Affinage

KLF9

Krueppel-like factor 9 · UniProt Q13886

Length
244 aa
Mass
27.2 kDa
Annotated
2026-06-10
100 papers in source corpus 41 papers cited in narrative 41 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

KLF9 (BTEB1) is a Krüppel-like zinc-finger transcription factor that binds GC-rich promoter elements and acts as both an activator and a repressor depending on cellular context, functioning as a hub that couples hormonal and stress signals to oxidative-stress, metabolic, differentiation, and tumor-suppressive programs (PMID:18045867, PMID:20554758, PMID:24613345). It is a direct, hormone-dependent target of multiple upstream signals: thyroid hormone receptor (PMID:18045867, PMID:28972010), glucocorticoid receptor through GRE-containing distal enhancers that loop to the KLF9 TSS (PMID:33184061, PMID:32651405, PMID:37690661), the oxidative-stress sensor Nrf2 (PMID:24613345, PMID:31569690), XBP1s under high ER stress (PMID:30282030), and BRAFV600E signaling (PMID:30664687), and its mRNA is stabilized post-transcriptionally by NAT10-mediated ac4C modification (PMID:40123006). A recurring theme is a feedforward amplification of oxidative stress: induced by Nrf2 above a ROS threshold, KLF9 represses antioxidant genes including thioredoxin reductase 2 and PRDX6, thereby raising ROS and promoting cell death (PMID:24613345, PMID:31569690, PMID:33547545). KLF9 controls mitochondrial and metabolic homeostasis by directly activating PGC-1α and regulating Mfn2 to govern mitochondrial dynamics, energy metabolism, and thermogenesis in cardiac and adipose tissue (PMID:32994275, PMID:39528719), and it drives adipogenic and hepatic lipid programs through PPARγ2/C/EBP induction and CD36 (PMID:20725087, PMID:24220850, PMID:34708234). As a context-dependent tumor suppressor it activates p53 and pro-apoptotic NOXA while repressing pro-invasive and stemness targets such as ITGA6/ITGB1, MMP28, SDF-1, ISG15, and mesenchymal/EMT genes (PMID:25242357, PMID:22144178, PMID:25288800, PMID:34968869, PMID:30913394, PMID:37010151, PMID:26210742, PMID:37400979). KLF9 also shapes differentiation and survival in neuronal, hematopoietic, and uterine systems—supporting Purkinje cell survival (PMID:23201237), promoting hematopoietic maturation downstream of TR (PMID:28972010), and acting as a progesterone-receptor co-regulator required for uterine implantation (PMID:15117941). Its activity is further tuned by direct protein-protein interactions, including synergy with C/EBPα (PMID:20725087) and JNK3 binding with phosphorylation at Ser106/Ser110 that drives axon-growth suppression (PMID:28871032).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 1999 Medium

    Established that BTEB1/KLF9 is a sequence-specific transcriptional activator, defining its core activity before its physiological roles were known.

    Evidence EMSA and reporter assays showing binding to the AP-2α autoregulatory element

    PMID:9858544

    Open questions at the time
    • No in vivo target validation
    • Mechanism of activation versus repression not resolved
  2. 2004 High

    Demonstrated that KLF9 is a physiologically required progesterone-receptor co-regulator, linking the factor to reproductive/uterine biology in vivo.

    Evidence Bteb1-null mice with uterine hypoplasia and reduced implantation gene expression

    PMID:15117941

    Open questions at the time
    • Direct PR-KLF9 binding interface not mapped
    • Downstream target promoters not defined
  3. 2007 High

    Showed that KLF9 can act through protein-protein interaction rather than direct DNA binding in autoinduction of thyroid hormone receptor, refining how it enhances transcription.

    Evidence EMSA, ChIP, and N-terminal versus zinc-finger mutants in Xenopus XTC-2 cells

    PMID:18045867

    Open questions at the time
    • Identity of the bridging partner in protein-protein mode unknown
    • Generalizability to mammalian promoters untested here
  4. 2010 High

    Placed KLF9 upstream in the adipogenic cascade and identified a direct C/EBPα cofactor interaction driving PPARγ2 induction.

    Evidence Promoter mutagenesis, Co-IP, and PPARγ2 overexpression rescue of knockdown

    PMID:20725087

    Open questions at the time
    • Structural basis of KLF9-C/EBPα interaction not defined
  5. 2010 Medium

    Revealed KLF9 as a context-switchable dual activator/repressor at a single element, explaining bidirectional control during differentiation.

    Evidence FGFR1 promoter reporter mapping and nuclear localization in myoblasts versus myotubes

    PMID:20554758

    Open questions at the time
    • What determines the activator-to-repressor switch (cofactors) unknown
  6. 2014 High

    Defined the central feedforward oxidative-stress amplifier model: Nrf2 induces KLF9, which represses antioxidant genes to raise ROS and drive cell death.

    Evidence ChIP, expression profiling, KLF9 knockout/knockdown, and in vivo bleomycin fibrosis model

    PMID:24613345

    Open questions at the time
    • Threshold sensing mechanism not molecularly defined
    • Full antioxidant target set incomplete
  7. 2014 Medium

    Identified tumor-suppressive arms of KLF9 — direct p53 activation/stabilization and genome-wide repression of stemness via ITGA6.

    Evidence ChIP, reporter, cycloheximide chase, xenografts (HCC); ChIP-seq and ITGA6 rescue (glioblastoma)

    PMID:25242357 PMID:25288800

    Open questions at the time
    • Mechanism of p53 protein stabilization unresolved
    • Context dependence of tumor suppression versus promotion unexplained
  8. 2017 High

    Connected KLF9 activity to post-translational control, showing JNK3 binding and Ser106/Ser110 phosphorylation gate its axon-growth suppression.

    Evidence Co-IP, phospho-site mutagenesis, in vitro neurite assay, and in vivo optic nerve regeneration

    PMID:28871032

    Open questions at the time
    • Effect of phosphorylation on DNA binding versus cofactor recruitment not defined
  9. 2018 High

    Extended the stress-amplifier model to the ER, showing XBP1s induces KLF9, which raises ER calcium release to worsen ER stress and death.

