Affinage

FOXN3

Forkhead box protein N3 · UniProt O00409

Length
490 aa
Mass
53.8 kDa
Annotated
2026-04-28
46 papers in source corpus 23 papers cited in narrative 23 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

FOXN3 is a forkhead-family transcriptional repressor that suppresses diverse gene programs—including cell proliferation, glucose metabolism, inflammatory signaling, fibrotic responses, and ciliogenesis—by recruiting co-repressor complexes and modulating chromatin state. Structurally, its DNA-binding domain recognizes both canonical FKH (RYAAAYA) and distinct FHL (GACGC) motifs using the same protein residues but exploiting different DNA shapes (PMID:30826165), and it exerts repression through interaction with the SIN3A/HDAC1/HDAC2 complex, SKIP/NCoA-62, and the lncRNA NEAT1 (PMID:28805661, PMID:16951149, PMID:16102918). FOXN3 stability is controlled by phosphorylation-triggered proteasomal degradation: p38 phosphorylates S83/S85 to release FOXN3 from hnRNPU (thereby activating NF-κB signaling), NEK6 phosphorylates S412/S416 to promote FOXN3 loss (enabling Smad4-dependent fibrotic transcription), and PARP1 stabilizes FOXN3 by blocking p38-mediated phosphorylation (PMID:36794705, PMID:39984467, PMID:41481720). In addition to its roles in hepatic gluconeogenesis via MYC repression (PMID:27292639, PMID:29996093), β-catenin/TCF inhibition in colon cancer (PMID:28039460), direct transcriptional repression of targets such as PIM2, E2F5, and EP300 (PMID:24403608, PMID:27259277, PMID:39607349), and suppression of aberrant ciliogenesis in nonphotoreceptor retinal neurons through interaction with Rfx3 via an LXXLXWL motif (PMID:40663603, PMID:41766387), FOXN3 loss-of-function in mice causes craniofacial defects, growth retardation, and partial lethality (PMID:20691664).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 2005 Medium

    Establishing FOXN3 as a transcriptional repressor and identifying its first co-factor: FOXN3 was known to participate in the S-phase DNA damage checkpoint, but its mechanism of transcriptional regulation was unknown; this work showed it represses transcription via its C-terminus and physically interacts with the co-regulator SKIP/NCoA-62.

    Evidence Reporter gene assays, cytoplasmic two-hybrid, and Co-IP in mammalian cells

    PMID:16102918

    Open questions at the time
    • Endogenous target genes were not identified
    • Functional consequence of SKIP interaction on chromatin not tested
    • Only one interacting partner identified
  2. 2006 High

    Linking FOXN3 to the SIN3A/HDAC repressor complex and a menin-dependent DNA damage checkpoint: it was unclear how FOXN3 represses transcription at chromatin level; this study showed FOXN3 assembles into a complex with mSin3a, HDAC1, and HDAC2, and that it interacts with menin to restore S-phase checkpoint arrest in MEN1-mutant Drosophila.

    Evidence Genetic screen in Drosophila, Co-IP of human proteins, epistasis rescue of MEN1 mutants

    PMID:16951149

    Open questions at the time
    • Direct enzymatic contribution of HDACs to FOXN3-mediated repression not dissected
    • Human checkpoint function not validated
  3. 2010 Medium

    Demonstrating a developmental requirement for Foxn3: whether FOXN3 had organismal-level functions was unknown; Foxn3 knockout mice showed craniofacial defects, eye abnormalities, growth retardation, and partial lethality, establishing an essential developmental role.

    Evidence Gene knockout mouse model with histological and gene expression analysis

    PMID:20691664

    Open questions at the time
    • Tissue-specific versus systemic contributions not resolved
    • Direct transcriptional targets in craniofacial tissues not identified
  4. 2014 High

    Identifying PIM2 as a direct FOXN3 target linking transcriptional repression to growth suppression: how FOXN3 inhibited proliferation at the molecular level was unclear; ChIP demonstrated direct FOXN3 binding at the PIM2 promoter, and PIM2 rescue partially reversed growth arrest, connecting FOXN3 repression to protein synthesis control via 4EBP1.

