Affinage

PLCE1

1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase epsilon-1 · UniProt Q9P212

Length
2302 aa
Mass
258.7 kDa
Annotated
2026-06-10
82 papers in source corpus 20 papers cited in narrative 20 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

PLCE1 (PLCε1) is a phosphoinositide-specific phospholipase C that hydrolyzes PIP2 to generate the second messengers DAG and IP3, coupling receptor signaling to PKC and calcium responses (PMID:40266671, PMID:39325099). In the kidney, PLCE1 is expressed in developing and mature glomerular podocytes, and loss-of-function mutations cause early-onset nephrotic syndrome with diffuse mesangial sclerosis, reflecting arrested glomerular development (PMID:17086182). Mechanistically, PLCE1 organizes podocyte cytoskeletal and motility programs by binding Rac1 and Cdc42 through its PH and Ras-association (RA1/RA2) domains and interacting with NCK2 to sustain active GTP-bound Rho GTPases, EGF/ERK-driven proliferation, and expression of podocyte differentiation markers (PMID:32238860). Beyond development, PLCE1 functions as a context-dependent driver in esophageal squamous cell carcinoma (ESCC), where promoter hypomethylation upregulates it and it engages multiple effector axes: it directly binds p65 and IκBα to promote IκBα/p65 phosphorylation and NF-κB nuclear translocation that activates VEGF-C and Bcl-2 transcription (PMID:30609930), directly binds p53 and MDM2 to promote MDM2-dependent p53 ubiquitination and degradation while stabilizing MDM2 and suppressing autophagy (PMID:32066565), maintains Snail protein to drive invasion and proliferation (PMID:28147304), and activates PKCα/NF-κB signaling (PMID:30450849). PLCE1 also promotes cell-cycle progression through MCM7, both via PKCα-mediated E2F1 phosphorylation that transcriptionally upregulates MCM7 and miR-106b-5p, and by potentiating RIOK2-mediated MCM7 threonine phosphorylation to enable MCM complex assembly and chromatin loading (PMID:38117512). Its catalytic output is restrained by TAK1, which phosphorylates PLCE1 at S1060 to reduce PIP2 hydrolysis and dampen PKC/GSK-3β/β-catenin metastasis signaling (PMID:40266671), and its expression is post-transcriptionally suppressed by miR-145 and miR-328 acting on its 3'UTR (PMID:26657507, PMID:26773497). PLCE1 additionally drives NF-κB/MAPK-dependent inflammation in myocardial ischemia-reperfusion injury (PMID:31217261), doxorubicin-induced cardiomyocyte pyroptosis via mitochondrial dysfunction (PMID:38499110), IP3/Ca2+ signaling and proliferation in hepatic stellate cells (PMID:39325099), and macrophage-intrinsic antibacterial responses to Mycobacterium tuberculosis (PMID:38451080).

Mechanistic history

Synthesis pass · year-by-year structured walk · 9 steps
  1. 2006 High

    Established PLCE1 as a causal gene for a human developmental disorder and placed it in glomerular podocyte biology, answering whether this phospholipase has a defined physiological role.

    Evidence Positional cloning of loss-of-function mutations in nephrotic syndrome patients, podocyte immunofluorescence, IQGAP1 Co-IP, and zebrafish plce1 knockdown

    PMID:17086182

    Open questions at the time
    • Molecular function of the IQGAP1 interaction in podocytes not resolved
    • Whether enzymatic activity versus scaffolding drives the glomerular phenotype not dissected
  2. 2020 High

    Defined how PLCE1 controls podocyte motility and differentiation, linking it mechanistically to Rho-GTPase activation rather than purely lipid hydrolysis.

    Evidence Podocyte knockdown/knockout with GTP-Rac1/Cdc42 pulldowns, domain-mapped interactions, NCK2 Co-IP, migration/proliferation and differentiation-marker assays

    PMID:32238860

    Open questions at the time
    • Whether GTPase regulation requires catalytic PIP2 hydrolysis not determined
    • Connection between NCK2 binding and GTPase activation unresolved
  3. 2017 High

    Demonstrated PLCE1 acts as an oncogenic driver in ESCC by maintaining the invasion transcription factor Snail, moving beyond correlative expression data to causal phenotypes.

    Evidence CRISPR/Cas9 inactivation with in vitro invasion/proliferation assays, xenografts, transcriptomics, and Snail rescue

    PMID:28147304

    Open questions at the time
    • Mechanism by which PLCE1 stabilizes Snail protein not defined
    • Direct versus indirect link to Snail unestablished
  4. 2019 High

    Identified direct protein-binding mechanisms by which PLCE1 controls NF-κB-driven angiogenesis/survival, revealing a non-canonical scaffolding role for the enzyme.

