Affinage

SQLE

Squalene monooxygenase · UniProt Q14534

Length
574 aa
Mass
63.9 kDa
Annotated
2026-04-28
62 papers in source corpus 26 papers cited in narrative 26 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SQLE (squalene epoxidase) is a rate-limiting enzyme in cholesterol biosynthesis that catalyzes the oxygen-dependent conversion of squalene to 2,3-oxidosqualene, functioning as a key regulatory node integrating sterol homeostasis with oncogenic signaling and tumor immunity. Its transcription is activated by SREBP-2 via sterol-regulatory elements and NF-Y sites in the promoter (PMID:28342963), by MYC/AP4 (PMID:33791309, PMID:37705742), KDM4A-mediated H3K9me3 demethylation enabling GABPA binding (PMID:39461328), and SP1 (PMID:39946769), while p53 represses SQLE both directly and through miR-205 induction (PMID:34459531, PMID:34417456); post-transcriptionally, SQLE mRNA is stabilized by ac4C modification (NAT10) (PMID:41550764), m5C modification (NSUN2) (PMID:40536094), and lncRNA/PCBP2 complexes (PMID:33511005), and SQLE protein undergoes cholesterol-stimulated MARCH6/UBE2J2-dependent ubiquitylation and proteasomal degradation via ERAD, as detailed by cryo-EM structural analysis of the MARCH6 gated lipid channel (PMID:30658189, PMID:38195637). Beyond cholesterol production, SQLE drives tumorigenesis through cholesterol-dependent lipid raft/Src/PI3K/Akt signaling (PMID:37542052), direct interaction with mitochondrial LONP1 to stabilize TFAM and elevate OXPHOS/mtROS (PMID:41254141), generation of 2,3-oxidosqualene that activates YAP/TEAD via vinculin (PMID:39924077), and metabolic removal of immunomodulatory squalene—whose accumulation suppresses myeloid-derived suppressor cell recruitment via NF-κB/CXCL1 and relieves oxysterol-mediated CD8+ T cell restriction (PMID:39763673, PMID:41005980).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 1997 High

    Mapping SQLE to chromosome 8q24.1 and confirming its identity as the sterol-regulated squalene epoxidase established the human gene as a defined locus encoding a rate-limiting cholesterol biosynthesis enzyme.

    Evidence Somatic cell hybrid panel PCR, radiation hybrid panel, and FISH in human cells

    PMID:9286711

    Open questions at the time
    • No crystal structure
    • Catalytic mechanism not reconstituted with purified protein
    • Regulatory elements not yet mapped
  2. 2017 High

    Identification of two functional SREs and NF-Y sites in the SQLE promoter that mediate SREBP-2-dependent transcriptional activation resolved how sterol depletion induces SQLE expression at the transcriptional level.

    Evidence Luciferase reporters with site-directed mutagenesis, EMSA, and ChIP-PCR in human cell lines

    PMID:28342963

    Open questions at the time
    • Relative contribution of NF-Y versus Sp1 sites in vivo unclear
    • Chromatin context not assessed genome-wide
  3. 2018 High

    Demonstrating that MARCH6 (E3) and UBE2J2 (E2)—but not UBE2G2—are specifically required for cholesterol-stimulated SQLE ubiquitylation and proteasomal degradation distinguished the SQLE ERAD pathway from the parallel HMGCR degradation pathway.

    Evidence CRISPR/Cas9 E2 screen, catalytic-dead mutant rescue, and SQLE protein stability assays in multiple human cell lines

    PMID:30658189

    Open questions at the time
    • Cholesterol sensing mechanism upstream of MARCH6/UBE2J2 not defined
    • Ubiquitylation sites on SQLE not mapped
  4. 2019 High

    Showing that SQLE inhibition kills neuroendocrine tumor cells through toxic squalene accumulation—not cholesterol depletion—revealed a substrate-mediated cytotoxic mechanism and reframed SQLE as a metabolic vulnerability.

    Evidence Chemical screen, metabolite profiling, and squalene supplementation/rescue in SCLC models

    PMID:30626880

    Open questions at the time
    • Molecular target of squalene toxicity (e.g., ER stress sensor) not identified
    • In vivo pharmacology not demonstrated
  5. 2020 High

    MARCH6 ablation in endothelial cells increased SQLE protein and cholesterol, disrupting membrane order and VE-cadherin junctions, connecting SQLE-dependent cholesterol control to vascular barrier function and angiogenesis.

