Affinage

CCNE1

G1/S-specific cyclin-E1 · UniProt P24864

Length
410 aa
Mass
47.1 kDa
Annotated
2026-06-09
100 papers in source corpus 24 papers cited in narrative 25 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CCNE1 encodes cyclin E1, the regulatory partner of CDK2 that drives the G1/S phase transition through RB phosphorylation, and it functions as a potent oncogene when its dosage is increased (PMID:8833152, PMID:40250405). CCNE1 resides in the chromosome 19q12 amplicon and is the critical driver gene within it: amplicon-carrying ovarian cancer cells specifically depend on CCNE1 for proliferation and survival, undergoing G1/S arrest and apoptosis upon its knockdown (PMID:7698009, PMID:8833152, PMID:21103391). Excess cyclin E1 generates a characteristic oncogenic state — incomplete DNA replication, centrosome amplification, aberrant mitotic spindles, chromosome missegregation, and aneuploidy — as shown in inducible mouse and primary cell models linking overexpression directly to genomic instability and tumorigenesis (PMID:27443516, PMID:30878468). Mechanistically, high CCNE1 dosage activates the MMB-FOXM1 mitotic transcriptional program and disrupts CDK1 homeostasis, creating dependencies that underlie multiple synthetic-lethal vulnerabilities: inhibition of PKMYT1 triggers unscheduled CDK1 activation and premature mitosis selectively in CCNE1-overexpressing cells, an effect synergized by ATR inhibition, while WEE1 inhibition perturbs S-phase entry in a CCNE1 copy-number-dependent manner (PMID:35444283, PMID:40169546, PMID:34622231). CCNE1 amplification is also synthetic lethal with BRCA1 loss and ARID1A mutation, and confers a unique requirement for CDK2-mediated homologous-recombination repair of collapsed replication forks and for the mTOR/HR/checkpoint axis (PMID:24218601, PMID:34070839, PMID:37519629, PMID:35732503). Cyclin E1 abundance is tightly controlled post-translationally by FBXW7-mediated ubiquitin-proteasomal degradation, which is blunted by KDM5B-driven FBXW7 repression and by METTL3-dependent m6A stabilization of CCNE1 mRNA, and CCNE1 transcription is activated by YAP1-TEAD4, MNX1, AURKB-mediated H3S10 phosphorylation, and enhancer hijacking through structural genomic rearrangements (PMID:14648662, PMID:35428764, PMID:32039568, PMID:31455378, PMID:30012177, PMID:38713155, PMID:31542774). Beyond its canonical CDK2 partnership, cyclin E1 also physically binds ANLN and stabilizes it by competitively blocking FZR1-mediated ubiquitination, indicating a non-CDK substrate interaction (PMID:40346052).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 1996 Medium

    Establishing where CCNE1 sits in the genome and that it engages cyclin-dependent kinases to drive G1/S entry framed it as both a positional candidate near tumor-associated loci and a core cell-cycle regulator.

    Evidence FISH and chromosomal mapping confirmed by cloning, placing CCNE1 at 19q12-q13

    PMID:7698009 PMID:8833152

    Open questions at the time
    • CDK interaction inferred from cyclin biology rather than directly reconstituted here
    • no functional consequence of the chromosomal location demonstrated yet
  2. 2003 Medium

    Identifying two routes to cyclin E overexpression — CCNE1 amplification and loss of the FBXW7 degron ligase — defined how tumors elevate cyclin E1 transcriptionally/genomically versus post-translationally.

    Evidence FISH, sequencing, LOH analysis and IHC in endometrial carcinoma

    PMID:14648662

    Open questions at the time
    • correlative tumor data, not a controlled perturbation of FBXW7 in defined cells
    • does not establish downstream oncogenic consequence of the overexpression
  3. 2010 High

    Pinpointing CCNE1 as the single essential driver within the 19q12 amplicon converted a broad copy-number event into a specific, druggable dependency.