    Evidence Co-IP showing PLCE1-p65 and PLCE1-IκBα binding, phosphorylation and nuclear translocation assays, ChIP at VEGF-C/Bcl-2 promoters, xenografts, MALDI-TOF methylation analysis

    PMID:30609930

    Open questions at the time
    • How PLCE1 binding promotes IκBα/p65 phosphorylation mechanistically unclear
    • Relative contribution of catalytic activity versus direct binding not separated
  5. 2020 High

    Showed PLCE1 directly engages the p53/MDM2 axis to suppress p53 and autophagy, providing a molecular basis for its anti-apoptotic oncogenic activity.

    Evidence Co-IP of PLCE1 with p53 and MDM2, ubiquitination and cycloheximide-chase half-life assays, xenografts with adenoviral p53 rescue

    PMID:32066565

    Open questions at the time
    • Structural basis of PLCE1-MDM2/p53 interaction unknown
    • Whether enzymatic activity is required for MDM2 stabilization not tested
  6. 2024 High

    Resolved how PLCE1 drives cell-cycle progression through dual transcriptional and post-translational control of MCM7, deepening the proliferation mechanism.

    Evidence In vitro kinase assays, Co-IP, phospho-site mutagenesis of MCM7, cell-cycle analysis, xenografts, and transcriptomics

    PMID:38117512

    Open questions at the time
    • How PLCE1 potentiates RIOK2 kinase activity toward MCM7 not mechanistically defined
    • Interplay between the E2F1 and RIOK2 arms unclear
  7. 2025 High

    Identified an upstream brake on PLCE1 catalysis, showing TAK1 phosphorylation at S1060 directly downregulates PIP2 hydrolysis and metastasis signaling.

    Evidence Co-IP/mass spectrometry, in vitro phosphorylation, S1060 phospho-mutagenesis, DAG/IP3 hydrolysis assays, and metastatic xenografts

    PMID:40266671

    Open questions at the time
    • Physiological signals that engage TAK1-PLCE1 regulation not defined
    • Whether S1060 phosphorylation operates in non-cancer tissues unknown
  8. 2016 Medium

    Established post-transcriptional repression of PLCE1 by miRNAs, defining a layer of regulation that constrains its oncogenic output.

    Evidence Dual-luciferase 3'UTR reporter assays for miR-145 and miR-328, mimic/inhibitor transfection, proliferation/invasion assays, rescue, and in vivo metastasis models

    PMID:26657507 PMID:26773497

    Open questions at the time
    • Upstream control of these miRNAs in tumors not characterized
    • In vivo relevance of endogenous miRNA-PLCE1 tuning untested
  9. 2024 Medium

    Extended PLCE1 function beyond cancer and kidney to cardiac injury, fibrosis, immunity, and oncolytic-virus therapy, indicating broad context-dependent roles.

    Evidence Knockdown/knockout in cardiomyocytes (pyroptosis/mitochondrial assays), hepatic stellate cells (Ca2+/IP3 pathway), Mtb-infected macrophages and KO mice, and a CRISPR-Cas9 screen with U-73122 inhibition in vivo

    PMID:38451080 PMID:38499110 PMID:39325099 PMID:41759376

    Open questions at the time
    • Shared molecular mechanism across these contexts not unified
    • Direct effectors in cardiac and immune settings largely undefined

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how PLCE1's lipase catalytic activity versus its direct protein-scaffolding interactions are partitioned across its developmental, oncogenic, and inflammatory roles.
  • No catalytic-dead separation-of-function study spanning podocyte, ESCC, and cardiac roles
  • Structural models of PLCE1-p53/MDM2/p65 complexes lacking
  • Tissue-specific upstream activators of PLCE1 incompletely mapped

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 2 GO:0098772 molecular function regulator activity 2 GO:0140098 catalytic activity, acting on RNA 2 GO:0016787 hydrolase activity 1
Localization
GO:0005886 plasma membrane 2 GO:0005829 cytosol 1
Pathway
R-HSA-1643685 Disease 4 R-HSA-162582 Signal Transduction 3 R-HSA-168256 Immune System 3 R-HSA-1266738 Developmental Biology 2 R-HSA-1640170 Cell Cycle 2 R-HSA-5357801 Programmed Cell Death 2
Partners
CDC42IQGAP1MDM2NCK2RAC1RELATAK1TP53

