Affinage

FOXO6

Forkhead box protein O6 · UniProt A8MYZ6

Length
492 aa
Mass
50.6 kDa
Annotated
2026-04-28
60 papers in source corpus 32 papers cited in narrative 31 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

FOXO6 is a forkhead box transcription factor that functions as a nuclear integrator of insulin/PI3K/Akt signaling across metabolic, neural, and developmental programs. Unlike other FoxO family members, FOXO6 lacks the C-terminal PKB phosphorylation motif required for classical nuclear export; instead, Akt-mediated phosphorylation at Thr26 and Ser184 disables its DNA-binding and transcriptional activity while it remains nuclear (PMID:12857750, PMID:15987244). In the liver, FOXO6 directly activates gluconeogenic genes (PEPCK, G6Pase), lipid-regulatory targets (MTP, ApoC3, TXNIP), and inflammatory mediators (IL-1β), and physically interacts with PPARγ, PPARα, and CHOP to promote lipogenesis, suppress β-oxidation, and drive NLRP3 inflammasome activation, such that FOXO6 knockout attenuates diet-induced hepatic steatosis, hyperglycemia, and inflammation (PMID:21940782, PMID:24437489, PMID:25944898, PMID:38441531, PMID:32639626, PMID:39198274, PMID:38417829). In the brain, FOXO6 regulates synaptic gene programs including Plxna4 to maintain dendritic spine density and hippocampal memory consolidation, and in craniofacial tissues it activates Lats1 to engage Hippo signaling and restrain postnatal growth (PMID:23222102, PMID:27791111, PMID:30286078).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 2003 High

    Identification of FOXO6 as a novel FoxO family member resolved how the FoxO subfamily diversifies its nuclear-cytoplasmic regulation: FOXO6 lacks the C-terminal PKB phosphorylation site, making it predominantly nuclear even after growth factor stimulation.

    Evidence GFP-fusion transfection, chimeric protein analysis, PI3K/PKB pathway modulation, and subcellular localization imaging

    PMID:12857750

    Open questions at the time
    • Post-translational regulation beyond PKB phosphorylation not yet explored
    • Endogenous tissue expression pattern not characterized
  2. 2005 High

    Defining how insulin/PI3K/Akt controls FOXO6 without nuclear export established a novel regulatory paradigm: Thr26 phosphorylation acts as a growth factor sensor while Ser184 phosphorylation directly impairs DNA binding, together silencing FOXO6 transcriptional activity in situ.

    Evidence Site-directed mutagenesis of Thr26 and Ser184 combined with transcriptional reporter and DNA-binding assays

    PMID:15987244

    Open questions at the time
    • Whether additional kinases target these or other sites not tested
    • Crystal structure of phosphorylated FOXO6 forkhead domain unavailable
  3. 2011 High

    Linking FOXO6 to hepatic gluconeogenesis established its first in vivo metabolic function: gain-of-function augments glucose production and fasting blood glucose, while hepatic loss-of-function suppresses gluconeogenesis, confirming FOXO6 as a non-redundant gluconeogenic driver.

    Evidence Transgenic and knockout mouse models, adenoviral overexpression in liver, primary hepatocyte glucose production assays

    PMID:21940782

    Open questions at the time
    • Relative contribution of FOXO6 versus FoxO1 to hepatic gluconeogenesis not quantitatively resolved
    • Direct target gene ChIP evidence for PEPCK/G6Pase promoters not yet shown
  4. 2012 High

    Demonstrating that FOXO6 is required for hippocampal memory consolidation and dendritic spine density revealed a non-metabolic neuronal role, broadening the gene's functional scope to synaptic gene regulation.

    Evidence FoxO6 knockout mice tested in contextual fear conditioning and novel object recognition; dendritic spine analysis; genome-wide transcriptomics

    PMID:23222102

    Open questions at the time
    • Specific synaptic target genes directly bound by FOXO6 not yet identified
    • Whether memory defects are developmental or adult-onset not fully distinguished
  5. 2014 High

    Identification of MTP as a direct FOXO6 transcriptional target connected FOXO6 to hepatic VLDL-triglyceride secretion, extending its metabolic role beyond gluconeogenesis to lipoprotein metabolism.

