| 2001 |
FOXQ1 (HFH-1) is mutant in satin (sa) mice, which display structurally abnormal medulla cells and defects in hair shaft differentiation. A missense mutation in the conserved winged helix DNA-binding domain causes the same phenotype as an intragenic deletion, establishing FOXQ1 as required for hair medulla differentiation. |
Genetic mapping, identification of intragenic deletion and ENU-induced missense mutation in DNA-binding domain, phenotypic characterization of homozygous mutants |
Genesis |
High |
11309849
|
| 2000 |
HFH-1 (FOXQ1) represses transcription of smooth muscle-specific promoters (telokin, SM22α) by binding to a forkhead consensus site in an AT-rich region of the telokin promoter. The DNA-binding domain alone is sufficient for repression, and HFH-1 does not disrupt serum response factor binding to adjacent CArG boxes, indicating it blocks other positive-acting factors. |
Reporter gene (promoter-luciferase) assays in A10 vascular smooth muscle cells, overexpression of HFH-1 and DNA-binding domain alone, gel-shift/footprint to map binding site |
The Journal of biological chemistry |
High |
10896677
|
| 2002 |
The DNA-binding domain of HFH-1 (FOXQ1) adopts a winged-helix fold that forms DNA complexes with different local conformations than the closely related Genesis protein when contacting the same DNA sequence, as determined by heteronuclear NMR. |
Heteronuclear NMR structure determination of HFH-1 DNA-binding domain in free and DNA-bound states; structural comparison with Genesis |
Biochemistry |
High |
11876636
|
| 2001 |
The human FOXQ1 gene encodes a 403-amino acid protein with a conserved HNF-3/forkhead DNA-binding domain (100% identity with mouse and rat) and two putative transcriptional activation domains. The gene is expressed predominantly in stomach, trachea, bladder, and salivary gland. |
Isolation and sequencing of human genomic and cDNA clones; sequence alignment; tissue expression by Northern/RT-PCR |
DNA and cell biology |
Medium |
11747606
|
| 2006 |
FOXQ1 is a direct downstream transcriptional target of HOXC13 during hair follicle medulla differentiation. HOXC13 binds the Foxq1 promoter and activates its expression, as shown by DNA binding studies, co-transfection reporter assays, and ChIP. Expression of additional medulla-specific genes depends on functional Foxq1, placing FOXQ1 downstream of HOXC13 in a hair differentiation pathway. |
ChIP assay, co-transfection/reporter assay, gene array in Hoxc13-transgenic mice, validation in satin (Foxq1-mutant) mice |
The Journal of biological chemistry |
High |
16835220
|
| 2008 |
FOXQ1 is required for gastric acid secretion in mice. Foxq1-deficient mice lack gastric acid secretion in response to secretagogue stimuli despite normal parietal cell development; ultrastructural analysis suggests impaired fusion of cytoplasmic tubulovesicles with the apical membrane of secretory canaliculi. |
Foxq1 knockout mouse model, gastric acid secretion assays with secretagogues, transmission electron microscopy, parietal cell morphology analysis |
Cytogenetic and genome research |
High |
18544931
|
| 2010 |
FOXQ1 transcriptionally activates p21(CIP1/WAF1) by binding to its promoter, as shown by reporter assay and ChIP. FOXQ1 overexpression also upregulates VEGFA, WNT3A, RSPO2, and BCL11A, mediating angiogenic and antiapoptotic effects in vivo. |
siRNA knockdown microarray analysis, luciferase reporter assay, chromatin immunoprecipitation (ChIP), stable overexpression xenograft model, CD31 and TUNEL staining |
Cancer research |
High |
20145154
|
| 2011 |
FOXQ1 promotes EMT and breast cancer metastasis by directly repressing E-cadherin (CDH1) expression through binding to the E-box in its promoter region. FOXQ1 expression is induced by TGF-β1, and FOXQ1 knockdown blocks TGF-β1-induced EMT. |
Ectopic expression and shRNA knockdown, in vitro migration/invasion assays, in vivo lung metastasis model, ChIP and promoter binding assay for E-cadherin E-box |