    Evidence Gene-specific siRNA knockdown with amplicon-dependent viability, cell-cycle and clonogenic readouts in ovarian cancer cells

    PMID:21103391

    Open questions at the time
    • mechanism connecting amplification to dependency not yet resolved
    • did not identify therapeutic vulnerabilities
  4. 2013 High

    Genome-scale screens revealed that CCNE1-amplified cells become dependent on BRCA1/ubiquitin pathway components and on CDK2, explaining the mutual exclusivity of CCNE1 amplification with BRCA1/2 mutation and nominating CDK2 as a downstream target.

    Evidence Genome-wide shRNA synthetic-lethal screens, CDK2 knockdown/inhibitors, and pharmacological validation

    PMID:24004674 PMID:24218601

    Open questions at the time
    • molecular basis of the BRCA1 requirement not fully dissected
    • resistance via CDK2 upregulation/polyploidy limits durability
  5. 2019 High

    Gain-of-function models in fallopian tube cells and inducible mice demonstrated that cyclin E1 overexpression directly causes centrosome amplification, replication defects, chromosome missegregation and tumors, establishing genomic instability as the oncogenic mechanism.

    Evidence Ectopic expression in primary epithelial cells and a doxycycline-inducible Ccne1 transgenic mouse with chromosome and spindle analyses

    PMID:27443516 PMID:30878468

    Open questions at the time
    • molecular trigger linking cyclin E1 to centrosome overduplication not defined
    • tissue specificity of the hepatocyte phenotype unexplained
  6. 2019 Medium

    Mapping multiple upstream inputs — YAP1-TEAD4 transcriptional activation, enhancer hijacking by structural rearrangements, and m6A mRNA stabilization — showed that tumors elevate CCNE1 through diverse amplification-independent mechanisms.

    Evidence Co-IP/luciferase for YAP1-TEAD4; H3K27ac ChIP-seq, WGS, Hi-C/4C and CRISPR for enhancer hijacking; m6A mapping and stability assays for METTL3

    PMID:31455378 PMID:31542774 PMID:32039568

    Open questions at the time
    • relative contribution of each mechanism across tumor types unknown
    • individual studies are single-lab
  7. 2022 High

    Connecting CCNE1 dosage to MMB-FOXM1 program activation and CDK1 homeostasis disruption identified PKMYT1 as a synthetic-lethal target, since unscheduled CDK1 activation forces premature mitosis selectively in CCNE1-high cells.

    Evidence Genome-scale CRISPR synthetic-lethality screen, transcriptional profiling, and selective PKMYT1 inhibitor RP-6306 with in vivo regressions

    PMID:35444283

    Open questions at the time
    • MMB-FOXM1/CDK1 axis supported by transcriptional data, not fully reconstituted
    • biomarkers distinguishing responders incomplete
  8. 2022 Medium

    FBXW7-CCNE1 turnover was shown to be epigenetically tunable: KDM5B demethylates H3K4me3 at the FBXW7 promoter to repress the ligase and thereby stabilize cyclin E1 protein.

    Evidence KDM5B knockdown/overexpression with ChIP for H3K4me3 at FBXW7 and CCNE1 protein/mRNA distinction in Ewing sarcoma

    PMID:35428764

    Open questions at the time
    • single-lab, single-context demonstration
    • generality across other tumor types untested
  9. 2021 Medium

    Defining further context-specific dependencies — ARID1A-mutant synthetic lethality, mTOR/HR/checkpoint reliance, and CCNE1-driven WEE1i/ATRi sensitivity at S-phase entry — broadened the actionable vulnerability landscape of CCNE1-overexpressing tumors.

    Evidence siRNA synthetic-lethal screening, mTOR-inhibitor treatment with RAD51/ATR rescue, and CCNE1 induction with EdU/γH2AX and PDX validation

    PMID:34070839 PMID:34622231 PMID:35732503

    Open questions at the time
    • overlap and hierarchy among these dependencies not resolved
    • several are single-lab findings
  10. 2023 High

    Assigning CDK2 a specific role in homologous-recombination repair of collapsed replication forks in CCNE1-amplified cells explained why CDK2 inhibition synergizes with DNA-damaging agents in this context.