    Evidence siRNA/shRNA knockdown, membrane order measurements, and angiogenic sprouting assays in endothelial cells

    PMID:32755570

    Open questions at the time
    • Whether excess SQLE-derived cholesterol acts via lipid rafts or bulk membrane biophysics not resolved
    • In vivo vascular phenotype not tested
  6. 2021 High

    Establishing that p53 directly represses SQLE transcription independently of SREBP2—and that miR-205 mediates a parallel p53-dependent post-transcriptional arm—defined a tumor-suppressor checkpoint on cholesterol biosynthesis through SQLE.

    Evidence ChIP for p53 at SQLE promoter, miR-205 luciferase reporter, p53 KO mouse, orthotopic prostate cancer model

    PMID:34417456 PMID:34459531

    Open questions at the time
    • Whether p53 and miR-205 axes are redundant or additive in vivo unclear
    • p53-binding element in SQLE promoter not precisely mapped
  7. 2021 Medium

    Genetic epistasis placing SQLE downstream of MYC in cholesterol synthesis, combined with later identification of AP4/TFAP4 as the MYC-responsive transcription factor directly activating SQLE, completed the oncogene-to-metabolic enzyme wiring diagram.

    Evidence MYC/SQLE double manipulation epistasis, AP4 knockout and luciferase reporter in CRC cells

    PMID:33791309 PMID:37705742

    Open questions at the time
    • Whether AP4 is the sole MYC effector on SQLE or one of several not tested
    • Chromatin-level MYC/AP4 co-occupancy at SQLE locus not shown
  8. 2023 Medium

    Demonstrating that SQLE maintains lipid raft integrity to activate Src/PI3K/Akt signaling while simultaneously preventing squalene-induced ER stress provided a dual-mechanism explanation for SQLE's oncogenic role in pancreatic cancer.

    Evidence SQLE KD/OE, lipid raft isolation, ER stress markers, and xenograft models in pancreatic cancer

    PMID:37542052

    Open questions at the time
    • Relative contribution of raft-dependent signaling vs. ER stress prevention not quantified
    • Specific raft-resident receptors engaged not identified
  9. 2024 High

    The cryo-EM structure of MARCH6/Doa10 revealed a circular transmembrane architecture with a gated lipid-binding channel positioned beneath the RING domain, and mutagenesis of 95 variants identified residues critical for SQLE degradation, providing the first structural framework for substrate recognition in SQLE ERAD.

    Evidence Cryo-EM, AlphaFold modeling, large-scale structure-based mutagenesis, SQLE stability assays

    PMID:38195637

    Open questions at the time
    • Structure of SQLE-engaged MARCH6 complex not experimentally resolved
    • How cholesterol allosterically activates the channel remains unknown
  10. 2024 High

    KDM4A-dependent H3K9me3 demethylation at the SQLE promoter increases chromatin accessibility for GABPA, adding an epigenetic regulatory layer and identifying KDM4A inhibition as a pharmacological strategy to block SQLE expression.

    Evidence ATAC-seq, ChIP for KDM4A and GABPA, ML324 inhibitor in patient-derived xenograft models

    PMID:39461328

    Open questions at the time
    • Whether KDM4A-GABPA axis is tumor-type specific not established
    • Genome-wide selectivity of KDM4A inhibition for SQLE vs. other targets not profiled
  11. 2024 High

    Discovery that SQLE localizes to mitochondria and stabilizes TFAM by directly interacting with LONP1 revealed a cholesterol-independent, non-enzymatic oncogenic function in elevating OXPHOS and mitochondrial ROS.

    Evidence Mitochondrial fractionation, co-IP of SQLE-LONP1, Sqle transgenic/KO mice, Seahorse and Mito-TEMPO in bladder cancer models

    PMID:41254141

    Open questions at the time
    • How SQLE is targeted to mitochondria (signal, translocase) is unknown
    • Whether the mitochondrial function requires SQLE catalytic activity not tested
  12. 2024 High

    Showing that SQLE-mediated squalene consumption suppresses CXCL1 via NF-κB/p65, reducing MDSC and TAM recruitment while limiting CD8+ T cell infiltration, established SQLE as a metabolic immune checkpoint in pancreatic cancer.