    Evidence ChIP, luciferase, and Klf9 knockout mouse liver tunicamycin model

    PMID:30282030

    Open questions at the time
    • Crosstalk between ER-stress and ROS arms of KLF9 not integrated
  10. 2020 High

    Mapped the glucocorticoid-induction mechanism in detail and identified KLF9 as a GR feedforward regulator controlling metabolic and inflammatory programs.

    Evidence GR ChIP-seq, GRO-seq eRNA, chromatin looping, GRE mutagenesis; zebrafish GR/klf9 CRISPR epistasis; PGC-1α direct activation in fat with transgenic/mutant mice

    PMID:32651405 PMID:32994275 PMID:33184061

    Open questions at the time
    • Tissue-specific enhancer usage not fully cataloged
    • How one factor selects activating versus repressing targets unresolved
  11. 2024 High

    Established KLF9 as a regulator of cardiac mitochondrial homeostasis through PGC-1α and Mfn2, with Mfn2 sufficient to rescue the knockout phenotype.

    Evidence Cardiac-specific Klf9 KO/transgenic mice, mitochondrial assays, and AAV-Mfn2 rescue

    PMID:39528719

    Open questions at the time
    • Direct versus indirect control of Mfn2 not fully distinguished
    • Relation to oxidative-stress arm in heart unclear
  12. 2025 High

    Added a post-transcriptional input, showing NAT10-mediated ac4C modification of KLF9 mRNA stabilizes it to promote adipogenesis.

    Evidence acRIP-seq/PCR, luciferase, NAT10 KD/OE in cells and in vivo Remodelin treatment

    PMID:40123006

    Open questions at the time
    • Whether ac4C is regulated by upstream stress/hormone signals unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • How KLF9 selects between transcriptional activation and repression at a given locus, and how its many tissue-specific target programs are coordinated by upstream signals and post-translational/post-transcriptional modifications, remains unresolved.
  • No unified cofactor logic for activator/repressor switching
  • Integration of ROS, ER-stress, metabolic, and tumor-suppressive arms into one regulatory map is incomplete

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 11 GO:0003677 DNA binding 4 GO:0060089 molecular transducer activity 3
Localization
GO:0005634 nucleus 1 GO:0005654 nucleoplasm 1
Pathway
R-HSA-74160 Gene expression (Transcription) 6 R-HSA-1266738 Developmental Biology 4 R-HSA-1430728 Metabolism 4 R-HSA-1643685 Disease 4 R-HSA-8953897 Cellular responses to stimuli 4 R-HSA-162582 Signal Transduction 3 R-HSA-168256 Immune System 3 R-HSA-5357801 Programmed Cell Death 3
Partners
CEBPAMAPK10PGR