Evidence

Reading pass · 20 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2006 Positional cloning identified loss-of-function mutations in PLCE1 (phospholipase C epsilon 1) as causing early-onset nephrotic syndrome with diffuse mesangial sclerosis (DMS). Immunofluorescence showed PLCε1 expression in developing and mature glomerular podocytes, and DMS was shown to represent an arrest of normal glomerular development. IQGAP1 (IQ motif-containing GTPase-activating protein 1) was identified as a new interaction partner of PLCε1 by this study. Knockdown of plce1 in zebrafish recapitulated human nephrotic syndrome, establishing a causal role in glomerulogenesis. Positional cloning, immunofluorescence localization, protein interaction (Co-IP/pulldown for IQGAP1), zebrafish knockdown model Nature genetics High 17086182
2020 PLCE1 regulates Rho GTPase activity in podocytes: it interacts with Rac1 and Cdc42 (but not RhoA) through its pleckstrin homology (PH) domain and Ras GTP-binding domains (RA1/RA2). Knockdown or knockout of PLCE1 decreased GTP-bound Rac1 and Cdc42 levels and reduced podocyte migration. PLCE1 also interacted with NCK2 (but not NCK1), and NCK2 knockout similarly reduced podocyte migration. Additionally, PLCE1 knockout reduced EGF-induced ERK activation and cell proliferation, and decreased expression of podocyte differentiation markers (NEPH1, NPHS1, WT1, SYNPO). Knockdown/knockout in podocytes, GTP-bound Rac1/Cdc42 pull-down assay, co-immunoprecipitation (PLCE1-NCK2 interaction), migration assay, ERK phosphorylation assay, differentiation marker expression Experimental & molecular medicine High 32238860
2019 Hypomethylation-associated upregulation of PLCE1 activates NF-κB signaling in ESCC through the PI-PLCε pathway. PLCE1 directly binds p65 and IκBα proteins, promoting phosphorylation of IκBα at S32 and p65 at S536, thereby facilitating nuclear translocation of p50/p65. Nuclear p65 then binds VEGF-C and Bcl-2 promoters, enhancing angiogenesis and inhibiting apoptosis. Promoter hypomethylation of PLCE1 was measured by MALDI-TOF mass spectrometry. Co-immunoprecipitation (PLCE1-p65, PLCE1-IκBα binding), phosphorylation assays, nuclear translocation assays, promoter binding (ChIP), xenograft mouse model, MALDI-TOF mass spectrometry for methylation Molecular cancer High 30609930
2020 Hypomethylation-mediated upregulation of PLCE1 inhibits autophagy and promotes p53 degradation in ESCC. PLCE1 directly binds both p53 and MDM2, promoting MDM2-dependent ubiquitination and degradation of p53 while stabilizing MDM2 (increasing its half-life and inhibiting its ubiquitination). Knockdown of PLCE1 combined with wild-type p53 overexpression increased autophagy and apoptosis in vivo. Co-immunoprecipitation (PLCE1-p53 and PLCE1-MDM2 direct binding), ubiquitination assay, half-life measurement (cycloheximide chase), xenograft mouse model, adenoviral vector rescue experiment Cancer research High 32066565
2017 PLCE1 promotes esophageal cancer invasion and proliferation by maintaining the protein level of Snail, a transcription factor for invasion. CRISPR/Cas9 inactivation of PLCE1 dramatically decreased invasion and proliferation in vitro and reduced tumor size in vivo. Transcriptomic analysis showed that PLCE1-deficient cells had decreased expression of Snail target genes, and rescue with Snail protein partially restored invasion and proliferation in PLCE1-inactivated cells. CRISPR/Cas9 gene inactivation, in vitro invasion/proliferation assays, xenograft mouse model, transcriptomic analysis, Snail rescue experiment, immunohistochemistry Neoplasia (New York, N.Y.) High 28147304