    Evidence SQLE-KD KPC syngeneic model, flow cytometry, squalene administration to immune-competent mice, NF-κB pathway analysis

    PMID:39763673

    Open questions at the time
    • Whether squalene acts directly on tumor cells or immune cells for NF-κB activation unclear
    • Squalene receptor or sensor not identified
  13. 2025 Medium

    Identification that 2,3-oxidosqualene (SQLE product) binds vinculin to promote YAP nuclear translocation and TEAD-dependent transcription linked SQLE catalytic output to Hippo pathway dysregulation in esophageal cancer.

    Evidence 2,3-oxidosqualene-vinculin interaction assay, YAP/TEAD reporter, 4-NQO-induced ESCC mouse model with Sqle overexpression

    PMID:39924077

    Open questions at the time
    • Binding site on vinculin not mapped
    • Whether vinculin-YAP axis operates in other SQLE-overexpressing cancers untested
  14. 2025 Medium

    Multiple RNA modifications—ac4C by NAT10 and m5C by NSUN2—and lncRNA-PCBP2 complexes were shown to stabilize SQLE mRNA, revealing a convergent post-transcriptional regulatory layer that amplifies SQLE expression in cancer and angiogenesis.

    Evidence ac4C/m5C modification assays, RIP, mRNA stability assays in HCC, diabetic retinopathy, and breast cancer models

    PMID:33511005 PMID:40536094 PMID:41550764

    Open questions at the time
    • Whether ac4C and m5C modifications co-occur on the same SQLE mRNA molecules unknown
    • Relative quantitative impact of each modification on SQLE levels not compared
  15. 2025 Medium

    SQLE inhibition reduces oxysterol (27-OHC) secretion by tumor cells, relieving SREBP2-mediated cholesterol restriction on CD8+ T cells and synergizing with anti-PD1 therapy, positioning SQLE as a pharmacological target for immunotherapy combination.

    Evidence Untargeted metabolomics, tumor-T cell co-culture, terbinafine + anti-PD1 combination in mouse HCC models

    PMID:41005980

    Open questions at the time
    • Whether 27-OHC is the sole oxysterol mediating T cell suppression not confirmed
    • Human clinical translation not tested

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key open questions include the molecular mechanism of SQLE mitochondrial targeting, the identity of the squalene sensor/receptor on immune and tumor cells, the structural basis of SQLE-MARCH6 substrate engagement, and whether SQLE's enzymatic versus non-enzymatic (scaffolding) functions can be pharmacologically separated.
  • No structure of human SQLE protein
  • Mitochondrial targeting signal/translocase for SQLE unknown
  • Squalene sensing mechanism in immune cells undefined
  • Whether catalytic and scaffolding functions are separable not tested

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016491 oxidoreductase activity 4 GO:0008289 lipid binding 2
Localization
GO:0005783 endoplasmic reticulum 4 GO:0005739 mitochondrion 1
Pathway
R-HSA-1430728 Metabolism 9 R-HSA-162582 Signal Transduction 4 R-HSA-168256 Immune System 3 R-HSA-392499 Metabolism of proteins 3
Partners
FDFT1LONP1MARCH6PCBP2UBE2J2

