Affinage

PLCE1

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

Length
2302 aa
Mass
258.7 kDa
Annotated
2026-04-28
85 papers in source corpus 22 papers cited in narrative 22 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PLCE1 encodes phospholipase C epsilon 1, a multifunctional signaling enzyme that hydrolyzes PIP2 to generate DAG and IP3, thereby activating PKC and calcium-dependent signaling cascades across diverse cell types including podocytes, epithelial cells, cardiomyocytes, and macrophages. In podocytes, PLCE1 interacts with Rho GTPases (Rac1, Cdc42) through its PH and RA domains and with the adaptor proteins IQGAP1 and NCK2, sustaining cytoskeletal dynamics, EGF-induced ERK activation, and expression of differentiation markers; loss-of-function mutations cause early-onset nephrotic syndrome with diffuse mesangial sclerosis representing arrested glomerular development (PMID:17086182, PMID:32238860). In esophageal squamous cell carcinoma, PLCE1 promotes tumorigenesis through PKCα-dependent activation of NF-κB (driving VEGF-C and Bcl-2 transcription), stabilization of MDM2 leading to p53 ubiquitination and degradation, maintenance of Snail protein levels to drive EMT, and PKCα–E2F1-dependent transcription and RIOK2-mediated phosphorylation of MCM7 to facilitate DNA replication licensing (PMID:30609930, PMID:32066565, PMID:28147304, PMID:38117512). PLCE1 enzymatic activity is negatively regulated by TAK1-mediated phosphorylation at S1060, which suppresses PIP2 hydrolysis and downstream PKC/GSK-3β/β-catenin signaling to restrain metastasis (PMID:40266671).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 2006 High

    The genetic basis of early-onset nephrotic syndrome was unknown; positional cloning established that PLCE1 loss-of-function mutations cause diffuse mesangial sclerosis by arresting glomerular podocyte development, founding PLCE1 as a renal disease gene and placing it in podocyte biology.

    Evidence Positional cloning in affected families, immunofluorescence localization in podocytes, co-IP identifying IQGAP1 interaction, zebrafish knockdown recapitulating nephropathy

    PMID:17086182

    Open questions at the time
    • Mechanism linking PLCE1 loss to podocyte developmental arrest was undefined
    • Downstream signaling pathways in podocytes not mapped
    • Whether IQGAP1 interaction is functionally required for glomerular development was untested
  2. 2014 Low

    Whether PLCE1 promotes cancer cell survival and proliferation was unclear; knockdown in esophageal cancer cells caused G0/G1 arrest, increased apoptosis, and elevated p53, providing the first evidence that PLCE1 has pro-survival/oncogenic functions and suppresses p53 expression.

    Evidence siRNA knockdown in ESCC cell lines, flow cytometry, Western blot for cyclin D1/caspase-3/p53

    PMID:24766303 PMID:25041015

    Open questions at the time
    • Mechanism of p53 suppression not defined beyond promoter methylation correlation
    • Single-lab siRNA without independent replication or genetic knockout
    • No in vivo validation
  3. 2016 Medium

    Post-transcriptional regulation of PLCE1 was uncharacterized; dual-luciferase assays demonstrated that miR-145 and miR-328 each directly target the PLCE1 3′-UTR to repress its translation, establishing microRNA-mediated control of PLCE1 levels in ESCC.

    Evidence Dual-luciferase 3′-UTR reporter assays, miRNA overexpression/inhibition, PLCE1 rescue experiments in ESCC cell lines

    PMID:26657507 PMID:26773497

    Open questions at the time
    • In vivo relevance of miRNA-PLCE1 axis not confirmed in genetic models
    • Relative contribution of different miRNAs to PLCE1 regulation not quantified
  4. 2017 High

    How PLCE1 drives invasive behavior was mechanistically undefined; CRISPR knockout revealed that PLCE1 stabilizes Snail protein to promote EMT, and separate studies linked PLCE1 to PKCα expression in esophageal epithelium, establishing PKCα as a key downstream effector.

    Evidence CRISPR/Cas9 KO with Snail rescue, transcriptomic analysis, PLCE1-deficient mouse esophageal tissue, xenograft models

    PMID:28147304 PMID:28402280

    Open questions at the time
    • Mechanism by which PLCE1 stabilizes Snail protein not elucidated
    • Whether PKCα mediates Snail stabilization was untested
    • Contribution of catalytic vs. scaffolding function of PLCE1 unknown
  5. 2018 Medium

    A GWAS risk variant at the PLCE1 locus lacked functional annotation; fine-mapping identified an intronic insertion that creates an OCT-2-dependent silencer element repressing PLCE1 transcription through long-range chromatin looping, providing cis-regulatory context for disease association.