2018 PLCE1 promotes invasion and migration of esophageal cancer cells by activating the PKCα/NF-κB signaling pathway. Knockdown of PLCE1 by siRNA significantly decreased expression of PKCα and NF-κB-related proteins (p50 and p65) and inhibited migration and invasion of Eca109 and EC9706 cells. PLCE1 expression was positively correlated with PKCα and p50 expression. siRNA knockdown, Western blotting, Transwell migration/invasion assay, correlation analysis Yonsei medical journal Medium 30450849
2024 PLCE1 promotes tumor progression in ESCC via two mechanisms involving MCM7: (1) PLCE1 activates PKCα-mediated phosphorylation of E2F1, leading to transcriptional upregulation of MCM7 and miR-106b-5p; miR-106b-5p in turn suppresses autophagy and apoptosis by targeting Beclin-1 and RBL2. (2) PLCE1 potentiates phosphorylation of MCM7 at six threonine residues by the atypical kinase RIOK2, promoting MCM complex assembly, chromatin loading, and cell-cycle progression. Inhibition of PLCE1 or RIOK2 caused G1-S arrest. In vitro kinase assay, co-immunoprecipitation, phospho-site mutagenesis, cell-cycle analysis, in vivo xenograft model, transcriptomic analysis Cancer research High 38117512
2025 TAK1 kinase interacts with PLCE1 and phosphorylates it at serine 1060 (S1060). Phosphorylation at S1060 decreases PLCE1 enzymatic activity (PIP2 hydrolysis), reducing production of DAG and IP3, thereby suppressing PKC/GSK-3β/β-Catenin signaling and expression of cancer metastasis-related genes. TAK1 knockdown promoted ESCC migration and invasion, while TAK1 overexpression had the opposite effect, both in vitro and in vivo. Co-immunoprecipitation, mass spectrometry, in vitro phosphorylation assay, phospho-site mutagenesis (S1060), PIP2 hydrolysis assay (DAG/IP3 measurement), xenograft metastatic mouse model eLife High 40266671
2018 A four-nucleotide intronic insertion variant (rs71031566 [CATTT]) in PLCE1 creates a silencer element that represses PLCE1 transcription via long-range chromatin interaction with the PLCE1 promoter mediated by OCT-2 binding. Overexpression of PLCE1 in ESCC cells suppressed cell growth in vitro and in vivo, suggesting a tumor suppressor role in this context. PLCE1 was found to be downregulated in the majority of ESCC clinical samples. Fine-mapping of GWAS locus, reporter assay, chromatin conformation capture (3C/4C), OCT-2 binding validation, PLCE1 overexpression with cell growth assay in vitro and xenograft in vivo Carcinogenesis Medium 29106514
2014 PLCE1 suppresses p53 expression in esophageal cancer cells. Knockdown of PLCE1 markedly increased p53 expression (~9.26-fold) and increased apoptosis (~13.8-fold) in CP-C cells. The mechanism involved modulation of p53 promoter methylation. siRNA knockdown, RT-PCR, apoptosis assay, p53 promoter methylation analysis Cancer investigation Low 24766303
2019 PLCE1 promotes myocardial ischemia-reperfusion (I/R) injury-induced inflammation via activation of the NF-κB signaling pathway. Overexpression of PLCE1 increased IL-6, TNF-α, IL-1α (and decreased IL-10) and increased phosphorylation of p38, ERK1/2, and NF-κB P65; knockdown had opposite effects. These findings were established in H9c2 H/R cell model and rat myocardial I/R model. Overexpression and knockdown in H9c2 cells, rat I/R model, cytokine ELISA, Western blot for NF-κB/MAPK phosphorylation Bioscience reports Medium 31217261
2014 Silencing PLCE1 by RNAi in EC9706 esophageal cancer cells arrested the cell cycle in G0/G1 phase, increased apoptosis, decreased cyclin D1 expression, and increased caspase-3 expression. siRNA knockdown, flow cytometry, Western blot (cyclin D1, caspase-3) Asian Pacific journal of cancer prevention Low 25041015
2019 PLCE1 inhibits apoptosis of non-small cell lung cancer (NSCLC) cells by promoting PTEN promoter methylation. PLCE1 knockdown increased PTEN expression and reduced PTEN promoter methylation in H1299 cells, and induced cell apoptosis. siRNA knockdown, methylation-specific PCR, flow cytometry, Western blot European review for medical and pharmacological sciences Low 31364122