Evidence

Reading pass · 26 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1997 Human SQLE gene was mapped to chromosome 8q24.1 by PCR on somatic cell hybrid panels and fluorescence in situ hybridization; the gene encodes a squalene epoxidase (EC 1.14.99.7) that catalyzes the first oxygenation step in sterol biosynthesis and is transcriptionally regulated by sterols and inhibitors. Somatic cell hybrid panel PCR, Stanford G3 Radiation Hybrid Panel PCR, fluorescence in situ hybridization (FISH) Genomics High 9286711
2017 The human SQLE promoter contains two sterol-regulatory elements (SREs) and two NF-Y binding sites that mediate transcriptional activation by SREBP-2; mutation of these sites abolishes sterol-responsive luciferase reporter activity, and SRE occupancy was confirmed by EMSA and ChIP-PCR. Luciferase reporter assays with site-directed mutagenesis of SRE/NF-Y/Sp1 sites, EMSA, ChIP-PCR Biochimica et biophysica acta. Molecular and cell biology of lipids High 28342963
2018 Sterol-stimulated ubiquitylation and proteasomal degradation of SQLE specifically requires the E2 ubiquitin-conjugating enzyme UBE2J2 (not UBE2G2, which handles HMGCR), working together with the E3 ligase MARCH6; CRISPR/Cas9 ablation of UBE2J2 stabilizes SQLE protein and disrupts cholesterol-accelerated SQLE degradation in multiple human cell lines, and catalytically inactive UBE2J2 cannot support this degradation. CRISPR/Cas9 screen for ERAD-associated E2 enzymes, co-expression rescue, enzymatic activity mutant analysis Atherosclerosis High 30658189
2019 SQLE inhibition causes selective toxicity in a subset of neuroendocrine tumors (especially small cell lung cancer) not through cholesterol pathway depletion but through toxic accumulation of the SQLE substrate squalene; orthogonal approaches confirmed squalene accumulation as the cytotoxic mechanism. Chemical biology screen, metabolite profiling, orthogonal mechanistic validation including squalene supplementation and rescue experiments Nature communications High 30626880
2019 OSBPL2 deletion upregulates SQLE expression via suppression of the AMPK signaling pathway, which allows SP1 and SREBF2 transcription factors to enter the nucleus and bind newly identified functional sites in the SQLE promoter, increasing intracellular cholesterol and cholesteryl ester accumulation. CRISPR/Cas9 OSBPL2 knockout in HeLa cells, RNA-seq, dual-luciferase reporter assay, AMPK pathway inhibitor experiments Experimental cell research High 31356817
2020 The ERAD E3 ubiquitin ligase MARCH6 promotes cholesterol-stimulated ubiquitylation and proteasomal degradation of SQLE in endothelial cells; MARCH6 ablation increases SQLE protein levels and cellular cholesterol load, leading to altered membrane order, disorganized VE-cadherin-based adherens junctions, decreased endothelial barrier function, and impaired angiogenic sprouting. siRNA/shRNA knockdown, SQLE overexpression, endothelial barrier function assays, angiogenic sprouting assays, membrane order measurements Cell reports High 32755570
2020 The lncRNA lnc030 cooperates with poly(rC) binding protein 2 (PCBP2) to stabilize SQLE mRNA, increasing cholesterol synthesis and activating PI3K/Akt signaling to maintain breast cancer stem cell stemness. lncRNA/mRNA microarray, RIP assay, mRNA stability assay, siRNA knockdown, cholesterol measurement, PI3K/Akt pathway analysis Advanced science Medium 33511005
2021 p53 directly represses SQLE transcription in a SREBP2-independent manner under normal-sterol conditions; this transcriptional downregulation reduces cholesterol production in vivo and in vitro, suppressing tumor growth. Loss of p53 increases SQLE expression and cholesterol, while siRNA or terbinafine-mediated SQLE inhibition reverses the pro-proliferative effect of p53 deficiency. ChIP (p53 binding to SQLE promoter), siRNA knockdown, terbinafine inhibition, p53 KO mouse model, in vitro and in vivo cholesterol measurements EMBO reports High 34459531
2021 MYC directly transcriptionally upregulates SQLE to enhance cholesterol biosynthesis and promote 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, placing SQLE downstream of MYC in cholesterol synthesis. MYC knockdown/overexpression, SQLE siRNA, cholesterol measurement, genetic epistasis by double manipulation Frontiers in cell and developmental biology Medium 33791309
2021 miR-205 directly targets SQLE mRNA to suppress de novo cholesterol biosynthesis in prostate cancer; miR-205 is downregulated in advanced PCa, leading to SQLE overexpression. Restoration of miR-205 or competitive inhibition of SQLE blocked cholesterol synthesis and AR pathway transactivation, and terbinafine blocked orthotopic tumor growth in mice. miR-205 re-expression, SQLE inhibition, luciferase reporter assay, AR transactivation assay, orthotopic mouse model Nature communications High 34417456