    Evidence Reporter assays, chromatin conformation analysis, OCT-2 binding assay, PLCE1 overexpression xenograft

    PMID:29106514

    Open questions at the time
    • Whether this silencer variant accounts for ESCC risk in population-level analyses was not resolved
    • PLCE1 overexpression showed tumor suppressor activity, conflicting with knockdown data showing oncogenic roles
  6. 2019 High

    The NF-κB activation mechanism downstream of PLCE1 was incomplete; direct co-immunoprecipitation showed PLCE1 binds both p65 and IκBα, promoting IκBα-S32 and p65-S536 phosphorylation and nuclear translocation, with ChIP confirming NF-κB occupancy at VEGF-C and Bcl-2 promoters in ESCC.

    Evidence Co-IP, phosphorylation assays, ChIP, xenograft angiogenesis/apoptosis assays

    PMID:30450849 PMID:30609930

    Open questions at the time
    • Whether PLCE1 catalytic activity or scaffolding mediates NF-κB component binding was not distinguished
    • Whether this mechanism operates beyond ESCC was unclear
  7. 2019 Medium

    PLCE1 function in cardiomyocyte inflammation was unexplored; overexpression and knockdown in ischemia-reperfusion models showed PLCE1 activates p38/ERK/NF-κB to drive pro-inflammatory cytokine production, extending its signaling role to cardiac injury.

    Evidence Gain/loss-of-function in H9c2 cells and rat I/R model, phospho-protein blotting, cytokine ELISA

    PMID:31217261

    Open questions at the time
    • Direct binding partners mediating PLCE1 inflammatory signaling in cardiomyocytes not identified
    • Upstream activator of PLCE1 in I/R context unknown
  8. 2020 High

    The mechanism of p53 suppression by PLCE1 was only correlative; direct binding assays showed PLCE1 physically associates with both p53 and MDM2, stabilizes MDM2 by inhibiting its auto-ubiquitination, and promotes MDM2-dependent p53 ubiquitination and degradation, establishing a scaffolding oncogenic mechanism.

    Evidence Co-IP, ubiquitination assays, cycloheximide chase, in vivo xenograft with adenoviral p53

    PMID:32066565

    Open questions at the time
    • Which domain of PLCE1 mediates MDM2 binding not mapped
    • Whether catalytic activity of PLCE1 contributes to MDM2 stabilization not tested
  9. 2020 High

    PLCE1 signaling in podocytes lacked molecular resolution; co-IP and GTPase activity assays demonstrated that PLCE1 binds Rac1/Cdc42 (but not RhoA) via its PH and RA domains and interacts with NCK2, sustaining GTP-loaded Rac1/Cdc42, EGF-ERK signaling, and podocyte differentiation marker expression.

    Evidence Co-IP in podocytes, GTP-Rac1/Cdc42 pulldown, PLCE1 KO migration and ERK phosphorylation assays

    PMID:32238860

    Open questions at the time
    • Whether RA domain-GTPase interaction is direct or bridged by adaptors not resolved
    • Structural basis of domain-selective GTPase binding unknown
    • In vivo podocyte-specific rescue not performed
  10. 2020 Medium

    PLCE1 connection to autophagy regulation was unexplored; depletion in prostate cancer cells activated AMPK/ULK1-dependent autophagy, causing androgen receptor degradation and loss of AR nuclear translocation, revealing an autophagy-suppressive role for PLCE1.

    Evidence siRNA KD, autophagy flux assays, nuclear fractionation for AR, bicalutamide-resistant cell models

    PMID:32879302

    Open questions at the time
    • How PLCE1 suppresses AMPK activity not defined
    • Whether this occurs through catalytic PIP2 hydrolysis or scaffolding unknown
  11. 2021 Medium

    Autoregulation of PLCE1 expression was unknown; circPLCE1, a nuclear circular RNA from the PLCE1 locus, was shown to bind SRSF2 and repress SRSF2-dependent splicing of linear PLCE1 mRNA, establishing a cis-regulatory RNA feedback loop.