    Evidence ChIP, shRNA knockdown, overexpression rescue, protein synthesis assays in tumor cell lines

    PMID:24403608

    Open questions at the time
    • Genome-wide binding landscape not yet mapped
    • Contribution of SIN3A/HDAC at PIM2 promoter not tested
  5. 2016 High

    Establishing FOXN3 as a regulator of hepatic glucose metabolism via MYC repression: the physiological functions of FOXN3 beyond cancer were unexplored; this work showed FOXN3 binds MYC loci, suppresses MYC expression, and controls gluconeogenic gene programs, with zebrafish genetic models demonstrating effects on blood glucose.

    Evidence Transgenic and knockout zebrafish, DNA binding assays, gene expression in human hepatocytes, glucose measurements

    PMID:27292639

    Open questions at the time
    • Mammalian hepatic loss-of-function not yet performed
    • Chromatin mechanism at MYC locus not dissected
  6. 2017 High

    Revealing a lncRNA-dependent recruitment mechanism for FOXN3 repression and a new tumor-suppressive axis: how FOXN3 was recruited to specific gene sets was unclear; NEAT1 was shown to be required for FOXN3 association with SIN3A, and this complex repressed GATA3 to promote EMT in breast cancer, while also forming a negative-feedback loop with ERα.

    Evidence RIP-seq, ChIP-seq, Co-IP, in vivo metastasis assays in ER+ breast cancer models

    PMID:28805661

    Open questions at the time
    • Whether NEAT1 dependence applies beyond ER+ breast cancer not tested
    • Structural basis of NEAT1-FOXN3 interaction unknown
  7. 2017 Medium

    Demonstrating FOXN3 directly inhibits β-catenin/TCF signaling by binding β-catenin: how FOXN3 suppressed Wnt pathway-driven cancers was unknown; Co-IP showed FOXN3 binds β-catenin and blocks its interaction with TCF4 in colon cancer cells.

    Evidence Co-IP, gain/loss-of-function, β-catenin/TCF reporter, in vivo metastasis model

    PMID:28039460

    Open questions at the time
    • Whether this interaction occurs on chromatin or in the nucleoplasm not determined
    • β-catenin binding domain on FOXN3 not mapped
  8. 2018 High

    Defining a glucagon–FOXN3 reciprocal axis controlling fasting glucose and α-cell mass: whether FOXN3 was itself hormonally regulated was unknown; glucagon was shown to reduce hepatic FOXN3, while liver FOXN3 overexpression increased pancreatic α-cell mass, establishing a liver–pancreas feedback circuit.

    Evidence Glucagon injection in mice/zebrafish, foxn3 loss-of-function mutants, liver-limited overexpression, endocrine measurements

    PMID:29996093

    Open questions at the time
    • Mechanism of FOXN3 downregulation by glucagon not determined
    • Signal mediating liver-to-α-cell communication not identified
  9. 2019 High

    Solving the structural basis for FOXN3 bispecific DNA recognition: how a single forkhead domain binds two dissimilar DNA motifs was unknown; co-crystal structures revealed the same amino acids contact both FKH and FHL motifs, with specificity arising from different DNA shapes.

    Evidence X-ray co-crystal structures of FoxN3 DBD bound to FKH and FHL motifs

    PMID:30826165

    Open questions at the time
    • How bispecific recognition is regulated in vivo not known
    • Full-length FOXN3 structure not determined
  10. 2023 High

    Uncovering the phosphorylation-dependent mechanism linking FOXN3 to NF-κB suppression: the post-translational regulation of FOXN3 was poorly understood; p38 was shown to directly phosphorylate FOXN3 at S83/S85, causing dissociation from hnRNPU and proteasomal degradation, while unphosphorylated FOXN3 competes with IκBα for hnRNPU binding to suppress NF-κB.