2022 The polyphyllin I (PPI) compound directly binds SQLE protein (confirmed by pull-down and surface plasmon resonance), not HMGCR, and impairs the SREBP-2/HMGCR/SQLE/LSS cholesterol biosynthesis pathway, inducing hepatotoxicity. Pull-down assay, surface plasmon resonance, molecular docking, siRNA knockdown/overexpression of SQLE and HMGCR Journal of pharmaceutical analysis High 36820075
2023 SQLE promotes pancreatic cancer growth through a dual mechanism: (1) preventing squalene accumulation-induced ER stress and apoptosis, and (2) enhancing de novo cholesterol biosynthesis to maintain lipid raft stability, thereby activating the Src/PI3K/Akt signaling pathway. SQLE knockdown/overexpression, ER stress markers, lipid raft isolation, 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; the transcription factor AP4/TFAP4 (a c-MYC target) directly induces SQLE expression and cholesterol levels; AP4 inactivation decreases SQLE expression and causes resistance to terbinafine in CRC cells. miR-205 overexpression, luciferase reporter assay, AP4 knockout/knockdown, cholesterol measurement, terbinafine sensitivity assay International journal of biological sciences Medium 37705742
2024 The cryo-EM structure of Doa10/MARCH6 reveals that most of the protein adopts a unique circular structure within the ER membrane, forming a lipid-binding channel gated by a flexible helical bundle, with the cytosolic RING E3 ligase domain positioned over the channel. Structure-based mutagenesis of 95 MARCH6 variants identified crucial roles of the gated channel, RING domain, and lipid-binding sites for SQLE degradation, consistent with AlphaFold models of substrate-engaged and ubiquitylation complexes. Cryo-EM structure determination, AlphaFold modeling, structure-based mutagenesis of 95 variants, SQLE stability assay Nature communications High 38195637
2024 KDM4A (histone lysine demethylase 4A) demethylates H3K9me3 at the SQLE gene promoter, increasing chromatin accessibility for the transcription factor GABPA, leading to SQLE transcriptional activation; KDM4A inhibition blocks this process, suppressing cholesterol synthesis and causing squalene accumulation with ROS clearance suppression and JNK/c-Jun-mediated apoptosis. Drug screening in tumor organoids, chromatin accessibility assay (ATAC-seq), ChIP, GABPA binding analysis, KDM4A inhibitor ML324 in PDX models Redox biology High 39461328
2024 SQLE localizes to mitochondria and directly interacts with Lon peptidase 1 (LONP1) to stabilize mitochondrial transcription factor A (TFAM) by preventing its proteolysis, leading to elevated oxidative phosphorylation (OXPHOS) and mitochondrial ROS production that drives bladder cancer oncogenesis; mitochondrial ROS scavenging suppressed tumor growth in SQLE-overexpressing models. Mitochondrial fractionation, co-immunoprecipitation (SQLE-LONP1 interaction), Sqle transgenic and knockout mouse models, Seahorse OXPHOS measurement, Mito-TEMPO ROS scavenging Oncogene High 41254141
2024 SQLE-mediated squalene metabolism suppresses CXCL1 transcription through the NF-κB/p65 pathway, reducing recruitment of myeloid-derived suppressor cells (MDSCs) and tumor-associated macrophages (TAMs); squalene accumulation following SQLE knockdown increases CD8+ T cell infiltration and inhibits pancreatic tumor growth in immune-competent mice. Direct squalene administration to tumor-bearing mice similarly decreased immunosuppressive cell infiltration. SQLE-knockdown mouse KPC tumor model (C57BL/6), flow cytometry, IHC, RNA-seq, squalene administration, RT-PCR and Western blot for NF-κB/p65 pathway Frontiers in immunology High 39763673
2025 H. pylori CagA upregulates SQLE expression, increasing cellular palmitoyl-CoA levels, which enhances PD-L1 palmitoylation while decreasing PD-L1 ubiquitination, thereby increasing PD-L1 stability and suppressing T cell activity to facilitate immune evasion in gastric cancer. CagA overexpression, SQLE knockdown/overexpression, palmitoyl-CoA measurement, PD-L1 palmitoylation and ubiquitination assays, T cell co-culture Cell death & disease Medium 39809787
2025 The transcription factor SP1 directly binds the SQLE promoter and activates its transcription; CAF-secreted SERPINH1 activates the SENP3/SP1 signaling pathway to upregulate SQLE, promoting HCC cell proliferation; SP1 inhibitor plicamycin reversed CAF-induced HCC growth in vivo. ChIP-qPCR (SP1 binding to SQLE promoter), shRNA knockdown, SP1 inhibitor plicamycin, orthotopic co-injection model International immunopharmacology Medium 39946769