    Evidence RNA immunoprecipitation, binding-site mutagenesis, xenograft growth assays in CRC

    PMID:34173324

    Open questions at the time
    • Whether circPLCE1-SRSF2 interaction regulates PLCE1 in non-CRC contexts not tested
    • Stoichiometry and kinetics of circular vs. linear RNA production at PLCE1 locus unknown
  12. 2024 High

    How PLCE1 interfaces with DNA replication machinery was unknown; studies showed PLCE1 drives MCM7 expression via PKCα→E2F1 transcriptional activation and potentiates RIOK2-mediated MCM7 phosphorylation to promote MCM complex chromatin loading and S-phase entry.

    Evidence Phosphorylation assays (PKCα→E2F1, RIOK2→MCM7), CRISPR KO, transcriptomics, xenograft in ESCC

    PMID:38117512

    Open questions at the time
    • Whether PLCE1 directly binds RIOK2 or MCM7 not shown
    • Generalizability beyond ESCC not tested
  13. 2024 Medium

    PLCE1 roles in innate immunity were unexplored; knockout mice showed increased susceptibility to Mycobacterium tuberculosis with impaired macrophage antibacterial responses but normal T cell activation, establishing a macrophage-intrinsic immune function.

    Evidence PLCE1 KO mice infected with Mtb, bone marrow-derived macrophage assays, lung immune cell profiling

    PMID:38451080

    Open questions at the time
    • Which PLCE1-dependent signaling pathway mediates macrophage bactericidal function not identified
    • Whether PLC catalytic activity is required for antibacterial defense not tested
  14. 2024 Medium

    PLCE1 involvement in cardiotoxic pyroptosis was unknown; deletion of PLCE1 ameliorated doxorubicin-induced mitochondrial dysfunction and GSDME-mediated pyroptosis in cardiomyocytes, identifying PLCE1 as a promoter of inflammatory cell death via mitochondrial ROS.

    Evidence PLCE1 KO/KD, ROS and mitochondrial membrane potential assays, GSDME cleavage, doxorubicin mouse model

    PMID:38499110

    Open questions at the time
    • Direct mechanism linking PLCE1 catalytic activity to mitochondrial dysfunction not defined
    • Whether PLCE1-GSDME axis operates in other pyroptotic contexts unknown
  15. 2025 High

    Post-translational regulation of PLCE1 enzymatic activity was uncharacterized; TAK1 was identified as a kinase that phosphorylates PLCE1 at S1060, directly reducing PIP2 hydrolysis and downstream DAG/IP3-PKC-GSK-3β/β-catenin signaling, providing the first defined inhibitory phosphorylation of PLCE1.

    Evidence Co-IP and mass spectrometry, phospho-site mapping (S1060), PIP2 hydrolysis enzymatic assay, xenograft metastasis model

    PMID:40266671

    Open questions at the time
    • Whether additional kinases phosphorylate PLCE1 at other regulatory sites unknown
    • Structural basis for S1060 phosphorylation inhibiting catalytic activity not resolved
    • Whether TAK1-PLCE1 axis operates outside ESCC not tested

Open questions

Synthesis pass · forward-looking unresolved questions
  • A unified structural and domain-level understanding of how PLCE1 integrates its catalytic (PIP2 hydrolysis) and non-catalytic scaffolding functions (MDM2/p53, NF-κB, Snail stabilization) is lacking, and it remains unresolved whether these distinct mechanisms are cell-type-specific or co-occur.
  • No structural model of full-length PLCE1 exists
  • Catalytic vs. scaffolding contributions not genetically separated in any system
  • Context-dependent tumor-suppressive vs. oncogenic roles at the PLCE1 locus remain unreconciled

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008289 lipid binding 2 GO:0016787 hydrolase activity 2 GO:0060090 molecular adaptor activity 2
Localization
GO:0005829 cytosol 2 GO:0005886 plasma membrane 2
Pathway
R-HSA-162582 Signal Transduction 5 R-HSA-1643685 Disease 3 R-HSA-168256 Immune System 3 R-HSA-5357801 Programmed Cell Death 3 R-HSA-1640170 Cell Cycle 2 R-HSA-9612973 Autophagy 2
Partners
CDC42IQGAP1MDM2NCK2RAC1SRSF2TAK1TP53