    Evidence In vitro kinase assay, site-directed mutagenesis, Co-IP, genetic ablation mouse models, NF-κB reporter assays

    PMID:36794705

    Open questions at the time
    • Whether hnRNPU scaffolding is the sole route to NF-κB regulation not tested
    • Tissue specificity of this axis not established
  11. 2025 High

    Establishing FOXN3 as a suppressor of aberrant ciliogenesis in the retina: why nonphotoreceptor retinal neurons lack cilia despite expressing ciliary pathway components was unknown; retina-specific Foxn3 CKO caused ectopic ciliary gene expression and abnormal cilia in bipolar/amacrine cells, with CUT&RUN confirming direct promoter binding at ciliary genes and Foxj1/Rfx targets.

    Evidence Conditional knockout mice, electroretinogram, scRNA-seq, CUT&RUN, transcription assays

    PMID:40663603

    Open questions at the time
    • Whether FOXN3 repression of cilia genes operates in non-retinal neurons unknown
    • Epigenetic mechanism at ciliary promoters not dissected
  12. 2025 High

    Defining a NEK6–FOXN3–Smad4 axis controlling pulmonary fibrosis: how pro-fibrotic signals overcome FOXN3 repression of TGF-β targets was unclear; NEK6 phosphorylates FOXN3 at S412/S416 for degradation, and FOXN3 normally promotes β-TrCP-mediated Smad4 ubiquitination to disassemble the Smad complex from chromatin.

    Evidence In vitro kinase assay, mutagenesis, Co-IP, ChIP, ubiquitination assay, conditional knockout mice

    PMID:39984467

    Open questions at the time
    • Whether the β-TrCP/Smad4 ubiquitination pathway operates outside lung not tested
    • Direct structural basis of FOXN3-Smad4 interaction unknown
  13. 2026 High

    Identifying the LXXLXWL motif as the basis for FOXN3–Rfx3 interaction at ciliary gene promoters: how FOXN3 is recruited to ciliary genes was mechanistically undefined; mutagenesis showed a conserved hydrophobic motif in FOXN3 mediates binding to the Rfx3 dimerization domain, and CUT&RUN confirmed co-occupancy at ciliary gene promoters.

    Evidence CUT&RUN, motif mutagenesis, AlphaFold 3 prediction validated by mutagenesis, transcriptional reporter assays

    PMID:41766387

    Open questions at the time
    • Whether the motif also mediates interaction with other Rfx family members not tested
    • No experimental structure of the FOXN3-Rfx3 complex
  14. 2026 High

    Defining PARP1 as a stabilizer of FOXN3 that forms a feedback loop with p38/Smad signaling: what prevents constitutive FOXN3 degradation was unknown; PARP1 binds FOXN3 and blocks p38 phosphorylation, while the PARP1/FOXN3 complex transcriptionally represses p38, creating a positive feedback loop that suppresses fibrosis.

    Evidence Co-IP, lung-specific PARP1 knockout, conditional FOXN3 overexpression rescue, ChIP, gene expression analysis

    PMID:41481720

    Open questions at the time
    • Whether PARP1 enzymatic activity (PARylation) is required or only scaffolding not resolved
    • Applicability beyond lung tissue not tested

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include: the genome-wide landscape of FOXN3 binding across tissues; how bispecific FKH/FHL recognition is functionally partitioned at endogenous targets; whether SIN3A/HDAC recruitment is universal or context-dependent; the full structural basis for FOXN3 interactions with β-catenin, Smad4, and hnRNPU; and whether the PARP1-FOXN3-p38 feedback loop operates beyond pulmonary tissue.
  • No genome-wide FOXN3 binding atlas across multiple tissues
  • Full-length FOXN3 structure not solved
  • Tissue-specific versus universal co-repressor usage not resolved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 10 GO:0003677 DNA binding 5
Localization
GO:0005634 nucleus 4
Pathway
R-HSA-1266738 Developmental Biology 3 R-HSA-162582 Signal Transduction 3 R-HSA-4839726 Chromatin organization 3
Partners
CTNNB1HDAC1HDAC2HNRNPUMEN1RFX3SIN3ASKIP
Complex memberships
FOXN3-NEAT1-SIN3A complexPARP1-FOXN3 complexSIN3A/HDAC1/HDAC2 repressor complex

