Affinage

SQLE

Squalene monooxygenase · UniProt Q14534

Length
574 aa
Mass
63.9 kDa
Annotated
2026-06-10
62 papers in source corpus 25 papers cited in narrative 25 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

SQLE (squalene epoxidase) is the second rate-limiting enzyme of cholesterol biosynthesis, converting squalene to 2,3-oxidosqualene, and its activity sits at a node where transcriptional control, substrate/product signaling, and protein turnover converge to govern sterol levels, membrane biology, and tumor growth (PMID:28342963, PMID:30626880). Its transcription is activated upon sterol deprivation by SREBP-2 acting through two promoter sterol-regulatory elements with adjacent NF-Y sites (PMID:28342963), and is further controlled by an extensive regulatory network: MYC induces SQLE directly and through its target AP4/TFAP4 (PMID:33791309, PMID:37705742), SP1 binds and activates the promoter (PMID:39946769), and KDM4A-mediated H3K9me3 demethylation opens the locus to permit GABPA binding (PMID:39461328), while p53 represses SQLE both directly and via miR-205, which targets SQLE mRNA (PMID:34459531, PMID:34417456, PMID:37705742). SQLE is also regulated at the RNA level through stabilizing m5C and ac4C modifications (PMID:40536094, PMID:41550764). Post-translationally, SQLE is degraded by ERAD upon cholesterol excess through MARCH6-mediated ubiquitylation using UBE2J2 as its E2, a process governed by the circular transmembrane architecture of MARCH6 that couples lipid sensing, substrate channeling, and RING activity (PMID:30658189, PMID:32755570, PMID:38195637). Beyond catalysis, SQLE drives oncogenic phenotypes through both its substrate and product: blocking the enzyme causes toxic squalene accumulation that triggers ER stress and apoptosis and reprograms the tumor microenvironment via NF-κB/CXCL1-dependent immune cell recruitment (PMID:30626880, PMID:37542052, PMID:39763673), whereas its product 2,3-oxidosqualene engages vinculin to promote YAP1 nuclear accumulation and YAP/TEAD signaling (PMID:39924077). SQLE additionally localizes to mitochondria, where it interacts with LONP1 to stabilize TFAM and elevate oxidative phosphorylation (PMID:41254141). Through these activities SQLE is broadly oncogenic and a tractable drug target, with the inhibitor terbinafine suppressing tumor growth and synergizing with anti-PD1 immunotherapy (PMID:34417456, PMID:41005980).

Mechanistic history

Synthesis pass · year-by-year structured walk · 19 steps
  1. 1997 Medium

    Establishing the genomic location and sterol-responsiveness of human SQLE defined it as a regulated component of the cholesterol synthesis program, the foundation for all later regulatory work.

    Evidence PCR on somatic/radiation hybrid panels, FISH, and transcriptional regulation assays

    PMID:9286711

    Open questions at the time
    • Promoter elements mediating sterol regulation not yet mapped
    • No mechanism for the regulation defined at this stage
  2. 2017 High

    Mapping two functional SREs and NF-Y sites in the SQLE promoter explained how sterol deprivation drives SQLE transcription through SREBP-2.

    Evidence Luciferase reporter mutagenesis, EMSA, and ChIP-PCR

    PMID:28342963

    Open questions at the time
    • Does not address post-transcriptional or degradative control
    • Other transcription factors at the locus not examined
  3. 2019 High

    Identifying MARCH6 with UBE2J2 as the E3/E2 pair for cholesterol-stimulated SQLE degradation established post-translational, ERAD-dependent control as a second layer of SQLE regulation.

    Evidence CRISPR/Cas9 screen of ERAD E2 enzymes and protein stability/activity-rescue assays in multiple human cell lines

    PMID:30658189

    Open questions at the time
    • Structural basis of MARCH6-SQLE recognition not resolved
    • Degron on SQLE not mapped here
  4. 2019 High

    Showing that SQLE inhibition kills certain neuroendocrine tumors through toxic squalene accumulation rather than cholesterol depletion redefined the enzyme's substrate as a context-dependent cytotoxic metabolite.

    Evidence Chemical biology screen with metabolic tracing, viability assays, and squalene measurements

    PMID:30626880

    Open questions at the time
    • Molecular targets of accumulated squalene not identified
    • Why only a subset of tumors is sensitive not fully explained
  5. 2019 Medium

    Linking OSBPL2 loss to AMPK suppression and increased SP1/SREBF2 promoter occupancy connected upstream lipid-sensing signaling to SQLE transcriptional output.