Evidence

Reading pass · 22 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2006 Positional cloning identified loss-of-function mutations in PLCE1 as causing early-onset nephrotic syndrome with diffuse mesangial sclerosis (DMS); PLCE1 protein was localized by immunofluorescence to developing and mature glomerular podocytes, and DMS was shown to represent an arrest of normal glomerular development. IQGAP1 was identified as a new interaction partner of PLCε1 by co-immunoprecipitation. Zebrafish plce1 knockdown recapitulated the human nephrotic syndrome phenotype. Positional cloning, immunofluorescence localization, co-immunoprecipitation (IQGAP1 interaction), zebrafish knockdown model Nature genetics High 17086182
2020 PLCE1 in podocytes interacts with Rho GTPases (Rac1 and Cdc42 but not RhoA) through its pleckstrin homology domain and Ras GTP-binding domains 1/2; PLCE1 knockout decreased GTP-bound Rac1 and Cdc42 and reduced cell migration. PLCE1 also interacted with NCK2 (but not NCK1), and NCK2 knockout similarly reduced podocyte migration. Knockout of PLCE1 reduced EGF-induced ERK activation and cell proliferation, and decreased expression of podocyte differentiation markers (NEPH1, NPHS1, WT1, SYNPO). Co-immunoprecipitation, PLCE1 knockout, GTPase activity assays (GTP-bound Rac1/Cdc42 measurement), migration assays, ERK phosphorylation assays Experimental & molecular medicine High 32238860
2019 PLCE1 activates NF-κB signaling via the PI-PLCε pathway; PLCE1 binds directly to both p65 and IκBα proteins, promoting IκBα-S32 phosphorylation and p65-S536 phosphorylation, leading to nuclear translocation of p50/p65. Nuclear p65 then binds VEGF-C and Bcl-2 promoters to enhance angiogenesis and inhibit apoptosis in esophageal squamous cell carcinoma. Co-immunoprecipitation (PLCE1-p65, PLCE1-IκBα binding), phosphorylation assays, nuclear translocation assays, ChIP (p65 binding to VEGF-C/Bcl-2 promoters), in vitro and xenograft in vivo assays, promoter methylation analysis Molecular cancer High 30609930
2020 Hypomethylation-mediated upregulation of PLCE1 in ESCC inhibits autophagy and promotes MDM2-dependent ubiquitination and degradation of p53. PLCE1 binds directly to both p53 and MDM2, stabilizes MDM2 (increased its half-life, inhibited its ubiquitination), and promotes MDM2-dependent ubiquitination and subsequent degradation of p53 in vitro. Knockdown of PLCE1 combined with wild-type p53 adenoviral vector increased autophagy and apoptosis in vivo. Co-immunoprecipitation (PLCE1-p53, PLCE1-MDM2 binding), ubiquitination assays, half-life measurement (cycloheximide chase), in vivo xenograft with adenoviral p53, promoter methylation analysis Cancer research High 32066565
2025 TAK1 kinase interacts with PLCE1 and phosphorylates PLCE1 at serine 1060 (S1060), which decreases PLCE1 enzymatic (phospholipase) activity, reducing PIP2 hydrolysis and lowering DAG and IP3 production. This suppresses PKC/GSK-3β/β-Catenin signaling, thereby impeding expression of metastasis-related genes and reducing ESCC migration and invasion. Co-immunoprecipitation, mass spectrometry (TAK1-PLCE1 interaction), phosphorylation site identification (S1060), enzymatic activity assay (PIP2 hydrolysis), in vitro migration/invasion assays, xenograft metastasis mouse model eLife High 40266671
2024 PLCE1 promotes ESCC tumor progression by two mechanisms involving MCM7: (1) PLCE1 activates PKCα-mediated phosphorylation of E2F1, driving transcriptional activation of MCM7 and miR-106b-5p (which suppresses autophagy/apoptosis via 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. In vitro and in vivo functional assays, phosphorylation assays (PKCα→E2F1, RIOK2→MCM7), transcriptomic analysis, CRISPR/Cas9 loss-of-function, xenograft mouse model Cancer research High 38117512
2017 PLCE1 is required to maintain protein levels of the EMT transcription factor Snail in esophageal cancer cells; CRISPR/Cas9 inactivation of PLCE1 dramatically decreased invasion, proliferation, and Snail protein levels, while reintroduction of Snail partially rescued these phenotypes. Transcriptomic analysis confirmed decreased expression of Snail target genes in PLCE1-deficient cells. CRISPR/Cas9 knockout, in vitro invasion/proliferation assays, Snail protein expression (Western blot), transcriptomic analysis, xenograft tumor model, IHC correlation in clinical specimens Neoplasia (New York, N.Y.) High 28147304
2018 PLCE1 promotes invasion and migration of esophageal cancer cells by upregulating PKCα, which in turn activates NF-κB (p50/p65). Knockdown of PLCE1 by siRNA significantly decreased PKCα and NF-κB protein expression and inhibited Transwell migration and invasion of Eca109 and EC9706 cells. siRNA knockdown, Western blotting (PLCE1, PKCα, p50, p65), Transwell migration/invasion assay, correlation analysis Yonsei medical journal Medium 30450849
2019 PLCE1 promotes inflammation in myocardial ischemia-reperfusion injury by activating NF-κB signaling. Overexpression of PLCE1 increased phosphorylation of p38, ERK1/2, and NF-κB p65, and elevated pro-inflammatory cytokines (IL-6, TNF-α, IL-1α) while reducing IL-10. PLCE1 knockdown had the opposite effects in H/R H9c2 cardiomyocyte and rat I/R models. PLCE1 overexpression and knockdown, Western blotting (phospho-p38, phospho-ERK1/2, phospho-NF-κB p65), cytokine measurement (qPCR/ELISA), H/R cell model, rat I/R model Bioscience reports Medium 31217261
2020 PLCε (PLCE1) depletion in prostate cancer cells triggers enhanced autophagic activity via the AMPK/ULK1 pathway, causing autophagy-mediated AR (androgen receptor) protein degradation and inhibition of AR nuclear translocation, thereby reducing AR-driven cell migration/invasion. PLCE1 siRNA knockdown, Western blotting, autophagy assays, nuclear fractionation (AR translocation), migration/invasion assays, bicalutamide-resistant cell models Cell death & disease Medium 32879302