2024 PLCE1 promotes doxorubicin-induced cardiomyocyte pyroptosis via mitochondrial dysfunction. Deletion of PLCE1 ameliorated mitochondrial dysfunction by suppressing ROS accumulation and restoring mitochondrial membrane potential, reducing GSDME-mediated pyroptosis. In vivo, PLCE1 inhibition reduced pyroptotic cell death and improved cardiac function. In vitro PLCE1 knockdown/knockout (AC16 cardiomyocytes), C57BL/6 mouse model, ROS measurement, mitochondrial membrane potential assay, GSDME/pyroptosis markers, cardiac function assessment Biochemical pharmacology Medium 38499110
2024 PLCE1 regulates calcium signaling in hepatic stellate cells (HSCs) through the PLCE1/IP3/Ca2+ pathway. EGCG inhibited PLCE1 expression and reduced IP3 levels and cytosolic calcium concentration in activated mouse HSCs. Knockdown of PLCE1 decreased free calcium ion concentration and inhibited HSC proliferation and migration. ROS regulated PLCE1 expression by modulating TFEB-mediated nuclear translocation. PLCE1 knockdown in mouse HSCs, calcium ion concentration measurement, IP3 measurement, RNAseq, TFEB nuclear translocation assay, mouse CCl4 liver fibrosis model European journal of nutrition Medium 39325099
2016 miR-145 directly targets the 3'UTR of PLCE1 mRNA to repress its translation, thereby inhibiting ESCC cell proliferation, migration, metastasis, and controlling cytoskeletal dynamics. miR-145 was expressed at low levels in ESCC and was inversely correlated with PLCE1 protein expression. Dual-luciferase reporter assay (3'UTR targeting), miRNA mimic/inhibitor transfection, cell proliferation/migration/invasion assays, in vivo metastasis model Oncotarget Medium 26657507
2016 miR-328 directly targets PLCE1 by binding to target sequences in the 3'UTR of PLCE1, as confirmed by dual-luciferase reporter assay. Overexpression of miR-328 decreased PLCE1 mRNA and protein, inhibited esophageal cancer cell proliferation and invasion, and enhanced apoptosis. PLCE1 overexpression rescued the inhibitory effect of miR-328. Dual-luciferase reporter assay, miRNA overexpression/inhibition, Western blot, cell proliferation/invasion/apoptosis assays, rescue experiment Biochemical and biophysical research communications Medium 26773497
2017 miR-34a directly targets and suppresses PLCE1 expression in ESCC, functioning as a tumor suppressor. miR-34a inhibited proliferation, migration, and EMT phenotype while promoting apoptosis. PLCE1 promoted tumorigenicity in vivo and its expression was negatively correlated with miR-34a profiles. Dual-luciferase reporter assay (implied by direct target statement), gain- and loss-of-function miRNA analysis, in vivo xenograft model Oncotarget Low 29190930
2024 PLCE1 was identified as a key negative regulator of oncolytic virus (OV) antitumor immunity via CRISPR-Cas9 metabolic gene screening. Pharmacological inhibition of PLCE1 with U-73122 enhanced OV infection efficiency and immunogenic cell death in vitro, and in vivo combination therapy remodeled the tumor immune microenvironment, increasing CD8+ T cells and reducing FOXP3+ Treg cells. CRISPR-Cas9 metabolic gene screen, pharmacological inhibition (U-73122), in vitro OV infection assay, in vivo MC38 colorectal cancer mouse model, immune cell phenotyping Biochemical and biophysical research communications Medium 41759376
2024 PLCε1 deficiency in mice resulted in increased susceptibility to Mycobacterium tuberculosis infection with accumulation of lung myeloid cells and reduced antibacterial responses, but PLCε1 was not required for T cell activation or accumulation. In vitro Mtb-infected bone marrow-derived macrophages confirmed an intrinsic role for PLCE1 in macrophage activation. Gene-specific knockout mouse model, Mtb infection, lung myeloid cell phenotyping, in vitro BMDM infection assay Infection and immunity Medium 38451080