Evidence

Reading pass · 41 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2014 Nrf2 directly stimulates KLF9 expression in response to elevated ROS above a critical threshold; KLF9 in turn binds to promoters of ROS-metabolism genes and suppresses thioredoxin reductase 2 expression, creating a feedforward loop that amplifies oxidative stress and promotes cell death. KLF9 deficiency was required for pathogenesis of bleomycin-induced pulmonary fibrosis in mice. Promoter binding (ChIP), gene expression profiling, KLF9 knockout/knockdown in cultured cells and mouse tissues, in vivo bleomycin model Molecular cell High 24613345
2010 KLF9 binds directly to two GC-box sites in the PPARγ2 proximal promoter (identified by promoter deletion/mutation analysis) and synergistically activates PPARγ2 transcription through direct protein-protein interaction with C/EBPα. PPARγ2 overexpression rescues impaired adipogenesis caused by KLF9 knockdown, placing KLF9 upstream of PPARγ2 in the adipogenic cascade. Promoter deletion/mutation analysis, Co-IP (KLF9–C/EBPα interaction), RNAi knockdown, overexpression rescue Cell death and differentiation High 20725087
2017 KLF9 interacts physically with MAPK10/JNK3 kinase; JNK3 is critical for KLF9's axon-growth-suppressive activity. Interfering with the JNK3-binding domain of KLF9, or mutating phosphorylation acceptor sites Ser106 and Ser110, abolishes KLF9-mediated neurite growth suppression in vitro and promotes optic nerve regeneration in vivo. Co-IP (KLF9–JNK3 interaction), site-directed mutagenesis (Ser106/Ser110), shRNA knockdown in vivo (optic nerve crush rat model), in vitro neurite outgrowth assay The Journal of neuroscience High 28871032
2004 KLF9/BTEB1 functionally interacts with PR-A and PR-B isoforms of the progesterone receptor in endometrial epithelial cells. Bteb1-null female mice show uterine hypoplasia, reduced implantation sites, and decreased expression of implantation genes Hoxa10 and cyclin D3, demonstrating that KLF9 is a functionally relevant PR co-regulator in uterine stroma. Bteb1 knockout mouse, uterine gene expression analysis, implantation phenotyping The Journal of biological chemistry High 15117941
2011 KLF9 is upregulated in multiple myeloma cells by bortezomib via HDAC inhibition (not ER stress). KLF9 binds the promoter of the pro-apoptotic gene NOXA, and KLF9 knockdown impairs NOXA upregulation and apoptosis induced by bortezomib or LBH589; KLF9 overexpression induces apoptosis in a partially NOXA-dependent manner. ChIP (KLF9 binding to NOXA promoter), gene expression profiling, siRNA knockdown, overexpression, HDAC inhibitor treatment Blood High 22144178
2014 KLF9 functions as a genome-wide transcriptional repressor in glioblastoma stem-like cells; it represses integrin α6 (ITGA6), and this ITGA6 repression is required for KLF9's capacity to inhibit glioblastoma cell stemness and tumorigenicity. Genome-wide ChIP-seq mapping of KLF9 targets, ITGA6 rescue experiments, sphere formation and tumor assays The Journal of biological chemistry High 25288800
2014 KLF9 directly binds GC boxes within the proximal p53 promoter to activate p53 transcription, and also increases p53 protein stability (demonstrated by cycloheximide chase), thereby suppressing hepatocellular carcinoma growth in vitro and in vivo. Promoter binding (ChIP, reporter assay), cycloheximide chase (protein stability), xenograft tumor model Cancer letters Medium 25242357
2007 BTEB1/KLF9 binds GC-rich sequences in the Xenopus TRβA gene proximal promoter in vitro and associates with the TRβA promoter in vivo in a T3- and developmental stage-dependent manner (ChIP). Induced BTEB1 expression accelerates and enhances TRβA autoinduction; this enhancement is lost with N-terminal truncation but not with zinc-finger DNA-binding mutations, indicating that BTEB1 can act through protein-protein interactions rather than direct DNA binding in this context. Electrophoretic mobility shift assay (EMSA), ChIP, BTEB1 overexpression in XTC-2 cells, N-terminal truncation and zinc-finger point mutants The Journal of biological chemistry High 18045867
2010 BTEB1/KLF9 acts as both a transcriptional activator and repressor of the FGFR1 promoter through the same Sp1-like binding element at -59 bp during myogenesis: it activates FGFR1 in proliferating myoblasts and represses it in differentiating myotubes. BTEB1 protein is nuclear-localized in both cell types. Reporter assay (FGFR1 promoter deletion/mutation), nuclear localization (immunofluorescence), overexpression in myoblasts and myotubes Molecular biology of the cell Medium 20554758
1999 BTEB-1/KLF9 binds to an autoregulatory element (A32) in the AP-2α gene promoter in a mutually exclusive manner with AP-2 and AP-2rep, and acts as a strong transcriptional activator of the AP-2α promoter in transfection assays. Electrophoretic mobility shift assay (EMSA), expression library screening, transient transfection reporter assay Molecular and cellular biology Medium 9858544
2018 XBP1s (activated by high-level ER stress) binds to an evolutionarily conserved lower-affinity site in the KLF9 promoter to activate KLF9 transcription; KLF9 in turn induces TMEM38B and ITPR1 (regulators of ER calcium storage), promoting calcium release from the ER and exacerbating ER stress and cell death. Klf9 deficiency attenuates tunicamycin-induced ER stress in mouse liver. Promoter binding (ChIP for XBP1s at KLF9 promoter), luciferase reporter assay, KLF9 knockout mouse (liver ER stress model), gene expression analysis Cell reports High 30282030
2015 KLF9 recruits to the ISG15 promoter (ChIP) and represses ISG15 expression; loss of KLF9 in Apc(Min/+) mice increases colon adenoma burden associated with upregulation of interferon-induced genes including ISG15, and ISG15 suppresses apoptosis in colorectal cancer cells. Genetic epistasis (Apc(Min/+)/Klf9 genotype comparison), ChIP (KLF9 at ISG15 promoter), siRNA knockdown in HT29 cells, microarray Carcinogenesis High 26210742
2017 KLF9 is directly regulated by thyroid hormone receptor (TR) in a TR-dependent manner in vivo and in vitro. Klf9 knockdown in zebrafish impairs hematopoietic development including erythroid maturation and T lymphopoiesis, placing KLF9 downstream of the TR-KLF9 axis in hematopoiesis. T3 treatment with TR knockdown, in vivo zebrafish klf9 morpholino knockdown, transcriptome sequencing of thymus Blood High 28972010