    Evidence CRISPR whole-genome screens with replication-fork-collapse and HR-repair assays plus combination studies

    PMID:37519629

    Open questions at the time
    • whether this CDK2 function is fully independent of its cyclin E1 G1/S role not resolved
  11. 2025 High

    Newer therapeutic strategies — PKMYT1+ATR co-inhibition and a CDK2 PROTAC that co-depletes CDK2 and cyclin E1 — translated the mechanistic dependencies into agents with CCNE1-selective efficacy, including resensitization of palbociclib-adapted cells.

    Evidence Pharmacological combination with CDK1-activation/γH2AX readouts in PDX, and a CDK2 PROTAC degrader with RB-phosphorylation and antiproliferative assays

    PMID:40169546 PMID:40250405

    Open questions at the time
    • clinical durability and resistance mechanisms not established
    • PROTAC data single-lab
  12. 2025 Medium

    Discovery that cyclin E1 physically binds ANLN and protects it from FZR1-mediated ubiquitination revealed a CDK2-independent, substrate-stabilizing activity of cyclin E1.

    Evidence Co-IP, ubiquitination assays, and site-directed mutagenesis of the ANLN ubiquitination site in TNBC

    PMID:40346052

    Open questions at the time
    • structural basis of the CCNE1-ANLN interaction unknown
    • whether CDK2 contributes to this function untested
    • single-lab finding

Open questions

Synthesis pass · forward-looking unresolved questions
  • How cyclin E1 dosage mechanistically couples to centrosome overduplication and replication-stress generation, and which of the many synthetic-lethal dependencies offers the most durable clinical window, remain unresolved.
  • no reconstituted molecular pathway from cyclin E1 to centrosome amplification
  • relative therapeutic priority among PKMYT1, CDK2, WEE1/ATR, mTOR dependencies undefined
  • in vivo resistance mechanisms across modalities not characterized

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 2 GO:0140096 catalytic activity, acting on a protein 1
Localization
GO:0005634 nucleus 2
Pathway
R-HSA-1640170 Cell Cycle 3 R-HSA-1643685 Disease 3 R-HSA-73894 DNA Repair 2
Partners
ANLNCDK2FBXW7RB1
Complex memberships
cyclin E1-CDK2 complex