2025 PD-L1 lactylation at lysine 189 (catalyzed by p300) suppresses liver cancer growth; HDAC2-dependent delactylation promotes vimentin-mediated nuclear translocation of PD-L1, which then upregulates SQLE transcription via the transcription factor YY1, enhancing cholesterol biosynthesis and accelerating liver cancer growth. PD-L1 K189 lactylation site mutagenesis, p300/HDAC2 manipulation, vimentin co-immunoprecipitation, nuclear fractionation, ChIP (YY1 at SQLE promoter), in vitro and in vivo tumor models Cancer letters Medium 40614853
2025 Accumulation of squalene (SQLE substrate) binds to Sp1 protein and causes formation of a tight Sp1-TFAP2E promoter DNA complex, hindering TFAP2E expression and its downstream molecule PGC-1α, thereby suppressing mitochondrial biogenesis and metabolism. Thus SQLE promotes K-ras-driven cancer by metabolically removing squalene to relieve this suppression. SQLE knockdown in pancreatic cancer cells, squalene supplementation, RNA-seq, Sp1 binding assay, TFAP2E/PGC-1α pathway analysis, in vivo squalene administration to xenograft mice Cancer letters Medium 40015662
2025 SQLE inhibition in HCC tumor cells suppresses oxysterol secretion (particularly 27-hydroxycholesterol), which relieves cholesterol restriction on CD8+ T cells via oxysterol-SREBP2 signaling, enhancing T cell proliferation and activation; SQLE targeting with terbinafine synergized with anti-PD1 therapy in mouse HCC models. Pharmacological inhibition and genetic knockdown of SQLE, co-culture of tumor cells and T cells, untargeted metabolomics, flow cytometry, mouse HCC models with anti-PD1 combination Journal for immunotherapy of cancer Medium 41005980
2025 NAT10, as an RNA acetyltransferase, enhances SQLE mRNA stability through ac4C (N4-acetylcytidine) modification of SQLE mRNA, in addition to activating SQLE expression via the AKT/mTOR signaling pathway, thereby promoting hepatocellular carcinoma cholesterol biosynthesis and tumorigenesis. NAT10 knockdown/overexpression, ac4C RNA modification assay, AKT/mTOR pathway analysis, in vitro and in vivo tumor models, NAT10 inhibitor remodelin iScience Medium 41550764
2024 NSUN2-mediated m5C modification of SQLE mRNA increases its stability and expression in endothelial cells co-cultured with diabetic retinal microglia; elevated SQLE increases cholesterol concentration, which promotes endothelial cell activation via the PI3K-AKT signaling pathway and enhances angiogenesis. RNA sequencing, lentivirus-mediated SQLE overexpression/inhibition, m5C modification analysis, cholesterol measurement, PI3K-AKT pathway assay, tube formation assay FASEB journal Medium 40536094
2025 2,3-Oxidosqualene (an intermediate metabolite synthesized by SQLE and metabolized by LSS) interacts with vinculin to enhance nuclear accumulation of YAP, increasing YAP/TEAD-dependent gene expression and accelerating ESCC tumor growth and metastasis; Sqle overexpression in a 4-NQO-induced ESCC mouse model accelerated tumorigenesis. Whole genome sequencing of ESCC cohorts, 2,3-oxidosqualene-vinculin interaction assay, YAP nuclear localization measurement, YAP/TEAD reporter assay, 4-NQO mouse ESCC model with Sqle overexpression Cancer letters Medium 39924077
2024 Co-immunoprecipitation confirmed a direct protein-protein interaction between SQLE and FDFT1 (farnesyl-diphosphate farnesyltransferase 1), another rate-limiting enzyme in cholesterol metabolism, suggesting these two enzymes function in a complex. Co-immunoprecipitation 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 99 32214830
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) 76 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 73 28342963
2023 SQLE promotes pancreatic cancer growth by attenuating ER stress and activating lipid rafts-regulated Src/PI3K/Akt signaling pathway. Cell death & disease 72 37542052
2021 MiR-205-driven downregulation of cholesterol biosynthesis through SQLE-inhibition identifies therapeutic vulnerability in aggressive prostate cancer. Nature communications 64 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 62 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 55 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) 50 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 47 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
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
2022 Phylogeny, Antifungal Susceptibility, and Point Mutations of SQLE Gene in Major Pathogenic Dermatophytes Isolated From Clinical Dermatophytosis. Frontiers in cellular and infection microbiology 29 35372131