2014 PLCE1 suppresses p53 expression in esophageal cancer cells; knockdown of PLCE1 increased p53 expression 9.26-fold and increased apoptosis 13.8-fold, with the mechanism involving modulation of p53 promoter methylation. PLCE1 siRNA knockdown, p53 expression measurement, apoptosis assay, promoter methylation analysis Cancer investigation Low 24766303
2017 PLCE1 positively correlates with and regulates PRKCA (PKCα) expression in esophageal epithelium; knockdown of PLCE1 in human esophageal cancer cells led to reduction of PRKCA and downstream cytokines, as confirmed in PLCE1-deficient mouse esophageal epithelial tissues. PLCE1 knockdown in cell lines, PLCE1-deficient mouse model, qPCR/IHC for PRKCA and cytokines, NMBA-treated rat model Oncotarget Medium 28402280
2016 miR-145 directly targets the 3'UTR of PLCE1 and represses PLCE1 translation, inhibiting ESCC cell proliferation, migration, metastasis, and cytoskeletal dynamics; miR-145 and PLCE1 are inversely correlated in ESCC tissues. Dual-luciferase 3'UTR reporter assay, miR-145 overexpression and inhibition, Western blotting, cell proliferation/migration/invasion assays Oncotarget Medium 26657507
2016 miR-328 directly targets PLCE1 by binding its 3'UTR (confirmed by dual-luciferase reporter assay); overexpression of miR-328 decreases PLCE1 mRNA and protein, inhibits esophageal cancer cell proliferation and invasion, and promotes apoptosis, while PLCE1 overexpression rescues these effects. Dual-luciferase 3'UTR reporter assay, miR-328 overexpression/inhibition, PLCE1 rescue experiment, Western blotting, proliferation/invasion/apoptosis assays Biochemical and biophysical research communications Medium 26773497
2017 miR-34a directly targets PLCE1 (confirmed by targeting the 3'UTR) and suppresses PLCE1-driven proliferation, migration, EMT, and tumor growth in ESCC; PLCE1 promotes tumorigenicity in vivo, and miR-34a expression is inversely correlated with PLCE1 in ESCC tissues. Dual-luciferase 3'UTR reporter assay (miR-34a→PLCE1), gain/loss-of-function in ESCC cell lines, in vivo xenograft, IHC correlation Oncotarget Medium 29190930
2018 A four-nucleotide insertion (rs71031566[CATTT]) in intron of 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 suppresses cell growth in vitro and in vivo, suggesting a tumor suppressor role. Fine mapping of GWAS locus, silencer reporter assays, chromatin conformation (long-range interaction), OCT-2 binding assay, PLCE1 overexpression in vitro and in vivo (xenograft) Carcinogenesis Medium 29106514
2024 PLCE1 promotes GSDME-mediated pyroptosis in doxorubicin-induced cardiomyocyte toxicity by enhancing mitochondrial dysfunction (increased ROS accumulation, reduced mitochondrial membrane potential). Deletion of PLCE1 ameliorated mitochondrial dysfunction and reduced pyroptotic cell death in vitro and improved cardiac function in vivo. PLCE1 knockout/knockdown, ROS measurement, mitochondrial membrane potential assay, GSDME pyroptosis markers, AC16 cell line model, C57BL/6 mouse model Biochemical pharmacology Medium 38499110
2014 RNAi-mediated silencing of PLCE1 in EC9706 esophageal carcinoma cells arrests the cell cycle in G0/G1 phase, increases apoptosis, decreases cyclin D1, and increases caspase-3 expression, indicating PLCE1 promotes cell cycle progression and survival via these regulators. siRNA knockdown, flow cytometry (cell cycle, apoptosis), Western blotting (cyclin D1, caspase-3) Asian Pacific journal of cancer prevention Low 25041015
2019 PLCE1 inhibits apoptosis in non-small cell lung cancer by promoting PTEN promoter methylation; PLCE1 knockdown increased PTEN expression and reduced PTEN promoter methylation, which promoted apoptosis in NSCLC cells. siRNA knockdown, promoter methylation assay (PTEN), PTEN expression (qRT-PCR/Western blot), flow cytometry (apoptosis) European review for medical and pharmacological sciences Low 31364122
2024 PLCE1 is required for macrophage-mediated antibacterial responses against Mycobacterium tuberculosis infection; PLCE1 knockout mice showed increased susceptibility to Mtb, accumulation of lung myeloid cells, and reduced antibacterial responses, while T cell activation was not affected. Gene-specific knockout mouse model of Mtb infection, in vitro Mtb-infected bone marrow-derived macrophages, lung cell accumulation analysis Infection and immunity Medium 38451080
2024 EGCG inhibits hepatic stellate cell activation by reducing PLCE1 expression and downstream IP3 production, which decreases intracellular calcium ion concentration; PLCE1 knockdown alone reduced free calcium, cell proliferation, and migration. PLCE1 expression in HSCs is regulated by ROS via TFEB nuclear translocation. PLCE1 knockdown, calcium ion measurement, IP3 measurement, transcriptomics sequencing, in vivo CCl4 liver fibrosis mouse model European journal of nutrition Medium 39325099
2021 CircPLCE1 (hsa_circ_0019230), a nuclear circular RNA derived from the PLCE1 locus, directly binds SRSF2 protein and represses SRSF2-dependent splicing of PLCE1 pre-mRNA, reducing linear PLCE1 mRNA production; mutating circPLCE1 binding sites abolished the inhibition of PLCE1 mRNA, and ectopic circPLCE1 expression promoted CRC tumor growth in vivo. RNA fractionation, RNA immunoprecipitation (circPLCE1-SRSF2 binding), binding site mutagenesis, in vivo xenograft, cell proliferation/migration/apoptosis assays Journal of cellular and molecular medicine Medium 34173324