    Evidence ChIP, promoter mutagenesis, transgenic/knockdown mice, VLDL-TG secretion assays in HepG2 cells and human primary hepatocytes

    PMID:24437489

    Open questions at the time
    • Whether FOXO6 regulates other lipoprotein assembly genes not tested
    • Contribution relative to FoxO1 on MTP promoter not resolved
  6. 2015 High

    FOXO6 knockout mice showed protection against diet-induced glucose intolerance and reduced hepatic/adipose macrophage infiltration, establishing FOXO6 as a link between insulin resistance and tissue inflammation.

    Evidence FoxO6-KO mice on high-fat diet, glucose tolerance tests, macrophage infiltration analysis, CCR2 expression measurement

    PMID:25944898

    Open questions at the time
    • Direct transcriptional regulation of CCR2 by FOXO6 not confirmed by ChIP
    • Cell-autonomous versus systemic inflammatory effects not fully dissected
  7. 2016 High

    Identification of Plxna4 as a direct FOXO6 target gene resolved the molecular basis of FOXO6-dependent neuronal migration: FOXO6 binds DAF-16-binding elements in the Plxna4 promoter and ectopic Plxna4 rescues migration defects.

    Evidence FoxO6-KO mice, ChIP for Plxna4 promoter, genome-wide transcriptomics, genetic rescue with ectopic Plxna4

    PMID:27791111

    Open questions at the time
    • Whether Plxna4 also mediates the synaptic/memory phenotype not tested
    • Other FOXO6 neuronal targets identified by transcriptomics await individual validation
  8. 2018 High

    Demonstrating that FOXO6 activates Lats1 to engage Hippo-Yap signaling placed FOXO6 within a developmental growth-control circuit governing craniofacial morphogenesis, with PITX2 acting upstream.

    Evidence FoxO6-KO mice with craniofacial morphometry and MRI, Lats1 promoter reporter assays, Hippo reporter assays, cell proliferation analysis

    PMID:30286078

    Open questions at the time
    • Whether FOXO6-Hippo axis operates in other tissues not explored
    • Direct ChIP of FOXO6 on Lats1 promoter not shown
  9. 2020 Medium

    Multiple studies converged on FOXO6 as a hepatic lipogenic driver: physical interaction with CHOP promotes PPARγ expression during ER stress, and FOXO6 directly interacts with PPARγ and PPARα to promote lipogenesis and suppress β-oxidation, respectively.

    Evidence Co-immunoprecipitation of FOXO6–CHOP and FOXO6–PPARγ/PPARα complexes; FoxO6 transgenic/KO mice; palmitate-treated HepG2 cells

    PMID:32639626 PMID:39198274 PMID:39263959

    Open questions at the time
    • Structural basis of FOXO6–CHOP and FOXO6–PPAR interactions unknown
    • Whether these interactions are direct or bridged by co-factors not resolved
  10. 2024 Medium

    FOXO6 was shown to drive hepatic steatosis through transcriptional activation of ApoC3 and TXNIP, linking FOXO6 to NLRP3 inflammasome activation and lipid accumulation via distinct downstream effectors.

    Evidence FoxO6-Tg and KO mice, HepG2 cells, TXNIP overexpression/knockdown, inflammasome component analysis, ApoC3 gene expression in HFD and aged models

    PMID:38417829 PMID:38441531

    Open questions at the time
    • Direct ChIP of FOXO6 on ApoC3 promoter not yet published
    • Relative contribution of TXNIP versus other FOXO6 targets to inflammasome activation unclear
  11. 2025 Medium

    The METTL3/m6A–FOXO6–TXNIP axis was defined in granulosa cells, revealing post-transcriptional regulation of FOXO6 mRNA stability and establishing FOXO6–TXNIP as a conserved transcriptional module across liver and ovary.

    Evidence MeRIP-qPCR for m6A on FOXO6 mRNA, actinomycin D mRNA stability assay, luciferase reporter for TXNIP promoter, siRNA rescue in granulosa cells

    PMID:41091548

    Open questions at the time
    • Whether m6A-mediated FOXO6 stabilization operates in hepatocytes not tested
    • YTHDF reader identity for FOXO6 mRNA not identified
  12. 2026 High

    Multi-omics integration established FOXO6 as the transcriptional mediator of WNT10B-driven metabolic reprogramming in renal tubular cells, directly modulating PPARA and PKM to shift metabolism from fatty acid oxidation to glycolysis and regulate tubular senescence.