2020 KLF9 directly binds the Pgc1α gene promoter to stimulate its expression, promoting thermogenesis in brown and beige fat. Fat-specific Klf9 transgenic mice show increased thermogenesis and resistance to diet-induced obesity; Klf9-mutant mice show impaired thermogenic gene expression, reduced respiration, obesity, and cold sensitivity. ChIP (KLF9 binding to Pgc1α promoter), fat-specific Klf9 transgenic and mutant mice, metabolic phenotyping, Ucp1-dependent thermogenesis assay Diabetes High 32994275
2019 KLF9 directly inhibits MMP28 transcription by binding to its promoter (shown by ChIP-seq/ENCODE data and dual-luciferase assay), and forced MMP28 re-expression rescues the invasion/metastasis suppression caused by KLF9 overexpression in gastric cancer cells in vivo. ChIP-seq (ENCODE), dual-luciferase promoter assay, MMP28 rescue in vivo FASEB journal Medium 30913394
2019 BRAFV600E signaling transcriptionally upregulates KLF9; KLF9-dependent ROS are required for full-scale ERK1/2 activation and cell proliferation downstream of BRAFV600E in premalignant melanocytes. PTEN loss renders ERK1/2 activation insensitive to KLF9 and ROS. Klf9 knockout crossed with BrafCA and BrafCA/Pten-/- mouse models, N-acetylcysteine antioxidant treatment phenocopy, ERK1/2 phosphorylation analysis Oncogene High 30664687
2013 KLF9 binds the KLF-binding element at position -874 of the mouse C/EBPβ promoter (ChIP), enhances C/EBPβ expression, and drives early-phase adipogenesis in 3T3-L1 cells; siRNA knockdown of KLF9 reduces C/EBPβ expression and lipid accumulation. ChIP (KLF9 at C/EBPβ promoter), siRNA knockdown, Oil Red O staining Gene Medium 24220850
2010 KLF9 loss in mice and human endometrial stromal cells enhances BMP2 expression, while recombinant BMP2 attenuates KLF9 mRNA; KLF13 knockdown abrogates BMP2-mediated inhibition of KLF9, revealing cross-regulation among BMP2, KLF9, and KLF13 in progesterone-sensitive uterine stromal differentiation. Klf9 null mice, KLF9 siRNA in human endometrial stromal cells (HESCs), BMP2 treatment, KLF13 siRNA epistasis Endocrinology Medium 20410205
2015 In HepG2 liver cells and mouse and human primary hepatocytes, T3 induces KLF9 in a thyroid hormone receptor (TR)-dependent manner; KLF9 then regulates hundreds of target genes and cooperates with T3/TR to regulate Notch signaling pathway genes, including in human ESC and iPSC hepatocyte differentiation contexts. KLF9 knockdown (siRNA), microarray gene expression profiling, T3 + KD epistasis in HepG2 and primary hepatocytes and stem cells Stem cells Medium 25330987
2019 KLF9 directly binds to repressive KLF9 binding elements (RKBE; 5′-CA/GCCC-3′) in the Prdx6 promoter to repress Prdx6 transcription; high-dose SFN-induced Nrf2 activates KLF9 through an ARE in the KLF9 promoter, and KLF9 then suppresses PRDX6, increasing ROS and cell death. KLF9 depletion reverses this. Promoter binding analysis (RKBE elements), KLF9 knockdown (shRNA), gene expression analysis, ROS measurement Cells Medium 31569690
2020 Glucocorticoid receptor (GR) binds to four glucocorticoid response element (GRE)-containing sites near the KLF9 locus (two proximal, two distal) upon glucocorticoid treatment; these GBSs produce enhancer RNAs (eRNAs) and loop to the KLF9 TSS. CBP/p300 silencing reduces proximal GBS activity but not KLF9 expression, indicating GRE-dependent distal enhancers drive glucocorticoid induction of KLF9. ChIP-seq (GR binding), GRO-seq (eRNA), chromatin looping (3C-related), luciferase reporter with GRE mutations, CBP/p300 siRNA The Journal of biological chemistry High 33184061
2020 In zebrafish larvae, klf9 is a key glucocorticoid receptor (GR)-dependent feedforward transcriptional regulator: klf9 is underexpressed in GR-mutant larvae and strongly induced by cortisol; Klf9 loss-of-function (CRISPR) reveals that Klf9 mediates upregulation of pro-inflammatory genes in response to chronic cortisol exposure. CRISPR-Cas9 GR and klf9 mutants, RNA-seq transcriptomics, cortisol treatment Scientific reports Medium 32651405
2023 KLF9 directly binds to the TLR2 promoter in macrophages (ChIP), enhancing TLR2 expression and subsequently activating NF-κB and MAPK inflammatory signaling after myocardial infarction; KLF9 deficiency prevents adverse cardiac remodeling and suppresses inflammatory responses in this context. ChIP (KLF9 at TLR2 promoter), KLF9 knockdown in macrophages, myocardial infarction mouse model, NF-κB/MAPK signaling analysis The Korean journal of physiology & pharmacology Medium 36815257
2022 KLF9 promotes intestinal Asbt (apical sodium-dependent bile acid transporter) expression by binding to the Asbt promoter; intestine-specific Klf9 deletion reduces bile acid reabsorption, while intestinal Klf9 overexpression increases serum bile acid levels and reduces fecal bile acids. Reabsorbed bile acid regulates hepatic FGF15 and bile acid synthetic enzymes. Systemic and intestine-specific Klf9 KO mice, Klf9 intestinal transgenic mice, promoter binding assay, bile acid quantification Acta pharmacologica Sinica Medium 35105957
2024 KLF9 controls cardiac mitochondrial homeostasis: cardiac-specific Klf9 KO causes hypertrophic cardiomyopathy with mitochondrial fragmentation and impaired respiration; KLF9 regulates PGC-1α and its target genes (energy metabolism) and controls Mfn2 expression to regulate mitochondrial dynamics and mitophagy. AAV-mediated Mfn2 rescue in Klf9-CKO hearts restores cardiac function. Cardiac-specific Klf9 KO and transgenic mice, angiotensin II model, mitochondrial function assays, AAV-Mfn2 rescue Nature cardiovascular research High 39528719
2023 KLF9 directly binds the KLF9 promoter in the KLF9/CYP1A1 axis; PM2.5 stimulates KLF9 expression, and KLF9 binds the CYP1A1 promoter to drive CYP1A1 expression, activating oxidative stress and mitochondrial apoptosis pathways in trophoblasts. RNA-seq, ChIP (KLF9 at CYP1A1 promoter), KLF9 knockdown in HTR8/SVneo cells eLife Medium 37737576
2021 KLF9 represses PRDX6 expression in neuronal cells under hyperglycemic and bupivacaine conditions; KLF9 deficiency (shRNA) increases PRDX6, reduces ROS and mitochondrial dysfunction; PRDX6 knockdown abolishes the protective effect of KLF9 deficiency, placing PRDX6 downstream of KLF9-mediated oxidative stress. shRNA KLF9 knockdown, siRNA-Prdx6, ROS measurement, mitochondrial membrane potential assay, Western blot Molecular and cellular biochemistry Medium 33547545