Cancer research |
High |
21285253 21346143
|
| 2011 |
FOXQ1 promotes EMT in breast cancer cells; RNAi suppression of FOXQ1 reverses EMT, and enforced FOXQ1 expression induces EMT in differentiated human mammary epithelial cells associated with transcriptional inactivation of E-cadherin (CDH1). |
RNAi knockdown, ectopic expression, 3D Matrigel culture, CDH1 promoter reporter assays |
Cancer research |
High |
21346143
|
| 2011 |
Repression of FoxQ1 in mammary epithelial cells increases E-cadherin expression, promotes cell-cell contacts, rearranges the actin cytoskeleton, slows G1-phase cell cycle progression, and enhances migration of coherent epithelial sheets. FoxQ1 was identified as a downstream mediator of TGF-β1-induced gene expression changes including Ets-1, Zeb1, and Zeb2. |
FoxQ1 knockdown by RNAi, cell morphology analysis, gene expression profiling, cell cycle analysis by flow cytometry, migration assays |
Journal of cellular physiology |
Medium |
20717954
|
| 2013 |
FOXQ1 directly binds the TWIST1 promoter and transcriptionally activates TWIST1 expression, thereby modulating TWIST1-dependent metastatic phenotypes in colorectal cancer cells. Enhanced FOXQ1 expression increased migration, invasion, and distant metastasis in a chicken chorioallantoic membrane model. |
ChIP assay, luciferase reporter assay, forced expression and RNA silencing, in vivo chorioallantoic membrane metastasis assay |
Molecular cancer research |
High |
23723077
|
| 2013 |
FoxQ1 directly binds the NRXN3 promoter and represses its transcriptional activity, promoting glioma cell proliferation and migration. Knockdown of FoxQ1 reduces these behaviors, while NRXN3 expression is negatively correlated with FoxQ1 in glioma tissues. |
ChIP assay, luciferase reporter assay, stable FoxQ1 knockdown and overexpression cell lines, MTT proliferation assay, transwell migration assay |
PloS one |
Medium |
23383267
|
| 2013 |
FOXQ1 is a direct transcriptional target of canonical Wnt signaling. FOXQ1 promoter contains Wnt-responsive elements, and Wnt pathway activation induces FOXQ1 expression as demonstrated by ChIP and luciferase reporter assays. |
ChIP, luciferase reporter assay, qRT-PCR and western blot in Wnt-stimulated CRC cell lines and laser microdissected human biopsies |
PloS one |
High |
23555880
|
| 2014 |
FOXQ1 directly binds the Sox12 promoter and transactivates Sox12 expression in hepatocellular carcinoma. Sox12 in turn activates Twist1 and FGFBP1 transcription to promote HCC invasion and metastasis, placing FOXQ1 upstream of the Sox12-Twist1/FGFBP1 axis. |
Serial deletion, site-directed mutagenesis, and ChIP assays on Sox12 promoter; siRNA knockdown and rescue experiments; in vivo metastasis models |
Hepatology |
High |
25704764
|
| 2014 |
Foxq1 promotes breast cancer stemness traits and chemoresistance by transcriptionally activating PDGFRα and PDGFRβ directly or indirectly through the Foxq1/Twist1 axis. Knockdown of both PDGFRα and β reverses Foxq1-promoted oncogenesis more effectively than either alone; PDGFRβ is the more potent mediator of Foxq1-promoted stemness. |
Expression profiling, siRNA knockdown, pharmacological PDGFR inhibition, in vitro stemness assays, in vivo xenograft model |
Cancer research |
Medium |
25502837
|
| 2014 |
FOXQ1 directly binds the TGF-β1 promoter (E-cadherin and N-cadherin promoter regions confirmed by ChIP) and activates TGF-β1 expression, and TGF-β1 in turn upregulates FOXQ1, forming a positive feedback loop that drives EMT. |
ChIP assay, shRNA knockdown, wound healing and invasion assays, RT-PCR |
Molecular and cellular biochemistry |
Medium |
25287361
|
| 2015 |
FOXQ1 silencing in colorectal cancer cells prevents nuclear translocation of β-catenin, thereby reducing Wnt signaling activity. Additionally, TGF-β1 induces FOXQ1 expression and promotes cancer cell migration/invasion via FOXQ1, placing FOXQ1 as a mediator of crosstalk between TGF-β and Wnt signaling pathways. |