    Evidence Wnt10b KO and transgenic CKD mouse models, ChIP-seq, bulk and single-nucleus RNA-seq, ChIP-qPCR for PPARA and PKM promoters

    PMID:41963348

    Open questions at the time
    • Whether FOXO6-mediated metabolic reprogramming operates in non-renal epithelia not tested
    • Upstream mechanism linking WNT10B to FOXO6 activation not fully resolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • Structural characterization of FOXO6 (especially phosphorylated forkhead domain), genome-wide direct target identification across tissues by ChIP-seq, and the relative non-redundant contribution of FOXO6 versus other FoxO members in hepatic and neural contexts remain unresolved.
  • No crystal or cryo-EM structure of FOXO6
  • Comprehensive ChIP-seq across metabolic tissues not performed
  • Functional redundancy with FoxO1/FoxO3 not systematically tested

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 10 GO:0003677 DNA binding 7
Localization
GO:0005634 nucleus 3
Pathway
R-HSA-74160 Gene expression (Transcription) 8 R-HSA-1430728 Metabolism 6 R-HSA-162582 Signal Transduction 4 R-HSA-1266738 Developmental Biology 2
Partners
AKT1CHOPHNF4AMETTL3PPARAPPARG

Evidence

Reading pass · 31 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2003 FoxO6 is a novel FoxO transcription factor that, unlike FoxO1/3/4, remains predominantly nuclear after growth factor stimulation due to lack of a conserved C-terminal PKB phosphorylation motif; PI3K/PKB signaling mediates its nuclear export, and a chimeric approach restoring the missing region fully restores shuttling between nucleus and cytosol. GFP-fusion transfection, chimeric protein analysis, PI3K/PKB pathway inhibition/stimulation, subcellular localization imaging The Journal of biological chemistry High 12857750
2005 FoxO6 transcriptional activity is regulated by PI3K/PKB signaling via two phosphorylation sites, Thr26 (N-terminal PKB motif, acts as growth factor sensor) and Ser184 (forkhead domain PKB site, regulates DNA-binding), independent of nucleo-cytoplasmic shuttling; FoxO6 lacks the C-terminal PKB motif responsible for shuttling impairment and is not constitutively active. Site-directed mutagenesis of Thr26 and Ser184, transcriptional reporter assays, DNA-binding assays, growth factor stimulation in transfected cells The Biochemical journal High 15987244
2011 FoxO6 integrates insulin signaling with hepatic gluconeogenesis; insulin inhibits FoxO6 activity by inducing its phosphorylation and disabling its transcriptional activity without altering its subcellular distribution, a mechanism distinct from other FoxO members; elevated FoxO6 activity augments gluconeogenesis and raises fasting blood glucose, while hepatic FoxO6 depletion suppresses gluconeogenesis. Gain- and loss-of-function transgenic/KO mice, adenoviral FoxO6 overexpression in liver, primary hepatocyte glucose production assays, insulin stimulation phosphorylation assays Diabetes High 21940782
2012 FoxO6 activity in the adult hippocampus is required for memory consolidation (contextual fear conditioning, novel object recognition); FoxO6 deficiency results in decreased dendritic spine density in hippocampal neurons in vitro and in vivo, and genome-wide approaches showed FoxO6 regulates synaptic function genes upon learning. FoxO6 knockout mice, stereotactic viral injection into hippocampus, contextual fear conditioning, novel object recognition, dendritic spine density analysis, genome-wide transcriptomics Genes & development High 23222102
2013 FOXO6 physically interacts with transcription factor HNF4 in gastric cancer cells and induces C-myc expression by associating with HNF4, mediating histone acetylation and dissociation of HDAC3 from the C-myc promoter. Co-immunoprecipitation, chromatin immunoprecipitation (ChIP), overexpression/knockdown experiments, reporter assays FEBS letters Medium 23714368