    Evidence CRISPR knockout HeLa cells, RNA-seq, luciferase reporters, and AMPK inhibitor experiments

    PMID:31356817

    Open questions at the time
    • Direct vs indirect SP1 contribution not separated from SREBF2
    • Generality beyond HeLa not tested
  6. 2020 High

    Demonstrating that the MARCH6-SQLE axis controls endothelial cholesterol load, membrane order, VE-cadherin junctions, and angiogenic sprouting extended SQLE regulation to a physiological cell-biological phenotype.

    Evidence siRNA/shRNA knockdown with cholesterol, membrane order, barrier, and sprouting assays in endothelial cells

    PMID:32755570

    Open questions at the time
    • In vivo vascular relevance not established here
    • Which cholesterol pool drives junction effects unclear
  7. 2021 High

    Defining opposing transcriptional control by tumor-suppressive p53 (direct and via miR-205) and oncogenic MYC placed SQLE at a regulatory junction linking cell-state determinants to cholesterol output.

    Evidence Reporter assays, miRNA restoration, knockdown/overexpression epistasis, terbinafine studies, and in vivo p53-KO NAFLD tumor models

    PMID:33791309 PMID:34417456 PMID:34459531

    Open questions at the time
    • Relative dominance of these regulators in different tissues unclear
    • Crosstalk with SREBP-2 control not fully integrated
  8. 2022 High

    Identifying SQLE as the direct binding target of polyphyllin I established the enzyme as a small-molecule-druggable node within the SREBP-2/HMGCR/SQLE pathway and a mediator of hepatotoxicity.

    Evidence Pull-down, SPR, molecular docking, and knockdown/overexpression of HMGCR and SQLE

    PMID:36820075

    Open questions at the time
    • Binding site on SQLE not mapped at residue level
    • Selectivity over related enzymes not fully characterized
  9. 2023 Medium

    Resolving dual cancer-promoting mechanisms — squalene-driven ER stress/apoptosis on inhibition and lipid-raft-dependent Src/PI3K/Akt activation — clarified how SQLE both maintains and, when blocked, kills tumor cells.

    Evidence siRNA knockdown, inhibitors, ER stress markers, lipid raft fractionation, pathway analysis, and xenografts in pancreatic cancer

    PMID:37542052

    Open questions at the time
    • Direct effector of raft-dependent signaling not isolated
    • Balance between the two mechanisms in vivo unclear
  10. 2023 Medium

    Showing that SQLE inhibition raises squalene to repress NF-κB/CXCL1 and remodel immune infiltration revealed a non-cholesterol, microenvironmental function for the SQLE substrate.

    Evidence SQLE knockdown and squalene administration in immune-competent mice with flow cytometry, RNA-seq, and NF-κB pathway analysis

    PMID:39763673

    Open questions at the time
    • Direct molecular target of squalene upstream of NF-κB not defined
    • Single tumor model
  11. 2023 Medium

    Extending the MYC and p53 networks to the AP4/TFAP4 effector and miR-205 axis, and linking AP4 loss to terbinafine resistance, refined the transcriptional logic governing SQLE-targeted therapy response.

    Evidence miR-205 target validation, AP4 reporter assays, AP4 knockdown/overexpression, and terbinafine sensitivity assays

    PMID:37705742

    Open questions at the time
    • Whether AP4 status predicts clinical drug response untested
    • Interaction with degradation control not addressed
  12. 2024 High

    The cryo-EM structure of MARCH6 with large-scale mutagenesis explained mechanistically how lipid sensing, a transmembrane channel, and RING activity are coupled to drive SQLE degradation.

    Evidence Cryo-EM, AlphaFold modeling, 95-variant mutagenesis, and SQLE stability assays

    PMID:38195637

    Open questions at the time
    • Atomic detail of the SQLE substrate engagement not captured
    • Dynamics of channel gating during turnover not resolved
  13. 2024 Medium

    Defining KDM4A/GABPA chromatin-level activation of SQLE and downstream ROS-JNK/c-Jun signaling added an epigenetic layer to SQLE control with therapeutic implications in bladder cancer.

    Evidence KDM4A inhibitor organoid screening, H3K9me3 and GABPA ChIP, knockdown, ROS measurements, and PDX models

    PMID:39461328

    Open questions at the time
    • Generality of KDM4A-SQLE control across tumor types unknown
    • Direct GABPA dependence vs cofactors not dissected
  14. 2024 High

    Discovering mitochondrial SQLE that binds LONP1 to stabilize TFAM and boost OXPHOS established a moonlighting, catalysis-independent role outside the ER cholesterol pathway.

