhibits cutaneous squamous cell carcinoma cell migration and invasion while inducing apoptosis via the Wnt/β-catenin signaling pathway. American journal of physiology. Cell physiology 25 30067384
2016 The roles of HOXB7 in promoting migration, invasion, and anti-apoptosis in gastric cancer. Journal of gastroenterology and hepatology 25 26968988
2014 Levels of HOXB7 and miR-337 in pancreatic ductal adenocarcinoma patients. Diagnostic pathology 25 24641834
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1987 The mouse Hox2.3 homeobox-containing gene: regulation in differentiating pluripotent stem cells and expression pattern in embryos. Differentiation; research in biological diversity 25 2892751
2017 The transcription factor HOXB7 regulates ERK kinase activity and thereby stimulates the motility and invasiveness of pancreatic cancer cells. The Journal of biological chemistry 24 28912272
2014 miR-337 regulates the proliferation and invasion in pancreatic ductal adenocarcinoma by targeting HOXB7. Diagnostic pathology 24 25183455
1988 In situ hybridization patterns of zebrafish homeobox genes homologous to Hox-2.1 and En-2 of mouse. Biochemical and biophysical research communications 24 2904810
2020 CircRNA hsa_circ_0070934 functions as a competitive endogenous RNA to regulate HOXB7 expression by sponging miR‑1236‑3p in cutaneous squamous cell carcinoma. International journal of oncology 23 32626939
2008 Oncogenic HoxB7 requires TALE cofactors and is inactivated by a dominant-negative Pbx1 mutant in a cell-specific manner. Cancer letters 22 18378073
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2015 Upregulation of HOXB7 promotes the tumorigenesis and progression of gastric cancer and correlates with clinical characteristics. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 20 26307396
2012 Detection of IGF2BP3, HOXB7, and NEK2 mRNA expression in brush cytology specimens as a new diagnostic tool in patients with biliary strictures. PloS one 20 22879911
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2020 Psoralen Suppresses Cisplatin-Mediated Resistance and Induces Apoptosis of Gastric Adenocarcinoma by Disruption of the miR196a-HOXB7-HER2 Axis. Cancer management and research 14 32368152
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