Evidence

Reading pass · 23 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2017 FOXN3 forms a repressor complex with the lncRNA NEAT1 and the SIN3A complex in ER+ breast cancer cells. NEAT1 (estrogen-inducible) is required for FOXN3 interactions with the SIN3A complex. This FOXN3-NEAT1-SIN3A complex represses target genes including GATA3, promotes EMT and invasion, and also transrepresses ERα itself, forming a negative-feedback loop. RNA immunoprecipitation-coupled high-throughput sequencing (RIP-seq), ChIP-Seq, co-immunoprecipitation, in vitro and in vivo functional assays The Journal of clinical investigation High 28805661
2005 FOXN3 (CHES1) functions as a transcriptional repressor via its carboxyl terminus, and interacts with Ski-interacting protein (SKIP/NCoA-62), a transcriptional co-regulator associated with repressor complexes. FOXN3 binds the final 66 hydrophobic residues of SKIP, defining a new protein-protein interaction domain. Reporter gene transcription assay, cytoplasmic two-hybrid screen, co-immunoprecipitation in mammalian cells Gene Medium 16102918
2006 FOXN3 (CHES1) interacts biochemically with human menin (MEN1 protein) via the COOH terminus of menin (codons 428–610), and is a component of a transcriptional repressor complex including mSin3a, HDAC1, and HDAC2. Overexpression of CHES1 restored S-phase checkpoint arrest and viability of MEN1 mutant flies after ionizing radiation, placing FOXN3 in an S-phase DNA damage checkpoint pathway downstream of or parallel to menin. Genetic screen in Drosophila, co-immunoprecipitation of human proteins, epistasis by overexpression rescue Cancer research High 16951149
2019 Co-crystal structures of the FoxN3 DNA-binding domain bound to both the canonical forkhead (FKH) motif (RYAAAYA) and the distinct forkhead-like (FHL) motif (GACGC) reveal that FoxN3 adopts a similar protein conformation to contact both motifs using the same amino acids, but the DNA shape differs between the two complexes, providing the structural basis for bispecific DNA recognition. Co-crystal structure determination (X-ray crystallography), protein-DNA binding assays Molecular cell High 30826165
2014 FOXN3 (CHES1) represses cell proliferation and protein synthesis in tumor cell lines by directly binding the promoter of PIM2 (a kinase regulating protein biosynthesis) and repressing its expression, leading to decreased phosphorylation of PIM2 target 4EBP1. Overexpression of PIM2 or eIF4E partially reverses the antiproliferative effect of FOXN3. The forkhead DNA-binding domain and nuclear localization are required for this growth suppression. ChIP (direct promoter binding), shRNA knockdown, overexpression rescue, protein synthesis assays, proliferation assays Molecular biology of the cell High 24403608
2016 FOXN3 inhibits hepatocellular carcinoma cell proliferation in vitro and in vivo by transcriptionally repressing E2F5 — it binds the E2F5 promoter and reduces E2F5 mRNA and protein expression. Luciferase promoter activity assay, qPCR, Western blot, in vitro proliferation assays, in vivo xenograft Oncotarget Medium 27259277
2016 FOXN3 is a transcriptional repressor of hepatic gluconeogenic genes. Its protein and transcript are downregulated during fasting in rat liver and human HepG2 cells. Overexpression of zebrafish foxn3 or human FOXN3 in zebrafish liver increases gluconeogenic gene expression, whole-larval free glucose, and adult fasting blood glucose, and decreases glycolytic gene expression. FOXN3 binds DNA sequences in the MYC/mycb loci and suppresses MYC expression, which normally stimulates glucose-utilization enzymes. Transgenic zebrafish overexpression, knockout zebrafish, DNA binding assay, gene expression analysis in primary human hepatocytes, glucose/gluconeogenesis measurements Cell reports High 27292639