siRNA knockdown, β-catenin nuclear fractionation and immunofluorescence, in vitro invasion/migration assays, TGF-β1 stimulation |
Cancer biology & therapy |
Medium |
25955104
|
| 2015 |
FOXQ1 transcriptionally represses CDH1 (E-cadherin) in esophageal cancer by binding to its promoter as a transcriptional repressor, promoting cell proliferation and metastasis. CDH1 silencing rescues migratory ability lost by FOXQ1 knockdown. |
Reporter gene assay, RT-PCR, western blot, overexpression and knockdown, migration chamber assay, rescue experiment |
Biomedicine & pharmacotherapy |
Medium |
26349968
|
| 2016 |
FOXQ1 directly binds the SIRT1 promoter and transcriptionally upregulates SIRT1, which in turn inhibits NF-κB-driven expression of inflammatory cytokines IL-6 and IL-8. This FOXQ1-SIRT1 axis suppresses replicative senescence in human fibroblasts. |
ChIP assay demonstrating FOXQ1 binding to SIRT1 promoter, FOXQ1 overexpression and knockdown, cytokine measurement, senescence assays |
Cell death & disease |
High |
28726780
|
| 2016 |
Hepatic FOXQ1 regulates gluconeogenesis by interacting with FOXO1 and blocking its binding to insulin response elements in gluconeogenic gene promoters. FOXQ1 rescue in diabetic mice decreases blood glucose; FOXQ1 deficiency increases blood glucose and impairs glucose tolerance. |
Primary hepatocyte overexpression/deficiency, in vivo FOXQ1 hepatic rescue in db/db and HFD-obese mice, glucose tolerance tests, co-immunoprecipitation of FOXQ1-FOXO1 interaction, promoter binding assays |
Diabetologia |
High |
27421728
|
| 2016 |
FOXQ1 promotes colorectal cancer cell migration and invasion through activation of PI3K/AKT signaling. FOXQ1 knockdown reduces phosphorylated FAK, PI3K, and AKT levels as well as MMP-2/9 expression. |
siRNA knockdown, western blot for signaling components, migration/invasion assays, in vivo xenograft |
American journal of translational research |
Low |
28559972
|
| 2016 |
FOXQ1 regulates prostate cancer cell proliferation and apoptosis by controlling BCL11A and MDM2 expression. Overexpression of BCL11A reverses the pro-apoptotic effects of FOXQ1 inhibition and restores MDM2 expression, placing BCL11A downstream of FOXQ1. |
siRNA knockdown, BCL11A overexpression rescue assay, flow cytometry apoptosis, western blot |
Oncology reports |
Medium |
27573292
|
| 2017 |
FOXQ1 directly binds the NDRG1 promoter and transactivates NDRG1 expression in HCC, which activates pSTAT6/CCL26 signaling to recruit hepatic stellate cells and create a positive feedback loop with cancer-associated fibroblasts enhancing tumor initiation. |
ChIP assay, luciferase reporter assay, Co-culture models, siRNA knockdown, in vivo HCC initiation assays |
Cancer letters |
Medium |
29248714
|
| 2017 |
FOXQ1 functions as a melanoma suppressor rather than oncogene, suppressing EMT, invasion, and metastasis in melanocyte lineage cells. This lineage-specific reversal depends on FOXQ1's ability to repress (in melanoma) rather than activate (in carcinomas) N-cadherin (CDH2) transcription. The switch is determined by the nuclear β-catenin/TLE ratio: high in carcinomas drives CDH2 activation; low in melanoma drives repression. FOXQ1 interacts with nuclear β-catenin and TLE proteins. |
Reciprocal Co-IP of FOXQ1 with β-catenin and TLE proteins, loss- and gain-of-function in melanoma and carcinoma cells, in vivo xenograft/metastasis models, manipulation of β-catenin and TLE levels to switch CDH2 regulation |
Cell reports |
High |
28930679
|
| 2017 |
FOXQ1 promotes NKTCL cell proliferation and blocks apoptosis via the Sonic Hedgehog (Shh) signaling pathway; FOXQ1 knockdown downregulates Shh pathway proteins, blocks cells in G0/G1, and increases apoptosis with elevated Bax/Caspase-3 and reduced Bcl-2. Exogenous Shh reverses the effects of FOXQ1 knockdown. |