Source papers

Stage 0 corpus · 82 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2010 A shared susceptibility locus in PLCE1 at 10q23 for gastric adenocarcinoma and esophageal squamous cell carcinoma. Nature genetics 422 20729852
2006 Positional cloning uncovers mutations in PLCE1 responsible for a nephrotic syndrome variant that may be reversible. Nature genetics 403 17086182
2010 Genome-wide association study of esophageal squamous cell carcinoma in Chinese subjects identifies susceptibility loci at PLCE1 and C20orf54. Nature genetics 352 20729853
2019 Epigenetically upregulated oncoprotein PLCE1 drives esophageal carcinoma angiogenesis and proliferation via activating the PI-PLCε-NF-κB signaling pathway and VEGF-C/ Bcl-2 expression. Molecular cancer 297 30609930
2011 Genome-wide association study identifies susceptibility loci for dengue shock syndrome at MICB and PLCE1. Nature genetics 169 22001756
2007 Mutations in PLCE1 are a major cause of isolated diffuse mesangial sclerosis (IDMS). Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association 98 18065803
2012 Genetic variation in C20orf54, PLCE1 and MUC1 and the risk of upper gastrointestinal cancers in Caucasian populations. European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation (ECP) 65 22805490
2010 Mutational analysis of the PLCE1 gene in steroid resistant nephrotic syndrome. Journal of medical genetics 59 20591883
2012 Replication study of PLCE1 and C20orf54 polymorphism and risk of esophageal cancer in a Chinese population. Molecular biology reports 56 22744421
2011 Putatively functional PLCE1 variants and susceptibility to esophageal squamous cell carcinoma (ESCC): a case-control study in eastern Chinese populations. Annals of surgical oncology 49 22203178
2012 Potentially functional variants of PLCE1 identified by GWASs contribute to gastric adenocarcinoma susceptibility in an eastern Chinese population. PloS one 46 22412849
2011 Association between novel PLCE1 variants identified in published esophageal cancer genome-wide association studies and risk of squamous cell carcinoma of the head and neck. BMC cancer 44 21689432
2016 Targeting oncogenic PLCE1 by miR-145 impairs tumor proliferation and metastasis of esophageal squamous cell carcinoma. Oncotarget 42 26657507
2012 Distinct genetic association at the PLCE1 locus with oesophageal squamous cell carcinoma in the South African population. Carcinogenesis 39 22865593
2020 PLCE1 regulates the migration, proliferation, and differentiation of podocytes. Experimental & molecular medicine 37 32238860
2016 MiR-328 suppresses the survival of esophageal cancer cells by targeting PLCE1. Biochemical and biophysical research communications 36 26773497
2015 Genetic Variation of BCL2 (rs2279115), NEIL2 (rs804270), LTA (rs909253), PSCA (rs2294008) and PLCE1 (rs3765524, rs10509670) Genes and Their Correlation to Gastric Cancer Risk Based on Universal Tagged Arrays and Fe3O4 Magnetic Nanoparticles. Journal of biomedical nanotechnology 36 26554163
2022 Circular RNA PLCE1 promotes epithelial mesenchymal transformation, glycolysis in colorectal cancer and M2 polarization of tumor-associated macrophages. Bioengineered 34 35349390
2013 Overexpression of PLCE1 in Kazakh esophageal squamous cell carcinoma: implications in cancer metastasis and aggressiveness. APMIS : acta pathologica, microbiologica, et immunologica Scandinavica 34 23659763
2019 PLCE1 promotes myocardial ischemia-reperfusion injury in H/R H9c2 cells and I/R rats by promoting inflammation. Bioscience reports 31 31217261
2020 Hypomethylation-Linked Activation of PLCE1 Impedes Autophagy and Promotes Tumorigenesis through MDM2-Mediated Ubiquitination and Destabilization of p53. Cancer research 29 32066565
2013 Heterozygote of PLCE1 rs2274223 increases susceptibility to human papillomavirus infection in patients with esophageal carcinoma among the Kazakh populations. Journal of medical virology 29 24127316
2013 Elevated expression patterns and tight correlation of the PLCE1 and NF-κB signaling in Kazakh patients with esophageal carcinoma. Medical oncology (Northwood, London, England) 29 24307345
2014 A replication study confirms the association of GWAS-identified SNPs at MICB and PLCE1 in Thai patients with dengue shock syndrome. BMC medical genetics 27 24884822
2015 Association between PLCE1 rs2274223 A > G polymorphism and cancer risk: proof from a meta-analysis. Scientific reports 26 25614244
2014 PLCE1 suppresses p53 expression in esophageal cancer cells. Cancer investigation 23 24766303
2013 GWAS-uncovered SNPs in PLCE1 and RFT2 genes are not implicated in Dutch esophageal adenocarcinoma and squamous cell carcinoma etiology. European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation (ECP) 23 23222411