2018 Liver FOXN3 and glucagon form a reciprocal regulatory axis controlling fasting glucose: glucagon decreases liver Foxn3 protein and transcript, while liver-limited overexpression of foxn3 increases pancreatic α cell mass. Zebrafish foxn3 loss-of-function mutants have decreased fasting blood glucose, blood glucagon, liver gluconeogenic gene expression, and α cell mass. Glucagon injection in mice and adult zebrafish, zebrafish foxn3 loss-of-function mutants, liver-limited transgenic overexpression, glucose/glucagon measurement, α cell mass quantification Cell reports High 29996093
2023 FOXN3 is directly phosphorylated by p38 kinase at S83 and S85 residues. This phosphorylation induces FOXN3 dissociation from hnRNPU and subsequent proteasomal degradation. In unphosphorylated form, FOXN3 competes with IκBα for binding to hnRNPU, thereby blocking β-TrCP-mediated IκBα degradation and inactivating NF-κB signaling. hnRNPU is required for p38-mediated FOXN3 phosphorylation. In vitro kinase assay (phosphorylation at specific residues), Co-immunoprecipitation, site-directed mutagenesis (S83A/S85A), proteasome inhibitor assays, genetic ablation mouse models, NF-κB reporter assays Nucleic acids research High 36794705
2025 NEK6 kinase phosphorylates FOXN3 at S412 and S416 in response to pro-fibrotic stimuli, leading to FOXN3 proteasomal degradation. FOXN3 normally suppresses pulmonary fibrosis by facilitating Smad4 ubiquitination, which disrupts the Smad2/3/4 complex's association with chromatin and abolishes Smad transcriptional responses. Loss of FOXN3 prevents β-TrCP-mediated Smad4 ubiquitination, stabilizes the Smad complex at response elements, and promotes fibrosis. In vitro kinase assay, site-directed mutagenesis, Co-immunoprecipitation, ChIP, ubiquitination assay, conditional knockout mice, gene overexpression, clinical sample correlation Nature communications High 39984467
2026 PARP1 binds FOXN3 and stabilizes it by blocking p38-mediated phosphorylation and subsequent degradation. Lung-specific PARP1 knockout reduces FOXN3 abundance and promotes pulmonary fibrosis; conditional FOXN3 overexpression rescues this by impeding Smad signaling. The PARP1/FOXN3 complex transcriptionally represses p38 (a Smad response gene), forming a feedback loop: loss of PARP1 or FOXN3 increases p38, which further degrades FOXN3 and activates Smad signaling. Co-immunoprecipitation (PARP1-FOXN3 interaction), conditional knockout mice (lung-specific PARP1 KO), conditional FOXN3 overexpression rescue, ChIP, gene expression analysis Science advances High 41481720
2017 FOXN3 binds β-catenin directly and inhibits β-catenin/TCF signaling in colon cancer cells by blocking the interaction between β-catenin and TCF4. Loss of FOXN3 activates β-catenin/TCF signaling and promotes colon cancer cell growth, migration, and invasion. Co-immunoprecipitation (FOXN3-β-catenin interaction), gain/loss-of-function assays, in vivo metastasis model, β-catenin/TCF reporter assay Oncotarget Medium 28039460
2019 FOXN3 controls liver gluconeogenic substrate selection: hepatic Foxn3 knockdown (via AAV-shRNA) decreases fasting glucose and increases Myc expression without altering fasting glucagon or insulin; it blunts pyruvate and glutamine tolerance and modulates expression of amino acid transporters and catabolic enzymes, indicating FOXN3 regulates substrate preference for gluconeogenesis. AAV-mediated shRNA knockdown in adult mice, dynamic endocrine tests (glucose/insulin/pyruvate/glutamine tolerance tests, glucagon challenge), hepatic gene expression profiling Physiological reports Medium 31552709
2010 Foxn3 is required for craniofacial development in mice: Foxn3 mutant mice display partial embryonic and postnatal lethality, growth retardation, eye formation defects, dental anomalies, and craniofacial defects. Foxn3 mutant tissues show defective expression of distinct osteogenic genes. Mutant mouse model (gene knockout), histological and developmental analysis, gene expression in mutant tissues Biochemical and biophysical research communications Medium 20691664
2018 FOXN3 transcriptionally regulates SIRT6 in osteosarcoma: ChIP and luciferase reporter assays demonstrated direct binding of FOXN3 to the SIRT6 promoter. FOXN3 also regulates MMP-9 secretion via SIRT6. Chromatin immunoprecipitation (ChIP), quantitative ChIP, luciferase reporter assay, functional invasion/migration assays Oncology reports Medium 30483801