shRNA knockdown, Shh pathway inhibitor (Cyclopamine) and recombinant Shh rescue, CCK-8, BrdU incorporation, flow cytometry, western blot |
Leukemia research |
Medium |
29132010
|
| 2017 |
IL-4 induces FoxQ1 expression in human monocytes and macrophages. FoxQ1 overexpression in RAW264.7 monocytic cells facilitates their migration towards MCP-1 and is associated with decreased expression of migration-regulating genes claudin-11 and plexin C1, and increases TNFα secretion after LPS challenge. |
IL-4 stimulation of primary monocytes and macrophages, FoxQ1 overexpression in RAW cells, migration assay, RT-PCR for target genes, TNFα ELISA |
Scientific reports |
Medium |
29203829
|
| 2018 |
FOXQ1 directly activates MITF gene transcription to induce differentiation in normal and transformed melanocytic cells. FOXQ1-mediated pigmentation depends on activation of the cAMP/CREB1 pathway, and FOXQ1 mediates BRAFV600E-dependent regulation of MITF levels. |
ChIP and promoter reporter assays for MITF, cAMP/CREB1 pathway activation experiments, BRAFV600E expression models, gain- and loss-of-function in melanocytic cells and in vivo mouse pigmentation models |
Cell death and differentiation |
High |
29463842
|
| 2018 |
EWS-FLI1 cooperates with Foxq1 in mouse Ewing sarcoma through a direct protein-protein interaction (EWS portion of EWS-FLI1 binds Foxq1). Foxq1 Fox-motif binding sites are enriched within EWS-FLI1 ChIP-seq peaks. Trib1 and Nrg1 are co-regulated target genes of EWS-FLI1/Foxq1 important for cell proliferation and survival. |
ChIP-seq for EWS-FLI1 binding, Co-immunoprecipitation of Foxq1 with EWS-FLI1, motif analysis, target gene validation |
Cancer science |
Medium |
29945296
|
| 2019 |
FOXF2 and FOXQ1 engage in mutual transcriptional repression in basal-like breast cancer. FOXF2 recruits nuclear receptor corepressor 1 (NCoR1) and HDAC3 to the FOXQ1 promoter to suppress FOXQ1 transcription, whereas FOXQ1 does not use this mechanism to repress FOXF2. |
ChIP assay demonstrating NCoR1/HDAC3 recruitment to FOXQ1 promoter by FOXF2, luciferase reporter assays, ectopic expression and knockdown experiments |
FASEB journal |
High |
30807702
|
| 2020 |
HuR (ELAVL1) RNA-binding protein directly binds FOXQ1 mRNA and stabilizes it. The HuR inhibitor KH-3 disrupts the HuR-FOXQ1 mRNA interaction, leading to inhibition of breast cancer invasion and metastasis. |
RNA immunoprecipitation (RIP) identifying HuR-FOXQ1 mRNA interaction, HuR inhibitor KH-3 treatment, in vitro invasion assays, in vivo lung metastasis model |
Communications biology |
High |
32332873
|
| 2020 |
FOXQ1 promotes osteogenic differentiation of bone mesenchymal stem cells (BMSCs) by promoting nuclear translocation of β-catenin and enhancing Wnt/β-catenin signaling. FOXQ1 physically interacts with Annexin A2 (ANXA2), and ANXA2 depletion reverses the FOXQ1-promoted Wnt/β-catenin activation. |
Lentiviral overexpression/knockdown of Foxq1, TOPFlash/FOPFlash reporter, immunofluorescence for β-catenin, Co-IP mass spectrometry identifying ANXA2 as FOXQ1-binding partner, ANXA2 siRNA rescue |
Stem cell research & therapy |
Medium |
32943107
|
| 2021 |
FOXQ1 directly regulates transcription of electron transport chain Complex I subunits NDUFS1 and NDUFV1 by binding to their promoters (ChIP). FOXQ1 overexpression increases Complex I assembly and activity, oxygen consumption, and intracellular pyruvate, lactate, and ATP levels in breast cancer cells. |
ChIP assay for FOXQ1 at NDUFS1 and NDUFV1 promoters, RNA-seq after FOXQ1 overexpression, Complex I activity and assembly assays, Seahorse oxygen consumption measurement |
Molecular carcinogenesis |
High |
34939230
|
| 2021 |
FOXQ1 directly binds the LDHA gene promoter in mouse Sertoli cells and transactivates Ldha expression, thereby regulating lactate production essential for germ cell survival. Foxq1-knockout males are subfertile with oligoasthenozoospermia due to lactate deficiency; LDHA overexpression rescues lactate production in Foxq1-deficient Sertoli cells. |