    Evidence Subcellular fractionation, SQLE-LONP1 Co-IP, TFAM stability and OXPHOS/ROS assays, transgenic/KO mice, and Mito-TEMPO rescue

    PMID:41254141

    Open questions at the time
    • How SQLE is targeted to mitochondria not defined
    • Whether enzymatic activity is required for TFAM stabilization unclear
  15. 2024 Medium

    Showing that accumulated squalene binds Sp1 to form an Sp1-TFAP2E promoter complex suppressing PGC-1α revealed a second non-cholesterol mechanism by which SQLE substrate restrains mitochondrial biogenesis.

    Evidence SQLE silencing, in vivo squalene administration, Sp1-DNA binding analysis, and TFAP2E/PGC-1α expression assays in xenografts

    PMID:40015662

    Open questions at the time
    • Direct squalene-Sp1 binding biophysics not shown
    • Reconciliation with mitochondrial OXPHOS-promoting role of SQLE not addressed
  16. 2025 Medium

    Connecting SQLE activity to palmitoyl-CoA-driven PD-L1 palmitoylation downstream of H. pylori CagA linked the enzyme's lipid metabolism to immune-checkpoint stabilization and immune evasion.

    Evidence CagA overexpression, SQLE manipulation, palmitoyl-CoA measurement, and PD-L1 palmitoylation/ubiquitination and T-cell assays

    PMID:39809787

    Open questions at the time
    • Enzymatic route from SQLE to palmitoyl-CoA pools not fully traced
    • In vivo relevance to infection-associated cancer untested here
  17. 2025 Medium

    Identifying RNA modifications (m5C by NSUN2, ac4C by NAT10) and additional transcription factors (YY1, SP1) as SQLE regulators expanded the regulatory network to mRNA stability and further signaling inputs across disease contexts.

    Evidence NSUN2/NAT10 manipulation with m5C/ac4C and mRNA stability assays; YY1 and SP1 ChIP/reporter assays with PI3K-AKT and AKT/mTOR pathway analysis

    PMID:39946769 PMID:40536094 PMID:40614853 PMID:41550764

    Open questions at the time
    • Relative quantitative contribution of each input not benchmarked
    • Crosstalk among RNA modifications and transcriptional control not integrated
  18. 2025 Medium

    Showing that the SQLE product 2,3-oxidosqualene binds vinculin to drive YAP1 nuclear accumulation identified a product-based signaling output coupling SQLE to YAP/TEAD oncogenic transcription.

    Evidence ESCC cohort sequencing, 2,3-oxidosqualene/vinculin interaction studies, YAP localization assays, and in vivo 4-NQO ESCC mouse model

    PMID:39924077

    Open questions at the time
    • Structural basis of 2,3-oxidosqualene-vinculin binding not resolved
    • Generality beyond ESCC unknown
  19. 2025 Medium

    Demonstrating that SQLE inhibition reduces tumor 27-hydroxycholesterol secretion to relieve cholesterol restriction on CD8+ T cells positioned SQLE blockade, including terbinafine plus anti-PD1, as an immunotherapy-sensitizing strategy.

    Evidence Pharmacological and genetic SQLE inhibition, tumor-T cell co-culture, untargeted metabolomics, and murine HCC anti-PD1 combination models

    PMID:41005980

    Open questions at the time
    • Human clinical efficacy of the combination not established
    • Direct vs indirect oxysterol effects on T cells not fully separated

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how SQLE's enzymatic and non-enzymatic (mitochondrial LONP1/TFAM-stabilizing) roles, its substrate- and product-based signaling outputs, and its layered transcriptional/RNA/degradative regulation are integrated and prioritized within a single cell.
  • No unified model coupling ER catalysis, mitochondrial moonlighting, and metabolite signaling
  • Mechanism of SQLE mitochondrial targeting unknown
  • Direct molecular targets of squalene and 2,3-oxidosqualene incompletely mapped

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016491 oxidoreductase activity 2 GO:0016787 hydrolase activity 2
Localization
GO:0005783 endoplasmic reticulum 2 GO:0005739 mitochondrion 1
Pathway
R-HSA-1430728 Metabolism 3 R-HSA-1643685 Disease 3 R-HSA-168256 Immune System 3
Partners
FDFT1LONP1MARCH6UBE2J2