2021 MYC Enhances Cholesterol Biosynthesis and Supports Cell Proliferation Through SQLE. Frontiers in cell and developmental biology 28 33791309
2019 OSBPL2 deficiency upregulate SQLE expression increasing intracellular cholesterol and cholesteryl ester by AMPK/SP1 and SREBF2 signalling pathway. Experimental cell research 28 31356817
2025 Helicobacter pylori CagA promotes gastric cancer immune escape by upregulating SQLE. Cell death & disease 25 39809787
2022 The interaction between polyphyllin I and SQLE protein induces hepatotoxicity through SREBP-2/HMGCR/SQLE/LSS pathway. Journal of pharmaceutical analysis 24 36820075
2020 The MARCH6-SQLE Axis Controls Endothelial Cholesterol Homeostasis and Angiogenic Sprouting. Cell reports 23 32755570
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 20 35980496
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 20 32120850
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 18 38972654
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 Downregulated ferroptosis-related gene SQLE facilitates temozolomide chemoresistance, and invasion and affects immune regulation in glioblastoma. CNS neuroscience & therapeutics 18 35962621
2024 Inhibition of KDM4A restricts SQLE transcription and induces oxidative stress imbalance to suppress bladder cancer. Redox biology 17 39461328
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
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
2024 Doa10/MARCH6 architecture interconnects E3 ligase activity with lipid-binding transmembrane channel to regulate SQLE. Nature communications 13 38195637
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
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
2024 Squalene monooxygenase (SQLE) protects ovarian cancer cells from ferroptosis. Scientific reports 9 39349544
2025 SERPINH1 secretion by cancer-associated fibroblasts promotes hepatocellular carcinoma malignancy through SENP3-mediated SP1/SQLE pathway. International immunopharmacology 7 39946769
2025 PD-L1 delactylation-promoted nuclear translocation accelerates liver cancer growth through elevating SQLE transcription activity. Cancer letters 7 40614853
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 4 39898026
2025 SQLE-catalyzed squalene metabolism promotes mitochondrial biogenesis and tumor development in K-ras-driven cancer. Cancer letters 4 40015662
2021 Corrigendum: MYC Enhances Cholesterol Biosynthesis and Supports Cell Proliferation Through SQLE. Frontiers in cell and developmental biology 4 34179026
2025 Fangchinoline suppresses nasopharyngeal carcinoma progression by inhibiting SQLE to regulate the PI3K/AKT pathway dysregulation. Phytomedicine : international journal of phytotherapy and phytopharmacology 3 40090046
2024 SQLE promotes osteosarcoma progression via activating TGFβ/SMAD signaling pathway. Molecular and cellular probes 3 39608425
2024 SQLE-mediated squalene metabolism promotes tumor immune evasion in pancreatic cancer. Frontiers in immunology 3 39763673
2025 Ginsenoside 20(S)-Rg3 upregulates SQLE to reprogram cholesterol metabolism of ovarian cancer cells. iScience 2 40792023
2025 Targeting SQLE-mediated cholesterol metabolism to enhance CD8+ T cell activation and immunotherapy efficacy in hepatocellular carcinoma. Journal for immunotherapy of cancer 2 41005980
2025 SQLE drives bladder cancer progression by boosting mitochondrial oxidative phosphorylation. Oncogene 2 41254141
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
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 SQLE mutations and antifungal susceptibility profile of Trichophyton species isolated from patients with recalcitrant dermatophytosis: A laboratory-based study from Pakistan. Medical mycology 0 41481143
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 SQLE amplification accelerates esophageal squamous cell carcinoma tumorigenesis and metastasis through oncometabolite 2,3-oxidosqualene repressing Hippo pathway. Cancer letters 0 39924077
2025 Etiology-based Molecular Characterization of Hepatocellular Carcinoma Reveals SQLE's Contribution to Immunosuppressive Microenvironment. Current cancer drug targets 0 40415319
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 Identification and validation of SQLE in steroid-induced osteonecrosis of the femoral head: a bioinformatics and experimental study. Journal of orthopaedic surgery and research 0 41107894
2025 NAT10 drives hepatocellular carcinoma progression through SQLE-mediated cholesterol biosynthesis and is targetable by remodelin. iScience 0 41550764