CRISPR-Cas9 Foxq1 knockout mice, ChIP assay for FOXQ1 at Ldha promoter, lentiviral LDHA overexpression rescue, lactate measurement, fertility phenotyping |
Histochemistry and cell biology |
High |
34091745
|
| 2021 |
FOXQ1 directly binds the EGFR promoter and transcriptionally activates EGFR expression in NPC cells, promoting vasculogenic mimicry (VM) formation and metastasis via the EGFR signaling pathway. EGFR inhibitors (Nimotuzumab or Erlotinib) block Foxq1-induced VM. |
Luciferase reporter gene assay, ChIP assay for Foxq1 at EGFR promoter, in vitro VM formation, in vivo metastasis model, EGFR inhibitor treatment |
Cell death & disease |
High |
33875643
|
| 2022 |
FOXQ1 initiates EMT by recruiting the MLL/KMT2 histone methyltransferase complex as a transcriptional coactivator. The Forkhead box domain of FOXQ1 directly binds the MLL core complex subunit RbBP5 without disrupting FOXQ1 DNA binding. FOXQ1 promoter recognition precedes MLL complex assembly and H3K4me3 deposition at EMT gene promoters. Disruption of the FOXQ1-RbBP5 interaction or pharmacologic targeting of KMT2/MLL inhibits EMT and in vivo tumor progression. |
Co-IP of FOXQ1 with MLL complex subunits including RbBP5, domain-mapping mutagenesis of FOXQ1-RbBP5 interaction, ChIP-seq for H3K4me3 at EMT gene promoters, pharmacologic KMT2 inhibition, in vivo tumor progression assays |
Nature communications |
High |
36319643
|
| 2022 |
FOXQ1 directly binds the SIRT1 promoter and transcriptionally activates SIRT1; SIRT1 in turn enhances β-catenin expression and nuclear translocation, augmenting Wnt signaling, stemness, and radio-resistance of CRC cells. |
Luciferase reporter assay, Co-IP, ChIP assay for FOXQ1 at SIRT1 promoter, FOXQ1/SIRT1 knockdown and overexpression, xenograft model |
Journal of experimental & clinical cancer research |
Medium |
35183223
|
| 2022 |
FOXQ1 is a differential activator of Wnt target gene expression. Upon Wnt pathway activation, FOXQ1 synergizes with the β-catenin nuclear complex to boost major Wnt targets; in parallel, FOXQ1 independently controls other Wnt target genes in a β-catenin-independent manner. FOXQ1 occupies Wnt-responsive elements in β-catenin target gene promoters and recruits a similar set of co-factors as TCF7L1. |
RNA-seq in CRC cell lines, ChIP for FOXQ1 at Wnt-responsive elements, comparison of co-factor recruitment with TCF7L1, FOXQ1 knockdown in Wnt-stimulated cells |
Journal of cell science |
High |
36124643
|
| 2022 |
FOXQ1 and SNAI1 act as independent EMT transcription factors sharing a common downstream target DDR2 (the most upregulated receptor tyrosine kinase). DDR2 is a shared effector mediating cell motility without significantly affecting EMT marker expression or stem cell population. DDR2 knockdown in FOXQ1-driven EMT models alters the global metabolic profile including glutamine-glutamate and aspartate recycling. |
Ectopic expression of FOXQ1 and SNAI1 in HMLE cells, transcriptomic analysis, DDR2 knockdown and overexpression, motility assays, metabolomics |
Cancer research communications |
Medium |
36713812
|
| 2022 |
STUB1 directs FOXQ1-mediated transactivation of Ldha in mouse Sertoli cells via K63-linked non-proteolytic polyubiquitination of FOXQ1, facilitating lactate production in FSH-stimulated Sertoli cells. Conditional Stub1 knockout in Sertoli cells impairs fertility due to lactate deficiency. |
Sertoli cell-specific Stub1 conditional knockout (Amh-Cre), ChIP assay, in vivo ubiquitination assay, luciferase reporter assay, lentiviral LDHA overexpression rescue |
Cell and tissue research |
High |
36575252
|
| 2023 |
FOXQ1 directly binds the circ_0000643 host gene promoter (ChIP assay) to increase circ_0000643 levels. circ_0000643 then sponges miR-153, which relieves repression of SLC7A11, reducing ferroptosis in breast cancer cells. |