2022 Foxn3 regulates retinal amacrine cell formation: inhibition of Foxn3 by RNAi or CRISPR in the developing mouse retina increased amacrine cell formation and reduced bipolar cell formation. Foxn3 overexpression inhibited amacrine cell formation. Foxn3 mRNA was identified as a retinal target of miR-216b by Argonaute PAR-CLIP. Argonaute PAR-CLIP, RNAi knockdown, CRISPR disruption, Foxn3 overexpression in retinal explants, cell-type quantification Development (Cambridge, England) Medium 34919141
2025 Foxn3 is essential for suppressing aberrant ciliogenesis in nonphotoreceptor retinal neurons: retina-specific Foxn3 conditional knockout mice show ectopic ciliary gene expression and abnormal ciliogenesis in bipolar and amacrine cells, impaired electroretinogram b-wave amplitudes, without affecting retinal cell specification. Foxn3 directly binds and represses promoters of ciliary genes and their transactivators Foxj1 and Rfx family members, as shown by CUT&RUN and transcription assays. Conditional knockout mice (retina-specific Foxn3 CKO), electroretinogram, single-cell RNA sequencing, CUT&RUN (chromatin profiling), transcription assays, immunostaining Proceedings of the National Academy of Sciences of the United States of America High 40663603
2026 Foxn3 interacts with Rfx3 via a short hydrophobic motif (LXXLXWL) shared with Foxn4 and Foxj1. This motif is required for association with the Rfx3 dimerization domain (supported by AlphaFold 3 prediction and validated by Rfx3 mutations disrupting association) and is necessary for transcriptional repression of cilia genes by Foxn3. Foxn3 and Rfx3 co-occupy promoters of cilia-related genes as shown by CUT&RUN. CUT&RUN chromatin profiling, protein interaction assays with motif mutagenesis, AlphaFold 3 structural prediction validated by mutagenesis, transcriptional reporter assays Development (Cambridge, England) High 41766387
2021 FOXN3 inhibits glioma cell proliferation and invasion by inactivating the AKT/MDM2/p53 signaling pathway: FOXN3 overexpression suppresses AKT/MDM2/p53 activation, while FOXN3 knockdown facilitates it in glioma cells. Gain/loss-of-function in glioma cell lines, Western blot for pathway components, xenograft tumor assay Aging Low 34511432
2024 FOXN3 (CHES1) transcriptionally represses AKR1B10 in pancreatic cancer cells; label-free quantitative proteomics identified AKR1B10 as a downstream target of CHES1, and CHES1 modulates cellular senescence and gemcitabine sensitivity through AKR1B10. Label-free quantitative proteomics, functional senescence assays, ChIP (implied), proliferation and invasion assays, pharmacological inhibition Biochimica et biophysica acta. Molecular basis of disease Medium 38718846
2023 FOXN3 directly binds the RPS15A promoter (at positions -1588/-1581 and -1476/-1467) and inhibits its transcriptional expression in ovarian cancer cells, suppressing proliferation, migration, invasion, and angiogenesis. Overexpression of RPS15A reverses FOXN3-mediated inhibition. Dual-luciferase assay, ChIP, cell functional assays, in vivo xenograft Human cell Medium 37016167
2024 FOXN3 binds the promoter region of FSIP1 (Fibrous Sheath Interacting Protein 1) in melanoma cells, regulating FSIP1 expression and autophagic activity; differential FOXN3 subcellular localization was observed between Vemurafenib-sensitive and -resistant melanoma cells. Chromatin immunoprecipitation, immunofluorescence (subcellular localization), functional proliferation/invasion assays Clinical, cosmetic and investigational dermatology Low 39530064
2024 FOXN3 transcriptionally represses EP300 in colorectal cancer cells by binding the EP300 promoter, thereby reducing H3K27ac enrichment at the SOX12 promoter and suppressing SOX12 expression; this inhibits CRC cell stemness and Wnt/β-catenin signaling. EP300 overexpression reverses the inhibitory effect of FOXN3. ChIP (H3K27ac and FOXN3 binding to EP300 and SOX12 promoters), dual-luciferase reporter, functional stemness and proliferation assays, in vivo tumor formation Molecular carcinogenesis Medium 39607349