2021 CircPLCE1 facilitates the malignant progression of colorectal cancer by repressing the SRSF2-dependent PLCE1 pre-RNA splicing. Journal of cellular and molecular medicine 22 34173324
2017 PLCE1 Promotes Esophageal Cancer Cell Progression by Maintaining the Transcriptional Activity of Snail. Neoplasia (New York, N.Y.) 22 28147304
2017 MicroRNA-34a functions as a tumor suppressor by directly targeting oncogenic PLCE1 in Kazakh esophageal squamous cell carcinoma. Oncotarget 22 29190930
2014 Association between phospholipase C epsilon gene (PLCE1) polymorphism and colorectal cancer risk in a Chinese population. The Journal of international medical research 20 24496148
2013 PLCE1 rs2274223 A>G polymorphism and cancer risk: a meta-analysis. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 20 23797815
2008 Exclusion of homozygous PLCE1 (NPHS3) mutations in 69 families with idiopathic and hereditary FSGS. Pediatric nephrology (Berlin, Germany) 18 18975016
2015 Common Genetic Variants of PSCA, MUC1 and PLCE1 Genes are not Associated with Colorectal Cancer. Asian Pacific journal of cancer prevention : APJCP 17 26320491
2013 Novel functional variants locus in PLCE1 and susceptibility to esophageal squamous cell carcinoma: based on published genome-wide association studies in a central Chinese population. Cancer epidemiology 17 23688607
2018 PLCE1 Promotes the Invasion and Migration of Esophageal Cancer Cells by Up-Regulating the PKCα/NF-κB Pathway. Yonsei medical journal 16 30450849
2013 PLCE1 polymorphism and upper gastrointestinal cancer risk: a meta-analysis. PloS one 15 23826241
2014 Effects of PLCE1 gene silencing by RNA interference on cell cycling and apoptosis in esophageal carcinoma cells. Asian Pacific journal of cancer prevention : APJCP 14 25041015
2013 Association of potentially functional genetic variants of PLCE1 with gallbladder cancer susceptibility in north Indian population. Journal of gastrointestinal cancer 14 23975622
2014 A multigenic approach to evaluate genetic variants of PLCE1, LXRs, MMPs, TIMP, and CYP genes in gallbladder cancer predisposition. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 13 24863943
2017 PLCE1 polymorphisms and expression combined with serum AFP level predicts survival of HBV-related hepatocellular carcinoma patients after hepatectomy. Oncotarget 10 28418898
2016 Genome-wide association study identified PLCE1- rs2797992 and EGFR- rs6950826 were associated with TP53 expression in the HBV-related hepatocellular carcinoma of Chinese patients in Guangxi. American journal of translational research 10 27186304
2024 Phospholipase PLCE1 Promotes Transcription and Phosphorylation of MCM7 to Drive Tumor Progression in Esophageal Cancer. Cancer research 9 38117512
2021 Independent and opposing associations of dietary phytosterols intake and PLCE1 rs2274223 polymorphisms on esophageal squamous cell carcinoma risk. European journal of nutrition 9 34046701
2017 Two novel polymorphisms in PLCE1 are associated with the susceptibility to esophageal squamous cell carcinoma in Chinese population. Diseases of the esophagus : official journal of the International Society for Diseases of the Esophagus 9 27061010
2016 Genetic Variations in Phospholipase C-epsilon 1 (PLCE1) and Susceptibility to Colorectal Cancer Risk. Biochemical genetics 9 27383248
2014 PLCE1 rs2274223 polymorphism and susceptibility to esophageal cancer: a meta-analysis. Asian Pacific journal of cancer prevention : APJCP 8 25422186
2024 PLCE1 enhances mitochondrial dysfunction to promote GSDME-mediated pyroptosis in doxorubicin-induced cardiotoxicity. Biochemical pharmacology 7 38499110
2019 PLCE1 inhibits apoptosis of non-small cell lung cancer via promoting PTEN methylation. European review for medical and pharmacological sciences 7 31364122
2015 PLCE1 gene in esophageal cancer and interaction with environmental factors. Asian Pacific journal of cancer prevention : APJCP 7 25854357
2008 NPHS3: new clues for understanding idiopathic nephrotic syndrome. Pediatric nephrology (Berlin, Germany) 7 18270750
2021 PLCE1 Polymorphisms Are Associated With Gastric Cancer Risk: The Changes in Protein Spatial Structure May Play a Potential Role. Frontiers in genetics 6 34531897
2019 PLCE1 Polymorphisms and Risk of Esophageal and Gastric Cancer in a Northwestern Chinese Population. BioMed research international 6 30931333
2018 Functional role of PLCE1 intronic insertion variant associated with susceptibility to esophageal squamous cell carcinoma. Carcinogenesis 6 29106514
2016 In silico transcriptional regulation and functional analysis of dengue shock syndrome associated SNPs in PLCE1 and MICB genes. Functional & integrative genomics 6 27038471