2013 FoxO6 and PGC-1α form a regulatory loop in myogenic cells: PGC-1α enhances FoxO6 promoter activity and expression, while FoxO6 represses PGC-1α expression via direct binding to an upstream A/T-rich element (AAGATATCAAAACA, −2228 to −2215) in the PGC-1α promoter. Promoter reporter assays, ChIP assay, overexpression/knockdown in myogenic cells, exercise model in mice Bioscience reports Medium 23639108
2014 FoxO6 stimulates hepatic VLDL-TG production by directly binding to the MTP promoter and stimulating MTP (microsomal triglyceride transfer protein) expression; insulin inhibits this by promoting FoxO6 phosphorylation and disabling its DNA-binding activity; mutations of the FoxO6 target site in the MTP promoter abolish this induction. Chromatin immunoprecipitation, promoter reporter assays with target-site mutagenesis, transgenic mice, HepG2 cells and human primary hepatocytes, VLDL-TG secretion assays Endocrinology High 24437489
2015 FoxO6 depletion in knockout mice attenuates hepatic gluconeogenesis, lowers fasting glycemia, and reduces macrophage infiltration into liver and adipose tissues by diminishing CCR2 expression, protecting against diet-induced glucose intolerance. FoxO6 knockout mice, high-fat diet feeding, glucose tolerance tests, primary hepatocyte glucose production assays, macrophage infiltration analysis The Journal of biological chemistry High 25944898
2015 Erlotinib treatment of EGFR-mutant lung cancer cells relieves EGFR-dependent suppression of FOXO6, which then induces SOX2 expression; SOX2 in turn represses pro-apoptotic BH3-only genes BIM and BMF, constituting a survival feedback loop attenuating oncogene-addiction cell death. Knockdown and ectopic expression of SOX2 and FOXO6, erlotinib treatment, apoptosis assays, in vitro and in vivo drug resistance models eLife Medium 25686219
2015 FoxO6 promotes cell cycle arrest and inhibits proliferation in lung cancer cells by inducing USP7 expression, which elevates p53 protein levels. Overexpression and knockdown of FOXO6, western blot for USP7 and p53, cell proliferation assays Molecular medicine reports Low 25695151
2016 FoxO6 binds to DAF-16-binding elements in the Plexin A4 (Plxna4) promoter region, activates Plxna4 expression, and is required for correct radial neuronal migration in the developing neocortex; ectopic Plxna4 expression rescues migration defects in FoxO6-deficient models. FoxO6+/- and FoxO6-/- mice, siRNA knockdown, ChIP for FoxO6 binding to Plxna4 promoter, genome-wide transcriptomics, rescue by ectopic Plxna4 expression Proceedings of the National Academy of Sciences of the United States of America High 27791111
2018 FoxO6 activates Lats1 expression, thereby increasing Yap phosphorylation and activating Hippo signaling to control craniofacial growth; FoxO6-/- mice show reduced Lats1, decreased Hippo signaling, and expanded facial/skull growth; PITX2 activates FoxO6 expression upstream. FoxO6 knockout mice, in vitro reporter assays, in vivo cell proliferation analysis, craniofacial morphometry, MRI, in vitro Lats1 promoter and Hippo reporter assays PLoS genetics High 30286078
2018 FOXO6 transcriptionally regulates Sirt6 expression in breast cancer cells, as shown by ChIP and luciferase reporter assays; FOXO6 suppresses EMT and acts as a tumor suppressor partly through this regulation. ChIP-qPCR, luciferase reporter assay, siRNA knockdown, invasion and migration assays Cancer management and research Medium 30464613
2019 FoxO6 directly binds to and elevates IL-1β expression in hepatocytes; IL-1β in turn elevates PAR2 protein levels, decreasing hepatic insulin signaling (TF/PAR2 pathway); FoxO6-KO mice show reduced PAR2 signaling and decreased inflammatory cytokine expression. Virus-mediated FoxO6 activation/KO mice, siRNA knockdown in hepatocytes, IL-1β treatment, PAR2-siRNA, ChIP/binding assays implied by direct binding statement Redox biology Medium 30974318