Source papers

Stage 0 corpus · 46 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2017 The FOXN3-NEAT1-SIN3A repressor complex promotes progression of hormonally responsive breast cancer. The Journal of clinical investigation 169 28805661
2005 Identification of differentially expressed genes in oral squamous cell carcinoma (OSCC): overexpression of NPM, CDK1 and NDRG1 and underexpression of CHES1. International journal of cancer 85 15645429
2006 Multiple endocrine neoplasia type 1 interacts with forkhead transcription factor CHES1 in DNA damage response. Cancer research 67 16951149
2014 Higher risk of aggressive pancreatic neuroendocrine tumors in MEN1 patients with MEN1 mutations affecting the CHES1 interacting MENIN domain. The Journal of clinical endocrinology and metabolism 52 25210877
2016 The transcription factor FOXN3 inhibits cell proliferation by downregulating E2F5 expression in hepatocellular carcinoma cells. Oncotarget 51 27259277
2005 CHES1/FOXN3 interacts with Ski-interacting protein and acts as a transcriptional repressor. Gene 44 16102918
2010 Foxn3 is essential for craniofacial development in mice and a putative candidate involved in human congenital craniofacial defects. Biochemical and biophysical research communications 43 20691664
2019 Bispecific Forkhead Transcription Factor FoxN3 Recognizes Two Distinct Motifs with Different DNA Shapes. Molecular cell 40 30826165
2023 p38-mediated FOXN3 phosphorylation modulates lung inflammation and injury through the NF-κB signaling pathway. Nucleic acids research 39 36794705
2017 Loss of FOXN3 in colon cancer activates beta-catenin/TCF signaling and promotes the growth and migration of cancer cells. Oncotarget 34 28039460
2014 CHES1/FOXN3 regulates cell proliferation by repressing PIM2 and protein biosynthesis. Molecular biology of the cell 33 24403608
2016 FOXN3 Regulates Hepatic Glucose Utilization. Cell reports 31 27292639
2019 Recent Advances in Understanding FOXN3 in Breast Cancer, and Other Malignancies. Frontiers in oncology 28 31214487
2025 Phosphorylation of FOXN3 by NEK6 promotes pulmonary fibrosis through Smad signaling. Nature communications 22 39984467
2020 FOXN3 suppresses the growth and invasion of papillary thyroid cancer through the inactivation of Wnt/β-catenin pathway. Molecular and cellular endocrinology 22 32619584
2019 MicroRNA-378 regulates epithelial-mesenchymal transition and metastasis of melanoma by inhibiting FOXN3 expression through the Wnt/β-catenin pathway. Cell biology international 20 29972255
2011 Downregulation of Ches1 and other novel genes in oral cancer cells chronically exposed to areca nut extract. Head & neck 20 20848451
2020 MicroRNA-574-5p directly targets FOXN3 to mediate thyroid cancer progression via Wnt/β-catenin signaling pathway. Pathology, research and practice 17 32284251
2020 miR-574-5p Targets FOXN3 to Regulate the Invasion of Nasopharyngeal Carcinoma Cells via Wnt/β-Catenin Pathway. Technology in cancer research & treatment 15 33317407
2019 miR-611 promotes the proliferation, migration and invasion of tongue squamous cell carcinoma cells by targeting FOXN3. Oral diseases 15 31419344
2021 FOXN3 inhibits cell proliferation and invasion via modulating the AKT/MDM2/p53 axis in human glioma. Aging 14 34511432
2018 A Hepatocyte FOXN3-α Cell Glucagon Axis Regulates Fasting Glucose. Cell reports 13 29996093
2021 MicroRNA-182 promotes epithelial-mesenchymal transition by targeting FOXN3 in gallbladder cancer. Oncology letters 10 33574939
2019 Novel tumor-suppressor FOXN3 is downregulated in adult acute myeloid leukemia. Oncology letters 10 31423219