2022 KLF9 directly binds the GSDMD promoter (luciferase reporter and ChIP) and activates GSDMD transcription; KLF9 knockout reduces GSDMD expression and attenuates LPS-induced inflammatory cytokine release and lung injury in mice. Luciferase reporter assay, ChIP, KLF9 KO mice, LPS-induced ALI model, ELISA for cytokines Autoimmunity Medium 35993279
2022 KLF9 directly binds the GRK5 promoter (ChIP) to activate GRK5 transcription; GRK5 then phosphorylates HDAC6, promoting chondrocyte ECM degradation and apoptosis in osteoarthritis. GRK5 knockdown eliminates the effects of KLF9 overexpression; HDAC6 inhibition abolishes effects of GRK5 overexpression. ChIP (KLF9 at GRK5 promoter), KLF9 KD/OE in chondrocytes, GRK5 epistasis KD, HDAC6 inhibitor (TubastatinA), OA rat model Communications biology Medium 39779910
2023 KLF9 directly binds promoter regions of mesenchymal genes in hepatocellular carcinoma cells (ChIP), repressing their expression and reversing the EMT program; KLF9 is itself directly suppressed by the mesenchymal transcription factor Slug, creating a negative feedback loop between KLF9 and EMT. ChIP (KLF9 at mesenchymal gene promoters), KLF9 OE/KD with migration/metastasis assays, Slug-KLF9 promoter repression Journal of cellular and molecular medicine Medium 37400979
2021 KLF9 overexpression in hepatocytes induces CD36 expression, increasing fatty acid uptake and triglyceride accumulation; liver-specific Klf9 knockout reduces CD36 expression and alleviates fatty liver in high-fat diet-fed mice, placing KLF9 upstream of CD36 in hepatic lipid metabolism. Adenovirus-mediated Klf9 OE/KD in primary hepatocytes, liver-specific Klf9 KO mice, CD36 mRNA/protein analysis, Oil Red O staining Sheng li xue bao / Acta physiologica Sinica Medium 34708234
2022 KLF9 binds to the SDF-1 promoter (ChIP and dual-luciferase assay) to repress SDF-1 transcription, reducing SDF-1/CXCR4 signaling and suppressing renal cell carcinoma cell proliferation, invasion, and migration. Recombinant SDF-1 rescues the inhibitory effect of KLF9 overexpression. ChIP, dual-luciferase assay, KLF9 siRNA/pcDNA overexpression, SDF-1 protein rescue The Kaohsiung journal of medical sciences Medium 37010151
2022 KLF9 binds the DDAH2 promoter and negatively regulates DDAH2 expression (luciferase reporter and ChIP); KLF9 silencing increases DDAH2 and reduces apoptosis, inflammation, and oxidative stress in high-glucose trophoblast cells; DDAH2 inhibition reverses these protective effects. Luciferase reporter assay, ChIP, KLF9 siRNA, DDAH2 siRNA epistasis, in vivo STZ-GDM mouse model Bioengineered Medium 34787071
2025 NAT10-mediated N4-acetylcytidine (ac4C) modification of KLF9 mRNA enhances KLF9 mRNA stability and translation; NAT10 overexpression promotes adipogenesis via KLF9, and NAT10 inhibition (Remodelin) reduces adipose expansion in HFD mice by suppressing KLF9 ac4C modification. KLF9 subsequently activates the CEBPA/B-PPARG pathway. acRIP-seq, RNA-seq, acRIP-PCR (KLF9 mRNA as NAT10 target), dual-luciferase reporter (NAT10 motif binding), NAT10 KD/OE in hADSCs and 3T3-L1, AAV-shRNA-NAT10 in vivo, Remodelin treatment Cell death and differentiation High 40123006
2021 In triple negative breast cancer cells, disruption of SIN3A-PF1 interaction increases KLF9 occupancy at ITGA6 and ITGB1 promoters (ChIP); KLF9 represses ITGA6 and ITGB1 expression, and KLF9 knockdown re-expresses both integrins and restores the invasive phenotype, functionally linking KLF9 to SIN3A complex-mediated repression of invasion. ChIP (KLF9 at ITGA6/ITGB1 promoters), KLF9 siRNA rescue experiment, RNA-seq Translational oncology Medium 34968869
2022 KLF9 binds directly to the KLF9 promoter (transcription factor-promoter interaction) and activates TRIM33 transcription (ChIP and dual-luciferase assay); TRIM33 overexpression suppresses TNF-α-induced proliferation, invasion and inflammation in synovial fibroblasts, and KLF9 downregulation reverses TRIM33-mediated suppression. ChIP, dual-luciferase reporter, KLF9 and TRIM33 siRNA, TNF-α-induced MH7A cell model Immunity, inflammation and disease Medium 36301038
2023 KLF9 binds to the miR-494-3p promoter and increases miR-494-3p expression (ChIP and dual-luciferase); KLF9 also binds the RGS2 promoter to promote RGS2 expression. In COPD context, KLF9-driven miR-494-3p negatively regulates PTEN, facilitating NLRP3 inflammasome activation and inflammation. ChIP (KLF9 at miR-494-3p and/or PTEN/RGS2 promoters), dual-luciferase reporter, COPD cell and mouse models Immunity, inflammation and disease Medium 37904708
2023 In cardiomyocytes, Klf9 is a direct early target of glucocorticoid receptor (GR) activation; Klf9 ChIP-seq identified 2150 Klf9-bound genes after dexamethasone treatment. Klf9 knockdown reverses GR-induced changes in 1640 genes enriched in metabolic pathways; Klf9 KD inhibits Dex-induced increases in glycolytic function and mitochondrial spare respiratory capacity. Klf9 ChIP-seq (in Dex-treated cardiomyocytes), RNA-seq with Klf9 siRNA, glycolysis stress test, mitochondrial stress test Cellular signalling High 37690661
2012 Klf9 is necessary and sufficient for Purkinje cell survival in organotypic culture in the absence of trophic factors: Klf9 overexpression increases survival from 40% to 88%; Klf9 knockdown reduces survival to 14%; Klf9 KO reduces survival by half. The absence of Klf9 can be rescued by IGF-1 and NT3 trophic factors. Lentiviral Klf9 OE/KD in organotypic cerebellar cultures, Klf9 KO mice, trophic factor rescue (IGF-1, NT3) Molecular and cellular neurosciences High 23201237
2021 miR-26a targets KLF9 in neuronal cells; KLF9 suppresses TRAF2 and KLF2 expression, facilitating neuronal damage. ASC-derived extracellular vesicle-delivered miR-26a inhibits KLF9, relieving this suppression and reducing neuronal damage in cerebral ischemia/reperfusion models in vitro and in vivo. miR-26a target validation (luciferase), miR-26a/KLF9 gain- and loss-of-function in OGD/RP cell model and mouse ischemia model, Western blot for TRAF2/KLF2 Adipocyte Medium 34311651
2025 KLF9 activates lncRNA UCA1 transcription by directly binding its promoter; UCA1 recruits EZH2 to the p27 promoter region, increasing H3K27me3 enrichment and epigenetically suppressing p27 expression, thereby exacerbating cardiomyocyte hypertrophy in HOCM. UCA1 overexpression or p27 downregulation reverses the protective effect of KLF9 knockdown. ChIP (KLF9 at UCA1 promoter; EZH2/H3K27me3 at p27 promoter), UCA1/p27 rescue experiments, ISO-induced cardiomyocyte hypertrophy model International journal of experimental pathology Medium 39909852