2019 5-HT1D stabilizes PIK3R1 by inhibiting its ubiquitin-mediated degradation; the 5-HT1D/PIK3R1 interaction enhances FoxO6 expression through PI3K/Akt signaling; FoxO6 can also be directly transcriptionally activated by 5-HT1D in an Akt-independent manner. Co-IP for PIK3R1 interaction, ubiquitination assay, overexpression/knockdown, PI3K/Akt pathway inhibition, luciferase reporter assays Hepatology (Baltimore, Md.) Medium 30561038
2020 FoxO6 transcription factor interacts with C/EBP homologous protein (CHOP), an ER stress-inducible transcription factor; this physical interaction between CHOP and FoxO6 drives PPARγ expression and promotes hepatic lipid accumulation during ER stress. Co-immunoprecipitation (FoxO6–CHOP interaction), constitutively active FoxO6 transgenic and FoxO6-KO mice, palmitate treatment of HepG2 cells, lipid staining Liver international Medium 32639626
2020 FOXO6 interacts with METTL3 to trigger transcription of GPR161, which subsequently regulates β-defensin expression in response to ETEC K88 infection; m6A methylation via METTL3 controls GPR161-dependent defensin induction. MeRIP-seq, Co-IP (FOXO6–METTL3 interaction), METTL3 rescue experiments, GPR161 reporter analysis RNA biology Medium 32914682
2020 FoxO6 activates antioxidant gene expression (MnSOD, catalase) and its knockdown markedly increases melanin content in melanocytes; FoxO6 phosphorylation by Akt is essential for this activity; adenoviral FoxO6 activation reduces melanogenesis in UVB-exposed cells by decreasing oxidative stress. siRNA knockdown, adenoviral overexpression, B16F10 cells, UVB exposure model, ROS/melanin measurements, PI3K/AKT inhibition Redox biology Medium 32863230
2020 FoxO6 overexpression promotes preadipocyte cell-cycle arrest (G1 phase) and apoptosis; FoxO6 directly targets and induces expression of CCNG2 (cyclin G2) as confirmed by ChIP assay; FoxO6 also suppresses early adipogenic regulators PPARγ and C/EBPα. ChIP assay for CCNG2 promoter binding, overexpression/knockdown in preadipocytes, cell cycle analysis, Oil-Red-O staining Life sciences Medium 33290791
2020 FOXO6 directly interacts with the USP7 gene promoter and enhances its transcriptional activity, suppressing cancer cell apoptosis; USP7 in turn enhances ubiquitination of JMJD3, leading to JMJD3-mediated transcriptional activation of CLU via H3K27me3 demethylation. ChIP-qPCR, luciferase reporter assay, immunoprecipitation, ubiquitination assays, in vivo xenograft with USP7/JMJD3 inhibitors Molecular therapy oncolytics Medium 33768140
2021 FoxO6 phosphorylation by LPS leads to NF-κB activation via Akt and Pak1 pathways in the liver; LPS-induced FoxO6 phosphorylation and inactivation are Pak1-dependent in nuclear fractions, and Pak1 activation by LPS occurs in a PI3K-independent manner; Pak1 phosphorylation permits interaction between FoxO6 and Akt. Transfection with FoxO6-wt virus and FoxO6-siRNA in HepG2 cells, Pak1 pathway inhibition, nuclear fractionation, aged rat liver model Oncotarget Medium 26506521
2021 FoxO6 directly binds to the RAD51 promoter and activates its expression, promoting DNA damage repair in nucleus pulposus cells; FoxO6 upregulation reduces γH2AX foci formation, indicating reduced DNA damage. ChIP assay, luciferase reporter assay, FoxO6 overexpression, γH2AX immunofluorescence, flow cytometry European review for medical and pharmacological sciences Medium 34533813
2021 PAR2 Akt-mediated phosphorylation of FoxO6 at Ser184 suppresses FoxO6 activity and contributes to ROS-mediated inflammation during skin photoaging; PAR2 knockdown suppresses Akt/NF-κB and increases FoxO6, while PAR2 overexpression decreases FoxO6. PAR2 KO mice, PAR2 antagonist (GB83), si-PAR2 knockdown and PAR2 overexpression in UVB-irradiated HaCaT cells, UVB-irradiated hairless mice, phospho-FoxO6 (Ser184) detection Redox biology High 34082382