Evidence

Reading pass · 25 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1997 Human SQLE was mapped to chromosome 8q24.1 by PCR on somatic cell hybrid panels and FISH, and was shown to be transcriptionally regulated by sterols and cholesterol synthesis inhibitors. PCR on somatic cell hybrid panel, radiation hybrid panel, fluorescence in situ hybridization (FISH), transcriptional regulation assays Genomics Medium 9286711
2017 The human SQLE promoter contains two sterol-regulatory elements (SREs) and two NF-Y binding sites that mediate SREBP-2-dependent transcriptional activation of SQLE in response to sterol deprivation. Luciferase reporter assays with SRE/NF-Y site mutants, electrophoretic mobility shift assay (EMSA), ChIP-PCR Biochimica et biophysica acta. Molecular and cell biology of lipids High 28342963
2018 MARCH6 (an E3 ubiquitin ligase) promotes cholesterol-stimulated ubiquitylation and proteasomal degradation of SQLE, and UBE2J2 (not UBE2G2) is the primary E2 ubiquitin-conjugating enzyme required for this MARCH6-dependent SQLE degradation in mammalian cells, including hepatic cells. CRISPR/Cas9 screen of ERAD-associated E2 enzymes, protein stability assays, enzymatic activity-dependent rescue experiments in multiple human cell lines Atherosclerosis High 30658189
2019 Sensitivity to SQLE inhibition in a subset of neuroendocrine tumors (particularly small cell lung cancer) results from toxic accumulation of the SQLE substrate squalene, not from downstream cholesterol biosynthesis inhibition. Chemical biology screen, orthogonal metabolic and cell viability assays, squalene accumulation measurements Nature communications High 30626880
2019 OSBPL2 deletion upregulates SQLE expression via suppression of the AMPK signaling pathway, which leads to increased SP1 and SREBF2 nuclear entry and binding to functional sites in the SQLE promoter, resulting in elevated intracellular cholesterol and cholesteryl ester. CRISPR/Cas9 OSBPL2 knockout HeLa cells, RNA-seq, dual-luciferase reporter assay, AMPK pathway inhibitor experiments Experimental cell research Medium 31356817
2020 MARCH6 promotes degradation of SQLE in endothelial cells to regulate cholesterol load; loss of MARCH6 increases SQLE protein and cholesterol, altering membrane order, disorganizing VE-cadherin-based adherens junctions, and impairing angiogenic sprouting. siRNA/shRNA knockdown of MARCHF6 and SQLE, cholesterol measurements, membrane order assays, barrier function assays, endothelial sprouting assays Cell reports High 32755570
2021 p53 directly represses SQLE transcription in a SREBP2-independent manner under normal sterol conditions, thereby reducing cholesterol production and suppressing tumor growth; SQLE inhibition reverses the increased cell proliferation caused by p53 deficiency. Transcriptional reporter assays, siRNA/shRNA knockdown, terbinafine inhibitor studies, in vivo mouse NAFLD tumorigenesis model with p53 KO EMBO reports High 34459531
2021 MYC directly transcriptionally upregulates SQLE, thereby increasing cholesterol biosynthesis and promoting tumor cell proliferation; SQLE overexpression restores cholesterol levels in MYC-knockdown cells, and enforced MYC expression has no effect on cholesterol in SQLE-depleted cells. MYC knockdown/overexpression, SQLE overexpression rescue, cholesterol measurements, epistasis experiments Frontiers in cell and developmental biology Medium 33791309
2021 miR-205 directly targets SQLE mRNA to repress its expression and inhibit de novo cholesterol biosynthesis in prostate cancer; inhibition of SQLE blocks AR pathway transactivation and suppresses tumor growth in vivo. miR-205 restoration, SQLE competitive inhibition with terbinafine, cholesterol biosynthesis assays, in vivo orthotopic tumor model, patient PSA measurement Nature communications High 34417456