ChIP assay for FOXQ1 at circ_0000643 host gene promoter, luciferase reporter assay, RIP assay for circ_0000643-miR-153 interaction, ferroptosis assays |
Experimental cell research |
Medium |
37591453
|
| 2023 |
FOXQ1 promotes LDHA transcription in pancreatic cancer cells to modulate aerobic glycolysis, thereby enhancing cell proliferation, tumor stemness, invasion, and metastasis. FOXQ1 silencing reduces LDHA expression and glycolysis. |
FOXQ1 overexpression and knockdown, ChIP assay for FOXQ1 at LDHA promoter, glycolysis measurement, in vivo xenograft model |
Cell death & disease |
Medium |
37875474
|
| 2023 |
KSHV immediate early protein ORF45 induces FOXQ1 expression in oral epithelial cells via the ORF45-RSK (ERK-p90RSK) signaling pathway. RTA also induces FOXQ1. FOXQ1 depletion reduces KSHV lytic protein accumulation and viral DNA, identifying FOXQ1 as a lytic cycle-sustaining host factor. FOXQ1 induction is associated with accumulation of activating histone acetylation marks at the FOXQ1 promoter. |
Transcriptome analysis of KSHV-infected HGEP cells, FOXQ1 knockdown in TIGK cells, screen of KSHV lytic proteins by ectopic expression, ORF45 RSK-activation mutant, ChIP for histone acetylation at FOXQ1 promoter |
Journal of virology |
Medium |
36815831
|
| 2023 |
FOXQ1 transcriptionally activates CREB5, which suppresses NF-κB nuclear translocation of p65 to protect against sepsis-induced acute kidney injury. USP10 deubiquitinates FOXQ1, reducing its ubiquitination and promoting protein stability, and USP10 overexpression alleviates LPS-induced cell injury through FOXQ1. |
CLP mouse model, LPS-induced HK-2 cell model, luciferase reporter for CREB5, Co-IP for USP10-FOXQ1 interaction, in vivo ubiquitination assay, phosphorylation level assessment of p65 |
Biochimica et biophysica acta. Molecular basis of disease |
Medium |
38960057
|
| 2023 |
NAC1 interacts with BCL6 via NAC1's C-terminal BEN domain, and the NAC1-BCL6 complex binds the FOXQ1 promoter to activate FOXQ1 transcription. NAC1 also attenuates BCL6 auto-downregulation in ovarian cancer. |
Co-IP of NAC1 and BCL6, ChIP of NAC1-BCL6 complex at FOXQ1 promoter, luciferase reporter assay, Cistrome database analysis |
Aging |
Medium |
32412910
|
| 2023 |
The FGFR1-MEK-ERK2 signaling pathway upregulates FOXQ1 gene expression through c-FOS binding to the FOXQ1 promoter. ERK2 (but not ERK1) is specifically required; ERK2 knockout suppresses FGFR1-stimulated FOXQ1 expression, and ectopic FOXQ1 rescues FGFR1-stimulated cell growth in ERK2-KO cells. |
MEK/ERK inhibitors, ERK1 and ERK2 CRISPR knockout, ChIP for c-FOS at FOXQ1 promoter, FOXQ1 rescue experiment, xenograft tumor growth |
International journal of biological sciences |
High |
36778115
|
| 2023 |
HNRNPA2B1 binds m6A-modified FOXQ1 mRNA and enhances its stability, increasing FOXQ1 protein expression. Silencing HNRNPA2B1 reduces FOXQ1 protein levels and suppresses OSCC malignant phenotypes. |
m6A site prediction, RIP/Co-IP for HNRNPA2B1-FOXQ1 mRNA interaction, mRNA stability assay, HNRNPA2B1 knockdown and overexpression, xenograft model |
IUBMB life |
Medium |
38265150
|
| 2023 |
FOXQ1 expression is maintained by SIRT4-mediated metabolic control via the FOXQ1-SIRT4-GDH axis. FOXQ1 maintains SIRT4 expression; SIRT4 suppresses GDH via ADP-ribosylation. During senescence, FOXQ1 and SIRT4 decrease, causing increased GDH activity that produces α-KG, leading to H3K9me3 erasure at IL-6/IL-8 promoters and driving SASP. |
GDH activity assay in aged mice and senescent fibroblasts, FOXQ1/SIRT4 expression manipulation, ChIP for H3K9me3 at IL-6/IL-8 promoters, GDH pharmacological inhibition, α-KG metabolite measurement |
Cell death & disease |
Medium |
37516739
|
| 2024 |
PARP1 stabilizes FOXQ1 protein by inhibiting its ubiquitination via the E3 ubiquitin ligase CHIP (STUB1), thereby protecting FOXQ1 from proteolytic degradation. Stabilized FOXQ1 activates LAMB3 transcription (ChIP-seq and luciferase assay), activating the WNT/β-catenin pathway to promote ovarian cancer progression. |