2023 FoxO6 promotes pathological cardiac hypertrophy and dysfunction downstream of angiotensin-II by transcriptionally activating Kif15; Kif15 in turn elevates TGF-β1 secretion from cardiomyocytes, promoting fibroblast proliferation and differentiation. FoxO6 KO and overexpressing mice, Ang-II infusion model, Kif15 inhibition, in vitro cardiomyocyte/fibroblast co-culture experiments, cardiac function measurements MedComm Medium 37799807
2023 FOXO6 transcriptionally inhibits CTRP3 expression by binding to the CTRP3 promoter (JASPAR-predicted binding, validated by ChIP and luciferase reporter assay); FOXO6-mediated CTRP3 suppression promotes OGD/R-triggered cardiac microvascular endothelial barrier disruption via SIRT1/Nrf2 signaling. ChIP, luciferase reporter assay, co-transfection of CTRP3 and FOXO6 overexpression plasmids, OGD/R model, permeability assays Folia morphologica Medium 36688407
2024 FoxO6 induces TXNIP expression in the liver; TXNIP acts as a key regulator upstream of the NLRP3 inflammasome, and FoxO6-driven TXNIP upregulation activates the NLRP3 inflammasome complex (including ASC and pro-caspase-1), leading to IL-1β production and lipid accumulation. Constitutively active FoxO6 transgenic and FoxO6-null mice, palmitate-treated HepG2 cells, inflammasome component western blot, TXNIP overexpression/knockdown Endocrinology and metabolism (Seoul, Korea) Medium 38417829
2024 FoxO6 transcriptionally activates ApoC3 expression in the liver, driving lipid accumulation, hepatic steatosis, hyperlipidemia, and hyperglycemia; high glucose upregulates FoxO6, which upregulates ApoC3 and gluconeogenic genes; FoxO6-KO mice show attenuated hepatic lipid accumulation. FoxO6 transgenic (FoxO6-Tg) and KO mice, aged rat HFD model, liver cell cultures, ApoC3 promoter and gene expression analysis Aging Medium 38441531
2024 FoxO6 physically interacts with PPARγ, and this interaction promotes hepatic lipid accumulation; betaine inhibits the FoxO6–PPARγ interaction and suppresses lipogenic gene transcription. In a separate study, FoxO6 also interacts with PPARα to suppress β-oxidation, promoting hepatic steatosis. Co-immunoprecipitation (FoxO6–PPARγ and FoxO6–PPARα interactions), FoxO6 transgenic/KO mice, db/db mice with betaine treatment, HepG2 cells with high glucose and FoxO6 overexpression Journal of medicinal food; Journal of molecular medicine (Berlin, Germany) Medium 39198274 39263959
2024 FOXG1 upregulation in neural stem cells increases FoxO6 expression; FoxO6-null NSCs cannot efficiently exit quiescence following FOXG1 elevation; Pak1 expression is upregulated by FOXG1 and downregulated upon FOXO6 loss, suggesting FOXO6 acts downstream of FOXG1 to control quiescence exit partly via Pak1-regulated macropinocytosis. Foxo6 genetic knockout in NSCs, FOXG1 overexpression, cell cycle analysis, quiescence entry/exit assays, vacuole formation analysis, Pak1 expression measurement Disease models & mechanisms Medium 39499086
2025 METTL3-mediated m6A modification stabilizes FOXO6 mRNA; FOXO6 transcriptionally activates TXNIP by directly binding to its promoter, promoting mitochondrial dysfunction and apoptosis in granulosa cells; TXNIP knockdown reverses effects of FOXO6 overexpression, confirming the METTL3/FOXO6/TXNIP axis in PCOS pathology. mRNA sequencing, MeRIP-qPCR for m6A on FOXO6 mRNA, actinomycin D mRNA stability assay, luciferase reporter assay for TXNIP promoter, siRNA knockdown and overexpression, flow cytometry for apoptosis FASEB journal Medium 41091548
2026 WNT10B signals through FOXO6 to mediate metabolic reprogramming from fatty acid oxidation to glycolysis in renal tubular cells; FOXO6 transcriptionally modulates PPARA and PKM to control this metabolic reprogramming and regulate tubular senescence fate transition; ChIP-seq, bulk and single-nucleus RNA-seq confirm FOXO6 as the transcriptional mediator of the WNT10B signal. Wnt10b KO and transgenic CKD mouse models, ChIP-seq, bulk RNA-seq, single-nucleus RNA-seq, ChIP-qPCR for PPARA and PKM promoters, FOXO6 overexpression/knockdown Nature communications High 41963348