2022 Polyphyllin I (PPI) directly binds SQLE protein (not HMGCR), disrupting the SREBP-2/HMGCR/SQLE/lanosterol synthase cholesterol biosynthesis pathway and inducing hepatotoxicity. Pull-down assay, surface plasmon resonance (SPR), molecular docking, siRNA knockdown and overexpression of HMGCR and SQLE, proteomics/transcriptomics Journal of pharmaceutical analysis High 36820075
2023 SQLE inhibition in pancreatic cancer cells leads to squalene accumulation that inhibits CXCL1 transcription via the NF-κB/p65 pathway, reducing recruitment of MDSCs and TAMs and increasing CD8+ T cell infiltration in the tumor microenvironment. SQLE knockdown in immune-competent mouse model, squalene administration in vivo, flow cytometry of immune cells, RNA-sequencing, RT-PCR/Western blot for NF-κB pathway Frontiers in immunology Medium 39763673
2023 SQLE promotes pancreatic cancer growth through two mechanisms: (1) its inhibition causes squalene accumulation-induced ER stress and apoptosis; (2) SQLE-mediated cholesterol biosynthesis maintains lipid raft stability, activating the Src/PI3K/Akt signaling pathway. siRNA knockdown, SQLE inhibitors, ER stress markers, lipid raft fractionation, Src/PI3K/Akt pathway analysis, xenograft tumor models Cell death & disease Medium 37542052
2023 p53 suppresses SQLE expression via induction of miR-205, which directly targets SQLE mRNA; c-MYC induces SQLE expression directly and via its transcriptional target AP4/TFAP4, which directly binds the SQLE promoter; loss of AP4 causes resistance to terbinafine. miR-205 target validation, AP4/TFAP4 transcriptional reporter assays, AP4 knockdown/overexpression, cholesterol measurements, terbinafine sensitivity assays International journal of biological sciences Medium 37705742
2024 Doa10/MARCH6 adopts a unique circular transmembrane structure with a lipid-binding scaffold and gated helical bundle; the RING domain is positioned over the membrane channel, and SQLE degradation requires interconnected channel, RING domain, and lipid-binding elements, revealing how metabolic signals, substrate binding, and E3 ligase activity are coupled. Cryo-EM structural analysis, AlphaFold predictions, structure-based mutagenesis campaign (95 MARCH6 variants), SQLE stability assays Nature communications High 38195637
2024 KDM4A histone demethylase demethylates H3K9me3 at the SQLE gene locus, opening chromatin to allow GABPA transcription factor binding and SQLE transcriptional activation; KDM4A inhibition downregulates SQLE, blocks cholesterol synthesis, causes squalene accumulation, suppresses JNK/c-Jun phosphorylation via ROS, and induces apoptosis in bladder cancer. KDM4A inhibitor (ML324) drug screening in tumor organoids, ChIP assays for H3K9me3 and GABPA, SQLE knockdown, ROS measurements, JNK/c-Jun pathway analysis, PDX models Redox biology Medium 39461328
2024 SQLE localizes to mitochondria and directly interacts with LONP1 (Lon peptidase 1) to stabilize mitochondrial transcription factor A (TFAM) by preventing its proteolysis, leading to elevated oxidative phosphorylation (OXPHOS) and mitochondrial ROS production in bladder cancer cells. Subcellular fractionation/localization studies, co-immunoprecipitation of SQLE-LONP1 interaction, TFAM stability assays, OXPHOS and mitochondrial ROS measurements, Sqle transgenic and knockout mouse models, Mito-TEMPO rescue experiments Oncogene High 41254141
2024 SQLE-mediated removal of squalene promotes mitochondrial biogenesis via a non-cholesterol mechanism: squalene accumulation binds Sp1 protein and forms a tight Sp1-TFAP2E promoter complex, suppressing TFAP2E and downstream PGC-1α expression, thereby inhibiting mitochondrial metabolism and tumor formation. SQLE silencing, squalene direct administration in vivo, Sp1-DNA binding analysis (binding score calculation), TFAP2E/PGC-1α expression assays, xenograft tumor model, pharmacological squalene administration Cancer letters Medium 40015662