2015 The association between phospholipase C epsilon gene (PLCE1) polymorphisms and colorectal cancer risk in a Chinese Han population: a case-control study. International journal of clinical and experimental medicine 6 26770576
2013 Esophageal squamous cell carcinoma and gastric cardia adenocarcinoma shared susceptibility locus in PLCE1: a meta-analysis. PloS one 6 23874915
2021 Identification of a PLCE1‑regulated competing endogenous RNA regulatory network for esophageal squamous cell carcinoma. Oncology reports 5 33650665
2013 [Relationship between rs2274223 and rs3765524 polymorphisms of PLCE1 and risk of esophageal squamous cell carcinoma in a Kazakh Chinese population]. Zhonghua bing li xue za zhi = Chinese journal of pathology 5 24507095
2024 Phospholipase C epsilon-1 (PLCƐ1) mediates macrophage activation and protection against tuberculosis. Infection and immunity 4 38451080
2024 EGCG suppressed activation of hepatic stellate cells by regulating the PLCE1/IP3/Ca2+ pathway. European journal of nutrition 4 39325099
2023 Genetic Association Studies of MICB and PLCE1 with Severity of Dengue in Indonesian and Taiwanese Populations. Diagnostics (Basel, Switzerland) 4 37958261
2018 Single-Nucleotide Polymorphisms in NOD1, RIPK2, MICB, PLCE1, TNF, and IKBKE Genes Associated with Symptomatic Dengue in Children from Colombia. Viral immunology 4 30332343
2022 PLCE1 alleviates lipopolysaccharide-induced acute lung injury by inhibiting PKC and NF-κB signaling pathways. Allergologia et immunopathologia 3 35527658
2020 Genetic variants in GHR and PLCE1 genes are associated with susceptibility to esophageal cancer. Molecular genetics & genomic medicine 3 32869542
2020 The PLCE1 rs2274223 variant is associated with the risk of laryngeal squamous cell carcinoma. International journal of medical sciences 3 33162810
2018 Cyclosporine A responsive congenital nephrotic syndrome with single heterozygous variants in NPHS1, NPHS2, and PLCE1. Pediatric nephrology (Berlin, Germany) 3 29663071
2024 Polymorphisms of TXK and PLCE1 Genes and Their Correlation Analysis with Growth Traits in Ashidan Yaks. Animals : an open access journal from MDPI 2 39682472
2019 An Association and Meta-Analysis of Esophageal Squamous Cell Carcinoma Risk Associated with PLCE1 rs2274223, C20orf54 rs13042395 and RUNX1 rs2014300 Polymorphisms. Pathology oncology research : POR 2 30666517
2019 The Role of p.Ser1105Ser (in NPHS1 Gene) and p.Arg548Leu (in PLCE1 Gene) with Disease Status of Vietnamese Patients with Congenital Nephrotic Syndrome: Benign or Pathogenic? Medicina (Kaunas, Lithuania) 2 31013750
2017 Genetic variants of MICB and PLCE1 and associations with the laboratory features of dengue. BMC infectious diseases 2 28599625
2014 PLCE1 rs2274223 polymorphism contributes to risk of esophageal cancer: evidence based on a meta-analysis. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 2 24737582
2014 Novel functional variants locus in PLCE1 and susceptibility to digestive tract cancer in the Chinese population: a meta-analysis. The International journal of biological markers 2 24874112
2011 Respiratory-chain deficiency presenting as diffuse mesangial sclerosis with NPHS3 mutation. Pediatric nephrology (Berlin, Germany) 2 21365190
2025 TAK1-mediated phosphorylation of PLCE1 represses PIP2 hydrolysis to impede esophageal squamous cancer metastasis. eLife 1 40266671
2024 [Clinical and genetic analysis of a child with Focal segmental glomerulosclerosis due to a novel variant of PLCE1 gene]. Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics 1 39097274
2022 [Association of GSTP1 and PLCE1 gene polymorphisms with primary esophageal cancer]. Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics 1 36317220
2022 Compound Homozygous Rare Mutations in PLCE1 and HPS1 Genes Associated with Autosomal Recessive Retinitis Pigmentosa in Pakistani Families. Iranian journal of public health 1 36743378
2019 The Correlation between Phospholipase C Epsilon (PLCE1) Gene Polymorphisms and Risk of Gastric Adenocarcinoma in Iranian Population. International journal of hematology-oncology and stem cell research 1 31649800
2026 CRISPR-based metabolic screening identifies PLCE1 as a pivotal regulator of oncolytic viral antitumor immunity via tumor immune microenvironment remodeling. Biochemical and biophysical research communications 0 41759376
2025 [PLCE1 mutation-induced end-stage renal disease presenting with massive proteinuria: a family analysis and literature review]. Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics 0 40462432
2017 Comprehensive bioinformation analysis of the miRNA of PLCE1 knockdown in esophageal squamous cell carcinoma. Molecular and cellular biochemistry 0 29238898

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