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2012 Common variants at CDKAL1 and KLF9 are associated with body mass index in east Asian populations. Nature genetics 208 22344221
2014 Nrf2 amplifies oxidative stress via induction of Klf9. Molecular cell 189 24613345
2012 The T3-induced gene KLF9 regulates oligodendrocyte differentiation and myelin regeneration. Molecular and cellular neurosciences 130 22472204
2010 Krüppel-like factor KLF9 regulates PPARγ transactivation at the middle stage of adipogenesis. Cell death and differentiation 111 20725087
2017 KLF9 and JNK3 Interact to Suppress Axon Regeneration in the Adult CNS. The Journal of neuroscience : the official journal of the Society for Neuroscience 85 28871032
2004 Subfertility, uterine hypoplasia, and partial progesterone resistance in mice lacking the Kruppel-like factor 9/basic transcription element-binding protein-1 (Bteb1) gene. The Journal of biological chemistry 84 15117941
2012 Endometrial miR-200c is altered during transformation into cancerous states and targets the expression of ZEBs, VEGFA, FLT1, IKKβ, KLF9, and FBLN5. Reproductive sciences (Thousand Oaks, Calif.) 81 22569286
1999 Transcriptional regulation of the AP-2alpha promoter by BTEB-1 and AP-2rep, a novel wt-1/egr-related zinc finger repressor. Molecular and cellular biology 81 9858544
2014 Kruppel-like factor-9 (KLF9) inhibits glioblastoma stemness through global transcription repression and integrin α6 inhibition. The Journal of biological chemistry 67 25288800
2014 Transcription factor KLF9 suppresses the growth of hepatocellular carcinoma cells in vivo and positively regulates p53 expression. Cancer letters 65 25242357
2008 The Krüppel-like factor 9 (KLF9) network in HEC-1-A endometrial carcinoma cells suggests the carcinogenic potential of dys-regulated KLF9 expression. Reproductive biology and endocrinology : RB&E 65 18783612
2017 Zinc chelation and Klf9 knockdown cooperatively promote axon regeneration after optic nerve injury. Experimental neurology 62 29106981
2019 KLF9-dependent ROS regulate melanoma progression in stage-specific manner. Oncogene 57 30664687
2019 KLF9 suppresses gastric cancer cell invasion and metastasis through transcriptional inhibition of MMP28. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 57 30913394
2015 Krüppel-like factor 9 (KLF9) prevents colorectal cancer through inhibition of interferon-related signaling. Carcinogenesis 55 26210742
2011 KLF9 is a novel transcriptional regulator of bortezomib- and LBH589-induced apoptosis in multiple myeloma cells. Blood 55 22144178
2018 XBP1-KLF9 Axis Acts as a Molecular Rheostat to Control the Transition from Adaptive to Cytotoxic Unfolded Protein Response. Cell reports 50 30282030
2014 KLF9, a transcription factor induced in flutamide-caused cell apoptosis, inhibits AKT activation and suppresses tumor growth of prostate cancer cells. The Prostate 48 24737412
2007 A role for basic transcription element-binding protein 1 (BTEB1) in the autoinduction of thyroid hormone receptor beta. The Journal of biological chemistry 47 18045867
2015 A thyroid hormone receptor/KLF9 axis in human hepatocytes and pluripotent stem cells. Stem cells (Dayton, Ohio) 46 25330987
2016 Activation of the Nrf2 Signaling Pathway Involving KLF9 Plays a Critical Role in Allicin Resisting Against Arsenic Trioxide-Induced Hepatotoxicity in Rats. Biological trace element research 45 27561292
2019 CircPTPRA acts as a tumor suppressor in bladder cancer by sponging miR-636 and upregulating KLF9. Aging 43 31821171
2017 Thyroid hormone regulates hematopoiesis via the TR-KLF9 axis. Blood 43 28972010
2020 Cold-Inducible Klf9 Regulates Thermogenesis of Brown and Beige Fat. Diabetes 41 32994275
2019 MicroRNA-142-3p suppresses endometriosis by regulating KLF9-mediated autophagy in vitro and in vivo. RNA biology 40 31425004
2019 Sulforaphane-Induced Klf9/Prdx6 Axis Acts as a Molecular Switch to Control Redox Signaling and Determines Fate of Cells. Cells 40 31569690
2018 Expression of KLF9 in pancreatic cancer and its effects on the invasion, migration, apoptosis, cell cycle distribution, and proliferation of pancreatic cancer cell lines. Oncology reports 40 30542730
2010 Functional differentiation of uterine stromal cells involves cross-regulation between bone morphogenetic protein 2 and Kruppel-like factor (KLF) family members KLF9 and KLF13. Endocrinology 39 20410205
2023 PM2.5 leads to adverse pregnancy outcomes by inducing trophoblast oxidative stress and mitochondrial apoptosis via KLF9/CYP1A1 transcriptional axis. eLife 36 37737576
2020 Klf9 is a key feedforward regulator of the transcriptomic response to glucocorticoid receptor activity. Scientific reports 31 32651405
2013 Activation of early phase of adipogenesis through Krüppel-like factor KLF9-mediated, enhanced expression of CCAAT/enhancer-binding protein β in 3T3-L1 cells. Gene 31 24220850
2021 Mechanism of miR-218-5p in autophagy, apoptosis and oxidative stress in rheumatoid arthritis synovial fibroblasts is mediated by KLF9 and JAK/STAT3 pathways. Journal of investigative medicine : the official publication of the American Federation for Clinical Research 30 33558275
2001 Expression of Klf9 and Klf13 in mouse development. Mechanisms of development 30 11335124
2018 Angiotensin II induces oxidative stress and upregulates neuroprotective signaling from the NRF2 and KLF9 pathway in dopaminergic cells. Free radical biology & medicine 29 30315936