2025 H. pylori CagA upregulates SQLE expression, and elevated SQLE activity increases cellular palmitoyl-CoA levels, which enhances PD-L1 palmitoylation while decreasing its ubiquitination, thereby stabilizing PD-L1 and suppressing T cell activity to facilitate immune evasion. CagA overexpression, SQLE manipulation, palmitoyl-CoA measurement, PD-L1 palmitoylation and ubiquitination assays, T cell activity assays Cell death & disease Medium 39809787
2025 HDAC2-dependent delactylation of PD-L1 at K189 promotes vimentin-mediated nuclear translocation of PD-L1, which then upregulates SQLE transcription via the transcription factor YY1, thereby accelerating cholesterol production and liver cancer growth. PD-L1 lactylation site mapping, p300 acetyltransferase activity assays, HDAC2 deacylation assays, nuclear fractionation, YY1 ChIP/reporter assays for SQLE promoter, in vitro and in vivo tumor growth assays Cancer letters Medium 40614853
2025 NSUN2 increases m5C modification of SQLE mRNA, stabilizing it and increasing SQLE expression in endothelial cells; elevated SQLE increases intracellular cholesterol, which promotes endothelial cell activation via the PI3K-AKT signaling pathway in diabetic retinopathy. NSUN2 knockdown/overexpression, m5C modification assays, SQLE mRNA stability measurements, cholesterol quantification, PI3K-AKT pathway analysis, tube formation and endothelial activation assays FASEB journal Medium 40536094
2025 NAT10 acts as an upstream activator of SQLE-dependent cholesterol biosynthesis through two mechanisms: (1) activation of AKT/mTOR signaling leading to SQLE upregulation, and (2) ac4C modification of SQLE mRNA to enhance its stability. Multi-omics dataset analysis, AKT/mTOR pathway manipulation, ac4C mRNA modification assays, SQLE mRNA stability measurements, in vitro and in vivo cholesterol and tumor growth assays iScience Medium 41550764
2025 SP1 directly binds to the SQLE promoter and activates its transcription, as demonstrated in the context of SERPINH1/SENP3 signaling in hepatocellular carcinoma. ChIP-qPCR assay demonstrating SP1 binding to SQLE promoter, SP1 inhibitor (plicamycin) rescue experiments International immunopharmacology Medium 39946769
2025 SQLE-produced intermediate metabolite 2,3-oxidosqualene interacts with vinculin to enhance nuclear accumulation of YAP1, increasing YAP/TEAD-dependent gene expression and accelerating tumor growth and metastasis in esophageal squamous cell carcinoma. Whole genome sequencing of ESCC cohorts, metabolite-protein interaction studies (2,3-oxidosqualene/vinculin), YAP nuclear localization assays, in vivo 4-NQO mouse ESCC model with SQLE overexpression Cancer letters Medium 39924077
2025 SQLE inhibition in hepatocellular carcinoma tumor cells suppresses oxysterol (27-hydroxycholesterol) secretion, overcoming cholesterol restrictions on CD8+ T cells via oxysterol-SREBP2 signaling and enhancing antitumor immunity; terbinafine synergizes with anti-PD1 therapy in HCC mouse models. Pharmacological SQLE inhibition and genetic knockdown, co-culture experiments of tumor cells and T cells, untargeted metabolomics identifying 27-hydroxycholesterol, transcriptome analysis, murine HCC models with anti-PD1 combination therapy Journal for immunotherapy of cancer Medium 41005980
2025 Ginsenoside 20(S)-Rg3 upregulates SQLE expression by downregulating HIF-1α, and SQLE interacts with FDFT1 (farnesyl-diphosphate farnesyltransferase 1) as confirmed by co-immunoprecipitation. Co-immunoprecipitation of SQLE-FDFT1 interaction, HIF-1α/SQLE axis manipulation, transcriptomic and lipidomic analysis, SQLE silencing rescue experiments iScience Low 40792023