2019 FOXN3 controls liver glucose metabolism by regulating gluconeogenic substrate selection. Physiological reports 10 31552709
2018 FOXN3 is downregulated in osteosarcoma and transcriptionally regulates SIRT6, and suppresses migration and invasion in osteosarcoma. Oncology reports 10 30483801
2024 CHES1 modulated tumorigenesis and senescence of pancreas cancer cells through repressing AKR1B10. Biochimica et biophysica acta. Molecular basis of disease 8 38718846
2024 MiR-135b-5p promotes cetuximab resistance in colorectal cancer by regulating FOXN3. Cancer biology & therapy 7 38967961
2022 Regulation of retinal amacrine cell generation by miR-216b and Foxn3. Development (Cambridge, England) 6 34919141
2019 MicroRNA-378 promotes the malignant progression of oral squamous cell carcinoma by mediating FOXN3. European review for medical and pharmacological sciences 6 31364120
2023 FOXN3 inhibits the progression of ovarian cancer through negatively regulating the expression of RPS15A. Human cell 5 37016167
2021 Up-regulation of FOXN3-AS1 in invasive ductal carcinoma of breast cancer patients. Heliyon 5 34703931
2019 FoxN3 is necessary for the development of the interatrial septum, the ventricular trabeculae and the muscles at the head/trunk interface in the African clawed frog, Xenopus laevis (Lissamphibia: Anura: Pipidae). Developmental dynamics : an official publication of the American Association of Anatomists 5 30859697
2019 FOXN3 hyperglycemic risk allele and insulin sensitivity in humans. BMJ open diabetes research & care 5 31543974
2022 FOXN3 Expression Regulated by miR-299-5p Inhibiting the Proliferation, Migration and Invasion of Oral Squamous Cell Carcinoma Cells. Protein and peptide letters 4 35975858
2022 MAGI2-AS3 restrains proliferation, glycolysis, and triggers apoptosis in acute lymphoblastic leukemia via regulating miR-452-5p/FOXN3 pathway. Iranian journal of basic medical sciences 3 35656441
2025 Foxn3 is part of a transcriptional network that regulates primary cilia in the developing retina. bioRxiv : the preprint server for biology 2 39554069
2025 Foxn3 is required to suppress aberrant ciliogenesis in nonphotoreceptor retinal neurons. Proceedings of the National Academy of Sciences of the United States of America 2 40663603
2024 FOXN3 Downregulation in Colorectal Cancer Enhances Tumor Cell Stemness by Promoting EP300-Mediated Epigenetic Upregulation of SOX12. Molecular carcinogenesis 2 39607349
2026 Foxn3 is part of a transcriptional network that regulates primary cilia in the developing retina. Development (Cambridge, England) 1 41766387
2026 PARP1 stabilizes FOXN3 to suppress pulmonary fibrosis through p38-related feedback regulation. Science advances 0 41481720
2026 Crosstalk Between FOXN3 and E2F5 Reveals a Novel Tumor Suppressive Pathway in Acute Myeloid Leukemia via MAPK Signaling: Implications for Potential Future Targeted Therapy. Blood and lymphatic cancer : targets and therapy 0 41908971
2025 Clinical significance of FOXN3 expression in Indian breast cancer patients. Scientific reports 0 40251258
2025 Cigarette smoking combines with genetic variants to regulate FOXN3 and associate with bladder cancer risk. Archives of toxicology 0 41361116
2024 Correlation between FOXN3-SIN3A complex expression in peripheral blood and non-syndromic cleft lip and palate in Xinjiang. Hua xi kou qiang yi xue za zhi = Huaxi kouqiang yixue zazhi = West China journal of stomatology 0 39049650
2024 FOXN3 Regulates Autophagic Activity to Suppress Drug Resistance in Melanoma Cells. Clinical, cosmetic and investigational dermatology 0 39530064