2018 Combinations of Tyrosine Kinase Inhibitor and ERAD Inhibitor Promote Oxidative Stress-Induced Apoptosis through ATF4 and KLF9 in Medullary Thyroid Cancer. Molecular cancer research : MCR 29 30552230
2022 KLF9 Aggravates Streptozotocin-Induced Diabetic Cardiomyopathy by Inhibiting PPARγ/NRF2 Signalling. Cells 27 36359788
2020 The miR-140-5p/KLF9/KCNQ1 axis promotes the progression of renal cell carcinoma. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 27 32596959
2020 CircNOL10 Acts as a Sponge of miR-135a/b-5p in Suppressing Colorectal Cancer Progression via Regulating KLF9. OncoTargets and therapy 27 32606737
2020 LncRNA SNHG16 Aggravates High Glucose-Induced Podocytes Injury in Diabetic Nephropathy Through Targeting miR-106a and Thereby Up-Regulating KLF9. Diabetes, metabolic syndrome and obesity : targets and therapy 26 33116706
2020 A study of the effects of SGLT-2 inhibitors on diabetic cardiomyopathy through miR-30d/KLF9/VEGFA pathway. European review for medical and pharmacological sciences 24 32572932
2019 Krüppel-like factor KLF9 inhibits chicken intramuscular preadipocyte differentiation. British poultry science 23 31542936
2012 Klf9 is necessary and sufficient for Purkinje cell survival in organotypic culture. Molecular and cellular neurosciences 23 23201237
2002 Molecular markers of endometrial epithelial cell mitogenesis mediated by the Sp/Krüppel-like factor BTEB1. DNA and cell biology 23 11953011
2020 MiRNA-20a-5p accelerates the proliferation and invasion of non-small cell lung cancer by targeting and downregulating KLF9. European review for medical and pharmacological sciences 21 32196605
2010 Bimodal, reciprocal regulation of fibroblast growth factor receptor 1 promoter activity by BTEB1/KLF9 during myogenesis. Molecular biology of the cell 21 20554758
2022 miR-600 promotes ovarian cancer cells stemness, proliferation and metastasis via targeting KLF9. Journal of ovarian research 18 35501825
2022 Tumour-suppressing functions of the lncRNA MBNL1-AS1/miR-889-3p/KLF9 axis in human breast cancer cells. Cell cycle (Georgetown, Tex.) 17 35112997
2022 Circular RNA circ_0130438 suppresses TNF-α-induced proliferation, migration, invasion and inflammation in human fibroblast-like MH7A synoviocytes by regulating miR-130a-3p/KLF9 axis. Transplant immunology 17 35358709
2022 LncRNA TPTEP1 inhibits the migration and invasion of gastric cancer cells through miR-548d-3p/KLF9/PER1 axis. Pathology, research and practice 17 35985238
2021 microRNA-26a shuttled by extracellular vesicles secreted from adipose-derived mesenchymal stem cells reduce neuronal damage through KLF9-mediated regulation of TRAF2/KLF2 axis. Adipocyte 17 34311651
2019 MiR-141 promotes cell proliferation and invasion in non-small cell lung cancer by targeting KLF9. European review for medical and pharmacological sciences 17 31841191
2022 Hsa_circ_0037128 aggravates high glucose-induced podocytes injury in diabetic nephropathy through mediating miR-31-5p/KLF9. Autoimmunity 16 35285770
2022 Mxi1 participates in the progression of lung cancer via the microRNA-300/KLF9/GADD34 Axis. Cell death & disease 16 35501353
2021 Epigenome-Wide Association Study of Thyroid Function Traits Identifies Novel Associations of fT3 With KLF9 and DOT1L. The Journal of clinical endocrinology and metabolism 16 33484127
2021 KLF9 regulates PRDX6 expression in hyperglycemia-aggravated bupivacaine neurotoxicity. Molecular and cellular biochemistry 16 33547545
2021 KLF9 (Kruppel Like Factor 9) induced PFKFB3 (6-Phosphofructo-2-Kinase/Fructose-2, 6-Biphosphatase 3) downregulation inhibits the proliferation, metastasis and aerobic glycolysis of cutaneous squamous cell carcinoma cells. Bioengineered 16 34612136
2020 Genomic determinants implicated in the glucocorticoid-mediated induction of KLF9 in pulmonary epithelial cells. The Journal of biological chemistry 16 33184061
2019 MiR-889 promotes cell growth in human non-small cell lung cancer by regulating KLF9. Gene 16 30849540
2022 KLF9 regulates miR-338-3p/NRCAM axis to block the progression of osteosarcoma cells. Journal of Cancer 15 35399713
2022 Krüppel-like Factor 9 (KLF9) Suppresses Hepatocellular Carcinoma (HCC)-Promoting Oxidative Stress and Inflammation in Mice Fed High-Fat Diet. Cancers 15 35406507
2021 KLF9 suppresses cell growth and induces apoptosis via the AR pathway in androgen-dependent prostate cancer cells. Biochemistry and biophysics reports 15 34703906
2021 Invasive phenotype in triple negative breast cancer is inhibited by blocking SIN3A-PF1 interaction through KLF9 mediated repression of ITGA6 and ITGB1. Translational oncology 15 34968869
2022 Interference of KLF9 relieved the development of gestational diabetes mellitus by upregulating DDAH2. Bioengineered 14 34787071
2022 Down-regulation of KLF9 ameliorates LPS-caused acute lung injury and inflammation in mice via reducing GSDMD expression. Autoimmunity 14 35993279
2022 MicroRNA-494-3p facilitates the progression of bladder cancer by mediating the KLF9/RGS2 axis. The Kaohsiung journal of medical sciences 14 36098468
2021 Long non‑coding RNA DANCR represses the viability, migration and invasion of multiple myeloma cells by sponging miR‑135b‑5p to target KLF9. Molecular medicine reports 14 34278459