Source papers

Stage 0 corpus · 62 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2020 Emergence of Terbinafine Resistant Trichophyton mentagrophytes in Iran, Harboring Mutations in the Squalene Epoxidase (SQLE) Gene. Infection and drug resistance 102 32214830
2023 SQLE promotes pancreatic cancer growth by attenuating ER stress and activating lipid rafts-regulated Src/PI3K/Akt signaling pathway. Cell death & disease 78 37542052
2020 A Novel Long Non-Coding RNA lnc030 Maintains Breast Cancer Stem Cell Stemness by Stabilizing SQLE mRNA and Increasing Cholesterol Synthesis. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 77 33511005
2017 New insights into cellular cholesterol acquisition: promoter analysis of human HMGCR and SQLE, two key control enzymes in cholesterol synthesis. Biochimica et biophysica acta. Molecular and cell biology of lipids 75 28342963
2021 MiR-205-driven downregulation of cholesterol biosynthesis through SQLE-inhibition identifies therapeutic vulnerability in aggressive prostate cancer. Nature communications 66 34417456
2019 A chemical biology screen identifies a vulnerability of neuroendocrine cancer cells to SQLE inhibition. Nature communications 64 30626880
2021 p53 transcriptionally regulates SQLE to repress cholesterol synthesis and tumor growth. EMBO reports 63 34459531
2015 Squalene epoxidase (SQLE) promotes the growth and migration of the hepatocellular carcinoma cells. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 57 25787749
2020 Belgian National Survey on Tinea Capitis: Epidemiological Considerations and Highlight of Terbinafine-Resistant T. mentagrophytes with a Mutation on SQLE Gene. Journal of fungi (Basel, Switzerland) 52 33003309
2019 A new mutation in the SQLE gene of Trichophyton mentagrophytes associated to terbinafine resistance in a couple with disseminated tinea corporis. Journal de mycologie medicale 48 31611164
1997 Localization of the squalene epoxidase gene (SQLE) to human chromosome region 8q24.1. Genomics 40 9286711
2017 SQLE induces epithelial-to-mesenchymal transition by regulating of miR-133b in esophageal squamous cell carcinoma. Acta biochimica et biophysica Sinica 38 28069586
2022 Phylogeny, Antifungal Susceptibility, and Point Mutations of SQLE Gene in Major Pathogenic Dermatophytes Isolated From Clinical Dermatophytosis. Frontiers in cellular and infection microbiology 33 35372131
2018 Differential use of E2 ubiquitin conjugating enzymes for regulated degradation of the rate-limiting enzymes HMGCR and SQLE in cholesterol biosynthesis. Atherosclerosis 32 30658189
2019 OSBPL2 deficiency upregulate SQLE expression increasing intracellular cholesterol and cholesteryl ester by AMPK/SP1 and SREBF2 signalling pathway. Experimental cell research 30 31356817
2021 MYC Enhances Cholesterol Biosynthesis and Supports Cell Proliferation Through SQLE. Frontiers in cell and developmental biology 29 33791309
2025 Helicobacter pylori CagA promotes gastric cancer immune escape by upregulating SQLE. Cell death & disease 26 39809787
2022 The interaction between polyphyllin I and SQLE protein induces hepatotoxicity through SREBP-2/HMGCR/SQLE/LSS pathway. Journal of pharmaceutical analysis 25 36820075
2020 The MARCH6-SQLE Axis Controls Endothelial Cholesterol Homeostasis and Angiogenic Sprouting. Cell reports 23 32755570
2020 Estrogen Abolishes the Repression Role of gga-miR-221-5p Targeting ELOVL6 and SQLE to Promote Lipid Synthesis in Chicken Liver. International journal of molecular sciences 22 32120850
2022 Iranian National Survey on Tinea Capitis: Antifungal Susceptibility Profile, Epidemiological Characteristics, and Report of Two Strains with a Novel Mutation in SQLE Gene with Homology Modeling. Mycopathologia 21 35980496
2022 Downregulated ferroptosis-related gene SQLE facilitates temozolomide chemoresistance, and invasion and affects immune regulation in glioblastoma. CNS neuroscience & therapeutics 20 35962621
2024 SCD1 promotes the stemness of gastric cancer stem cells by inhibiting ferroptosis through the SQLE/cholesterol/mTOR signalling pathway. International journal of biological macromolecules 19 38972654
2024 Inhibition of KDM4A restricts SQLE transcription and induces oxidative stress imbalance to suppress bladder cancer. Redox biology 19 39461328
2022 SQLE facilitates the pancreatic cancer progression via the lncRNA-TTN-AS1/miR-133b/SQLE axis. Journal of cellular and molecular medicine 18 35638462
2022 SQLE inhibition suppresses the development of pancreatic ductal adenocarcinoma and enhances its sensitivity to chemotherapeutic agents in vitro. Molecular biology reports 17 35552960
2021 SQLE Mediates Metabolic Reprogramming to Promote LN Metastasis in Castration-Resistant Prostate Cancer. OncoTargets and therapy 17 34335030
2024 Doa10/MARCH6 architecture interconnects E3 ligase activity with lipid-binding transmembrane channel to regulate SQLE. Nature communications 14 38195637
2023 Squalene epoxidase/SQLE is a candidate target for treatment of colorectal cancers with p53 mutation and elevated c-MYC expression. International journal of biological sciences 14 37705742
2023 SQLE Knockdown inhibits bladder cancer progression by regulating the PTEN/AKT/GSK3β signaling pathway through P53. Cancer cell international 14 37770925