Source papers

Stage 0 corpus · 60 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2003 FoxO6, a novel member of the FoxO class of transcription factors with distinct shuttling dynamics. The Journal of biological chemistry 275 12857750
2021 Protease-activated receptor 2 induces ROS-mediated inflammation through Akt-mediated NF-κB and FoxO6 modulation during skin photoaging. Redox biology 158 34082382
2012 FoxO6 regulates memory consolidation and synaptic function. Genes & development 111 23222102
2011 FoxO6 integrates insulin signaling with gluconeogenesis in the liver. Diabetes 103 21940782
2005 FoxO6 transcriptional activity is regulated by Thr26 and Ser184, independent of nucleo-cytoplasmic shuttling. The Biochemical journal 85 15987244
2015 Forkhead Box O6 (FoxO6) Depletion Attenuates Hepatic Gluconeogenesis and Protects against Fat-induced Glucose Disorder in Mice. The Journal of biological chemistry 48 25944898
2019 5-Hydroxytryptamine Receptor 1D Aggravates Hepatocellular Carcinoma Progression Through FoxO6 in AKT-Dependent and Independent Manners. Hepatology (Baltimore, Md.) 47 30561038
2019 FoxO6-mediated IL-1β induces hepatic insulin resistance and age-related inflammation via the TF/PAR2 pathway in aging and diabetic mice. Redox biology 44 30974318
2015 Inhibition of mutant EGFR in lung cancer cells triggers SOX2-FOXO6-dependent survival pathways. eLife 39 25686219
2013 FOXO6 promotes gastric cancer cell tumorigenicity via upregulation of C-myc. FEBS letters 34 23714368
2014 FoxO6 integrates insulin signaling with MTP for regulating VLDL production in the liver. Endocrinology 33 24437489
2018 Silencing of FOXO6 inhibits the proliferation, invasion, and glycolysis in colorectal cancer cells. Journal of cellular biochemistry 32 30321450
2020 Enterotoxigenic Escherichia coli infection promotes enteric defensin expression via FOXO6-METTL3-m6A-GPR161 signalling axis. RNA biology 31 32914682
2020 FoxO6 inhibits melanogenesis partly by elevating intracellular antioxidant capacity. Redox biology 29 32863230
2013 FoxO6 and PGC-1α form a regulatory loop in myogenic cells. Bioscience reports 29 23639108
2018 FoxO6 regulates Hippo signaling and growth of the craniofacial complex. PLoS genetics 28 30286078
2011 Candidate gene study of FOXO1, FOXO4, and FOXO6 reveals no association with human longevity in Germans. Aging cell 28 21388494
2011 Central FoxO3a and FoxO6 expression is down-regulated in obesity induced diabetes but not in aging. Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association 28 22187289
2018 Downregulation of FOXO6 in breast cancer promotes epithelial-mesenchymal transition and facilitates migration and proliferation of cancer cells. Cancer management and research 24 30464613
2015 FoxO6 inhibits cell proliferation in lung carcinoma through up-regulation of USP7. Molecular medicine reports 24 25695151
2013 FoxO6 in glucose metabolism (FoxO6). Journal of diabetes 23 23324123
2020 Knockdown of FOXO6 Inhibits Glycolysis and Reduces Cell Resistance to Paclitaxel in HCC Cells via PI3K/Akt Signaling Pathway. OncoTargets and therapy 20 32110051
2014 The essential role of FoxO6 phosphorylation in aging and calorie restriction. Age (Dordrecht, Netherlands) 20 25007762
2016 FoxO6 affects Plxna4-mediated neuronal migration during mouse cortical development. Proceedings of the National Academy of Sciences of the United States of America 17 27791111
2020 Downregulation of FOXO6 alleviates hypoxia-induced apoptosis and oxidative stress in cardiomyocytes by enhancing Nrf2 activation via upregulation of SIRT6. Journal of bioenergetics and biomembranes 16 33123950
2021 LncRNA HOXC-AS1 promotes nasopharyngeal carcinoma (NPC) progression by sponging miR-4651 and subsequently upregulating FOXO6. Journal of pharmacological sciences 15 34507637
2020 Upregulation of deubiquitinase USP7 by transcription factor FOXO6 promotes EC progression via targeting the JMJD3/CLU axis. Molecular therapy oncolytics 15 33768140
2018 Knockdown of FOXO6 inhibits high glucose-induced oxidative stress and apoptosis in retinal pigment epithelial cells. Journal of cellular biochemistry 15 30548643
2015 Suppression of FoxO6 by lipopolysaccharide in aged rat liver. Oncotarget 15 26506521
2021 Role and mechanism underlying FoxO6 in skeletal muscle in vitro and in vivo. International journal of molecular medicine 14 34080654
2023 Metformin alleviates the cognitive impairment induced by benzo[a]pyrene via glucolipid metabolism regulated by FTO/FoxO6 pathway in mice. Environmental science and pollution research international 13 37133670