Source papers

Stage 0 corpus · 85 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 421 20729852
2006 Positional cloning uncovers mutations in PLCE1 responsible for a nephrotic syndrome variant that may be reversible. Nature genetics 400 17086182
2010 Genome-wide association study of esophageal squamous cell carcinoma in Chinese subjects identifies susceptibility loci at PLCE1 and C20orf54. Nature genetics 351 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 296 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 58 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 36 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 30 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 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
2013 Heterozygote of PLCE1 rs2274223 increases susceptibility to human papillomavirus infection in patients with esophageal carcinoma among the Kazakh populations. Journal of medical virology 28 24127316
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
2017 Clinical significance of the correlation between PLCE 1 and PRKCA in esophageal inflammation and esophageal carcinoma. Oncotarget 24 28402280
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
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
2021 CircPLCE1 facilitates the malignant progression of colorectal cancer by repressing the SRSF2-dependent PLCE1 pre-RNA splicing. Journal of cellular and molecular medicine 21 34173324
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
2013 PLCɛ and the RASSF family in tumour suppression and other functions. Advances in biological regulation 19 23958207
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
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
2020 PLCɛ maintains the functionality of AR signaling in prostate cancer via an autophagy-dependent mechanism. Cell death & disease 9 32879302
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
2024 Phospholipase PLCE1 Promotes Transcription and Phosphorylation of MCM7 to Drive Tumor Progression in Esophageal Cancer. Cancer research 6 38117512
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
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
2023 Genetic Association Studies of MICB and PLCE1 with Severity of Dengue in Indonesian and Taiwanese Populations. Diagnostics (Basel, Switzerland) 3 37958261
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
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
2020 The PLCE1 rs2274223 variant is associated with the risk of laryngeal squamous cell carcinoma. International journal of medical sciences 2 33162810
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