2023 Treatment recalcitrant cases of tinea corporis/cruris caused by T. mentagrophytes - interdigitale complex with mutations in ERG11 ERG 3, ERG4, MDR1 MFS genes & SQLE and their potential implications. International journal of dermatology 13 36929499
2024 Epidemiological trends, antifungal drug susceptibility and SQLE point mutations in etiologic species of human dermatophytosis in Al-Diwaneyah, Iraq. Scientific reports 12 38830918
2025 PD-L1 delactylation-promoted nuclear translocation accelerates liver cancer growth through elevating SQLE transcription activity. Cancer letters 11 40614853
2023 Knockdown of SQLE promotes CD8+ T cell infiltration in the tumor microenvironment. Cellular signalling 11 37993027
2023 Circ_0000182 promotes cholesterol synthesis and proliferation of stomach adenocarcinoma cells by targeting miR-579-3p/SQLE axis. Discover oncology 10 36808302
2025 SERPINH1 secretion by cancer-associated fibroblasts promotes hepatocellular carcinoma malignancy through SENP3-mediated SP1/SQLE pathway. International immunopharmacology 9 39946769
2024 Squalene monooxygenase (SQLE) protects ovarian cancer cells from ferroptosis. Scientific reports 9 39349544
2024 Stabilization of SQLE mRNA by WTAP/FTO/IGF2BP3-dependent manner in HGSOC: implications for metabolism, stemness, and progression. Cell death & disease 7 39617776
2020 SQLE Promotes Differentiation and Apoptosis of Bovine Skeletal Muscle-Derived Mesenchymal Stem Cells. Cellular reprogramming 6 32011919
2025 Succinate supplementation alleviates liver cancer by inhibiting the FN1/SQLE axis-mediated cholesterol biosynthesis. iScience 5 39898026
2025 Ginsenoside 20(S)-Rg3 upregulates SQLE to reprogram cholesterol metabolism of ovarian cancer cells. iScience 5 40792023
2025 Targeting SQLE-mediated cholesterol metabolism to enhance CD8+ T cell activation and immunotherapy efficacy in hepatocellular carcinoma. Journal for immunotherapy of cancer 5 41005980
2024 SQLE-mediated squalene metabolism promotes tumor immune evasion in pancreatic cancer. Frontiers in immunology 5 39763673
2025 SQLE-catalyzed squalene metabolism promotes mitochondrial biogenesis and tumor development in K-ras-driven cancer. Cancer letters 4 40015662
2025 Fangchinoline suppresses nasopharyngeal carcinoma progression by inhibiting SQLE to regulate the PI3K/AKT pathway dysregulation. Phytomedicine : international journal of phytotherapy and phytopharmacology 4 40090046
2021 Corrigendum: MYC Enhances Cholesterol Biosynthesis and Supports Cell Proliferation Through SQLE. Frontiers in cell and developmental biology 4 34179026
2025 SQLE drives bladder cancer progression by boosting mitochondrial oxidative phosphorylation. Oncogene 3 41254141
2024 SQLE promotes osteosarcoma progression via activating TGFβ/SMAD signaling pathway. Molecular and cellular probes 3 39608425
2026 SQLE mutations and antifungal susceptibility profile of Trichophyton species isolated from patients with recalcitrant dermatophytosis: A laboratory-based study from Pakistan. Medical mycology 1 41481143
2025 SQLE amplification accelerates esophageal squamous cell carcinoma tumorigenesis and metastasis through oncometabolite 2,3-oxidosqualene repressing Hippo pathway. Cancer letters 1 39924077
2025 FOXM1 boosts glycolysis by upregulating SQLE to inhibit anoikis in breast cancer cells. Journal of cancer research and clinical oncology 1 40360780
2025 Dynamics of Sqle under electric field exposure. Biochemical and biophysical research communications 1 40382843
2025 Etiology-based Molecular Characterization of Hepatocellular Carcinoma Reveals SQLE's Contribution to Immunosuppressive Microenvironment. Current cancer drug targets 1 40415319
2025 Identification and validation of SQLE in steroid-induced osteonecrosis of the femoral head: a bioinformatics and experimental study. Journal of orthopaedic surgery and research 1 41107894
2023 Novel Insight into the Role of Squalene Epoxidase (SQLE) Gene in Determining Milk Production Traits in Buffalo. International journal of molecular sciences 1 36768756
2023 Hsa_circ_0028007 regulates the progression of nasopharyngeal carcinoma through the miR-1179/SQLE axis. Open medicine (Warsaw, Poland) 1 37554147
2026 Tumor-suppressive SQLE reprograms metabolic flux: Convergence of aerobic glycolysis and cholesterol pathways in ovarian cancer. Experimental cell research 0 41791570
2026 Bletilla striata polysaccharide alleviates obesity by remodeling the gut microbiota-metabolite-liver axis and suppressing the hepatic AMPK-SREBP2/SQLE signaling pathway. International journal of biological macromolecules 0 41833674
2026 METTL7A inhibits progression of colorectal cancer through the SREBP1 / FDFT1 / SQLE / CYP51A1 / cholesterol metabolic pathway. Cellular oncology (Dordrecht, Netherlands) 0 42009961
2026 A Stem Cell-Osteogenesis Axis in Malignant Breast Calcification: SQLE-Driven Reprogramming of Adipose-Derived Mesenchymal Stem Cells. Stem cell reviews and reports 0 42014574
2025 Microglia Promote Endothelial Cell Activation Through NSUN2-Mediated SQLE m5C Modification in Diabetic Retinopathy. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 0 40536094
2025 NAT10 drives hepatocellular carcinoma progression through SQLE-mediated cholesterol biosynthesis and is targetable by remodelin. iScience 0 41550764

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