2022 Biphenotypic Sinonasal Sarcoma with a Novel PAX3::FOXO6 Fusion: A Case Report and Review of the Literature. Head and neck pathology 13 36169791
2017 Involvement of the FOXO6 transcriptional factor in breast carcinogenesis. Oncotarget 13 29484124
2020 Interaction between CHOP and FoxO6 promotes hepatic lipid accumulation. Liver international : official journal of the International Association for the Study of the Liver 12 32639626
2020 Control of preadipocyte proliferation, apoptosis and early adipogenesis by the forkhead transcription factor FoxO6. Life sciences 12 33290791
2021 Knockdown of long non-coding MIR210HG inhibits cell proliferation, migration, and invasion in hepatoblastoma via the microRNA-608-FOXO6 axis. The Journal of international medical research 9 34918962
2023 Forkhead box O6 (FoxO6) promotes cardiac pathological remodeling and dysfunction by activating Kif15-TGF-β1 under aggravated afterload. MedComm 7 37799807
2021 Association of genetic variants of FBXO32 and FOXO6 in the FOXO pathway with breast cancer risk. Molecular carcinogenesis 7 34197655
2024 FoxO6-Mediated TXNIP Induces Lipid Accumulation in the Liver through NLRP3 Inflammasome Activation. Endocrinology and metabolism (Seoul, Korea) 6 38417829
2021 Upregulation of FoxO6 in nucleus pulposus cells promotes DNA damage repair via activation of RAD51. European review for medical and pharmacological sciences 6 34533813
2024 FoxO6-mediated ApoC3 upregulation promotes hepatic steatosis and hyperlipidemia in aged rats fed a high-fat diet. Aging 5 38441531
2024 Betaine Suppresses Lipid Accumulation in Liver: Inhibition of FoxO6 and PPARγ Interaction. Journal of medicinal food 5 39263959
2023 Overexpression of FTO inhibits excessive proliferation and promotes the apoptosis of human glomerular mesangial cells by alleviating FOXO6 m6A modification via YTHDF3-dependent mechanisms. Frontiers in pharmacology 5 37822879
2019 Knockdown of FOXO6 inhibits cell proliferation and ECM accumulation in glomerular mesangial cells cultured under high glucose condition. RSC advances 5 35518006
2017 Bipolar disorder risk gene FOXO6 modulates negative symptoms in schizophrenia: a neuroimaging genetics study. Journal of psychiatry & neuroscience : JPN 5 28234206
2025 FOXO6: A unique transcription factor in disease regulation and therapeutic potential. Pharmacological research 4 40058512
2024 Bifidobacterium lactis-Derived Vesicles Attenuate Hippocampal Neuroinflammation by Targeting IL-33 to Regulate FoxO6/P53 Signaling. Nutrients 4 39519420
2023 FOXO6 transcription inhibition of CTRP3 promotes OGD/R-triggered cardiac microvascular endothelial barrier disruption via SIRT1/Nrf2 signalling. Folia morphologica 4 36688407
2023 Homology Modeling, Screening, and Identification of Potential FOXO6 Inhibitors Curtail Gastric Cancer Progression: an In Silico Drug Repurposing Approach. Applied biochemistry and biotechnology 4 37086375
2024 Modelling quiescence exit of neural stem cells reveals a FOXG1-FOXO6 axis. Disease models & mechanisms 3 39499086
2024 Disulfiram/Cu targeting FOXO6 modulates sensitivity of hepatocellular carcinoma to lenvatinib via disrupt choline metabolic. Cellular signalling 3 39694126
2019 Isoflurane preconditioning protects hepatocytes from oxygen glucose deprivation injury by regulating FoxO6. Journal of biosciences 3 31894125
2024 Endoplasmic reticulum stress induces hepatic steatosis through interaction between PPARα and FoxO6 in vivo and in vitro. Journal of molecular medicine (Berlin, Germany) 1 39198274
2020 [Effects of FoxO6 on proliferation and invasion of colorectal cancer cells]. Zhonghua zhong liu za zhi [Chinese journal of oncology] 1 32482025
2026 FOXO6 activation promotes hepatic steatosis via PPARα inhibition in aged male rats. BMB reports 0 41655988
2026 Amentoflavone mitigates UVB-induced epidermal photoaging by antagonizing PAR2-driven PI3K/Akt/FoxO6 oxidative-stress signaling. Free radical biology & medicine 0 41962600
2026 Increased WNT10B/FOXO6 signaling promotes cell fate transition in renal tubular cells to aggravate renal inflammation and fibrosis. Nature communications 0 41963348
2025 Pharmaco-informatics screening of Zingiber officinale biomolecules targeting FOXO6 for chronic kidney disease therapy. Drug metabolism and personalized therapy 0 40601645
2025 FOXO6, Stabilized by METTL3-Mediated m6A Modification, Accelerates Polycystic Ovary Syndrome Progression by Transcriptional Activation of TXNIP. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 0 41091548
2025 Targeting the FoxJ3/FoxO6 axis suppresses hepatocellular carcinoma growth by inducing cell cycle arrest and apoptosis. American journal of translational research 0 41268239