2015 MicroRNA-570 promotes lung carcinoma proliferation through targeting tumor suppressor KLF9. International journal of clinical and experimental pathology 14 26045791
2023 KLF9 deficiency protects the heart from inflammatory injury triggered by myocardial infarction. The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology 13 36815257
2020 MicroRNA-652 promotes cell proliferation and osteosarcoma invasion by directly targeting KLF9. Experimental and therapeutic medicine 13 32855660
2023 Krüppel-like factor 9 (KLF9) links hormone dysregulation and circadian disruption to breast cancer pathogenesis. Cancer cell international 12 36823570
2022 KLF9 positively regulates TRIM33 to inhibit abnormal synovial fibroblast proliferation, migration as well as inflammation in rheumatoid arthritis. Immunity, inflammation and disease 12 36301038
2021 LINC00664/miR-411-5p/KLF9 feedback loop contributes to the human oral squamous cell carcinoma progression. Oral diseases 12 34582069
2020 LncRNA SNHG15 promotes the proliferation of nasopharyngeal carcinoma via sponging miR-141-3p to upregulate KLF9. European review for medical and pharmacological sciences 12 32633365
2020 MiR-142-3p inhibits adipogenic differentiation and autophagy in obesity through targeting KLF9. Molecular and cellular endocrinology 12 32911017
2024 Long non-coding RNA ACTA2-AS1 suppresses metastasis of papillary thyroid cancer via regulation of miR-4428/KLF9 axis. Clinical epigenetics 11 38195623
2021 MicroRNA-200b Regulates the Proliferation and Differentiation of Ovine Preadipocytes by Targeting p27 and KLF9. Animals : an open access journal from MDPI 11 34438874
2019 Taking KLF9 to "Cort" for crimes against metabolism. The Journal of clinical investigation 11 31033481
2013 The evaluation of the FOXO1, KLF9 and YT521 genes expression in human endometrial cancer. Clinical laboratory 11 23865345
2024 Klf9 is essential for cardiac mitochondrial homeostasis. Nature cardiovascular research 10 39528719
2023 A negative feedback loop between KLF9 and the EMT program dictates metastasis of hepatocellular carcinoma. Journal of cellular and molecular medicine 10 37400979
2023 LncRNA SLC7A11-AS1 promotes the progression of hepatocellular carcinoma by mediating KLF9 ubiquitination. Neoplasma 10 37498069
2022 Exploration of the α-syn/T199678/miR-519-3p/KLF9 pathway in a PD-related α-syn pathology. Brain research bulletin 10 35654261
2020 Knockdown of KLF9 promotes the differentiation of both intramuscular and subcutaneous preadipocytes in goat. Bioscience, biotechnology, and biochemistry 10 32434447
2025 KLF9-GRK5-HDAC6 axis aggravates osteoarthritis pathogenesis by promoting chondrocyte extracellular matrix degradation and apoptosis. Communications biology 9 39779910
2025 NAT10-mediated N4-acetylcytidine modification in KLF9 mRNA promotes adipogenesis. Cell death and differentiation 9 40123006
2025 Integrative multiomics analysis reveals the subtypes and key mechanisms of platinum resistance in gastric cancer: identification of KLF9 as a promising therapeutic target. Journal of translational medicine 9 40775648
2022 Transcription factor Klf9 controls bile acid reabsorption and enterohepatic circulation in mice via promoting intestinal Asbt expression. Acta pharmacologica Sinica 9 35105957
2022 CRC Therapy Identifies Indian Hedgehog Signaling in Mouse Endometrial Epithelial Cells and Inhibition of Ihh-KLF9 as a Novel Strategy for Treating IUA. Cells 9 36552817
2023 Epigenome-Wide Association Study Reveals CpG Sites Associated with Thyroid Function and Regulatory Effects on KLF9. Thyroid : official journal of the American Thyroid Association 8 36719767
2022 Long Noncoding RNA HAND2-AS1 Suppresses Cell Proliferation, Migration, and Invasion of Bladder Cancer via miR-17-5p/KLF9 Axis. DNA and cell biology 8 35007433
2023 KLF9 inhibits the proliferation, invasion, and migration of renal cell carcinoma through the SDF-1/CXCR4 axis. The Kaohsiung journal of medical sciences 7 37010151
2023 Klf9 plays a critical role in GR -dependent metabolic adaptations in cardiomyocytes. Cellular signalling 7 37690661
2023 Mechanism of KLF9 in airway inflammation in chronic obstructive pulmonary. Immunity, inflammation and disease 7 37904708
2021 miR-483-3p, Mediated by KLF9, Functions as Tumor Suppressor in Testicular Seminoma via Targeting MMP9. Frontiers in oncology 7 33659208
2017 Lysophosphatidic acid signaling regulates the KLF9-PPARγ axis in human induced pluripotent stem cell-derived neurons. Biochemical and biophysical research communications 7 28716732
2017 Intrathecal administration of AYX2 DNA-decoy produces a long-term pain treatment in rat models of chronic pain by inhibiting the KLF6, KLF9 and KLF15 transcription factors. Molecular pain 7 28814144
2025 KLF9 aggravates the cardiomyocyte hypertrophy in hypertrophic obstructive cardiomyopathy through the lncRNA UCA1/p27 axis. International journal of experimental pathology 6 39909852
2023 Cross talk of tumor protein D52 (TPD52) with KLF9, PKCε, and MicroRNA 223 in ovarian cancer. Journal of ovarian research 6 37833790
2021 Transcriptional regulation of miR-30a by YAP impacts PTPN13 and KLF9 levels and Schwann cell proliferation. The Journal of biological chemistry 6 34265306
2021 [KLF9 regulates hepatic lipid metabolism via inducing CD36 expression]. Sheng li xue bao : [Acta physiologica Sinica] 6 34708234

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