Co-IP of PARP1 and FOXQ1, mass spectrometry, in vivo ubiquitination assay, ChIP-seq, luciferase assay for LAMB3 promoter, PARP inhibitor experiments, xenograft and clinical samples |
Oncogene |
High |
38297082
|
| 2024 |
JNK1 directly phosphorylates FOXQ1 at serine 248 in HCC cells in response to sorafenib. Phosphorylated FOXQ1 gains high affinity for the ETHE1 promoter and activates ETHE1 transcription. ETHE1 reduces intracellular lipid peroxidation and iron levels, thereby suppressing sorafenib-induced ferroptosis. This JNK1-FOXQ1(pS248)-ETHE1 axis mediates sorafenib resistance. |
In vitro kinase assay (JNK1 phosphorylating FOXQ1-S248), site-directed mutagenesis of S248, ChIP for FOXQ1 at ETHE1 promoter, flow cytometry for lipid peroxidation/iron, functional ferroptosis assays |
Cell death & disease |
High |
38839744
|
| 2024 |
p53 is a negative transcriptional regulator of FOXQ1. p53 binds close to the FOXQ1 transcription start site and suppresses FOXQ1 expression. Pharmacological p53 activation (nutlin-3 or doxorubicin) reduces FOXQ1 mRNA and protein in cancer cells with wild-type p53; p53 mutations are associated with elevated FOXQ1 expression in human cancers. |
CRISPR-Cas9-based genomic locus proteomics to identify p53 as FOXQ1 regulator, ChIP-qPCR for p53 at FOXQ1 promoter, luciferase reporter assay, p53 gain/loss-of-function, nutlin-3 and doxorubicin pharmacological treatment |
The Journal of biological chemistry |
High |
38432629
|
| 2024 |
FOXQ1 regulates brain endothelial cell mitochondrial function through two direct mechanisms: (1) regulation of calcium signaling via huntingtin-associated protein (HAP1)-mediated ER-mitochondria calcium transfer, and (2) regulation of mitochondrial cristae integrity via ADCK1-dependent cristae organization. Endothelial-specific Foxq1 conditional knockout causes disrupted cristae morphology, reduced oxygen consumption, and impaired ATP production. |
Endothelial-specific conditional Foxq1 knockout, comparative transcriptomics, mitochondrial function assays (oxygen consumption, ATP production), electron microscopy for cristae, calcium imaging, identification of HAP1 and ADCK1 as direct targets |
Advanced science |
High |
40884816
|
| 2024 |
Foxq1 alleviates postoperative cognitive dysfunction by activating the cannabinoid receptor CB2R, with oleamide as a mediator. Foxq1 overexpression (AAV) or oleamide administration improve cognitive performance and reduce hippocampal neuroinflammation; these effects are blocked by CB2R antagonist AM630. |
AAV-mediated hippocampal Foxq1 overexpression, oleamide administration, CB2R antagonist (AM630) rescue experiment, behavioral tests, inflammatory cytokine measurement, transcriptomic/metabolomic analysis |
Brain pathology |
Medium |
39046224
|
| 2024 |
Foxq1 promotes alveolar epithelial cell death in acute lung injury through Tle1-mediated inhibition of the NF-κB/Bcl2/Bax signaling pathway. Foxq1 knockdown promotes cell survival while overexpression has the opposite effect, with Tle1 identified as a mediating partner. |
LPS-induced ALI mouse model, Foxq1 knockdown and overexpression in MLE-12 cells, western blot for NF-κB/Bcl2/Bax, Tle1 functional assays |
American journal of respiratory cell and molecular biology |
Medium |
38574238
|
| 2025 |
p300 acetylates FOXQ1 at Lys190, enabling recognition and binding by BRD4. The resulting FOXQ1-p300-BRD4-RNA Pol II complex binds super-enhancer regions of target oncogenes, and acetylation at Lys190 directly enhances FOXQ1 binding affinity to super-enhancers, driving CRC proliferation and metastasis. |
ChIP-seq for FOXQ1 and BRD4 at super-enhancers, Co-IP of FOXQ1 complex, acetylation site mapping (Lys190), site-directed mutagenesis, luciferase reporter assay, in vitro and in vivo functional assays |
Communications biology |
High |
40624346
|