Evidence

Reading pass · 25 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1995 Human cyclin E (CCNE1) gene maps to chromosome 19q12-->q13 by FISH, placing it near chromosomal regions involved in human tumors. Fluorescence in situ hybridization (FISH) Cytogenetics and cell genetics Medium 7698009 8833152
1996 CCNE1 (cyclin E) localizes to chromosome 19q12 and interacts with cyclin-dependent kinases to facilitate G1/S phase entry. Chromosomal mapping; functional inference from cyclin-CDK biology confirmed by cloning Genomics Medium 8833152
2003 Cyclin E overexpression in endometrial carcinoma is caused by CCNE1 gene amplification and, less frequently, by loss-of-function mutations in hCDC4 (FBXW7), the F-box protein that tags phosphorylated cyclin E for proteasomal degradation; one tumor with hCDC4 mutation also showed LOH at the locus. FISH for CCNE1 amplification; PCR-SSCP-sequencing for hCDC4 mutations; LOH analysis; immunohistochemistry The Journal of pathology Medium 14648662
2010 CCNE1 is the key driver oncogene within the 19q12 amplicon: siRNA knockdown of CCNE1 (but not other genes in the amplicon) caused G1/S arrest, reduced viability, and apoptosis selectively in amplification-carrying ovarian cancer cells, and inhibited clonogenic survival after cisplatin treatment. siRNA knockdown; cell viability assay; flow cytometry (cell cycle/apoptosis); clonogenic survival assay; correlation of amplification with expression in primary tumors PloS one High 21103391
2013 CCNE1 amplification is synthetic lethal with BRCA1 loss: genome-wide shRNA screen identified BRCA1 and ubiquitin pathway members as selectively required in CCNE1-amplified cancer cells, providing a mechanistic explanation for the mutual exclusivity of CCNE1 amplification and BRCA1/2 mutation in high-grade serous ovarian cancer. Genome-wide shRNA synthetic lethal screen; proteasome inhibitor sensitivity assay (bortezomib) Proceedings of the National Academy of Sciences of the United States of America High 24218601
2013 CDK2 is a therapeutic target downstream of CCNE1 amplification: selective sensitivity of CCNE1-amplified ovarian cancer cells to CDK2 knockdown or small-molecule CDK2 inhibitors was demonstrated; resistance emerged via CDK2 upregulation or selection of pre-existing polyploid cells. siRNA knockdown; small-molecule CDK2 inhibitors; FACS; gene expression and copy number analysis; karyotyping of resistant sublines Clinical cancer research High 24004674
2016 Induced expression of cyclin E1 in fallopian tube epithelial cells increased the percentage of cells showing centrosome amplification, directly linking CCNE1 overexpression to centrosome number abnormality. Ectopic expression of cyclin E1 in fallopian tube epithelial cells; centrosome counting Modern pathology Medium 27443516
2019 Cyclin E1 overexpression in mice (doxycycline-inducible Ccne1T model) caused incomplete DNA replication, centrosome amplification, non-perpendicular mitotic spindles, chromosome missegregation, aneuploidy, and polyploidization specifically in hepatocytes, leading to hepatocellular adenomas and HCCs. Doxycycline-inducible transgenic mouse model; MEF and hepatocyte analysis; chromosome counting; spindle angle measurement; tumor burden assessment Gastroenterology High 30878468
2019 YAP1 positively regulates CCNE1 and CCNE2 expression by forming a complex with the transcription factor TEAD4; metformin disrupts this axis via AMPKα-mediated YAP1 inhibition, causing G1 cell cycle arrest in bladder cancer cells. Co-immunoprecipitation; dual-luciferase reporter assay; RNAi knockdown; Western blot; xenograft model; flow cytometry Journal of experimental & clinical cancer research Medium 31455378
2019 Genomic structural variations in gastric cancer cause enhancer hijacking at the CCNE1 locus: diverse distal enhancers are juxtaposed to CCNE1 proximal regions, disrupting TAD boundaries and creating novel TAD interactions, leading to high CCNE1 expression independent of gene amplification. Paired-end H3K27ac ChIP-seq; whole-genome sequencing; CRISPR/Cas9 editing; chromosome conformation capture (4C-seq, Capture-C); Hi-C Gut High 31542774
2020 METTL3, an m6A methyltransferase, stabilizes CCNE1 mRNA by methylating an m6A site in the 3'-UTR of CCNE1 mRNA, promoting colorectal cancer cell proliferation. m6A modification mapping; siRNA knockdown of METTL3; mRNA stability assay; cell proliferation assay; in vivo xenograft Journal of cellular and molecular medicine Medium 32039568
2022 CCNE1 amplification engenders synthetic lethality with PKMYT1 kinase inhibition: increasing CCNE1 dosage activates the MMB-FOXM1 mitotic transcriptional program, disrupting CDK1 homeostasis; PKMYT1 inhibition (RP-6306) causes unscheduled CDK1 activation selectively in CCNE1-overexpressing cells, forcing early mitosis during S-phase and causing DNA damage and cell death. Genome-scale CRISPR-Cas9 synthetic lethality screen; selective PKMYT1 inhibitor (RP-6306) development; cell cycle and DNA synthesis assays; in vivo xenograft regressions; MMB-FOXM1 pathway analysis Nature High 35444283
2022 KDM5B, a histone H3K4 demethylase, promotes CCNE1 protein accumulation in Ewing sarcoma by demethylating H3K4me3 at the FBXW7 promoter, thereby reducing FBXW7 transcription and blocking FBXW7-mediated ubiquitin-proteasomal degradation of CCNE1. KDM5B knockdown/overexpression; Western blot for CCNE1 protein and mRNA; ChIP for H3K4me3 at FBXW7 promoter; in vivo xenograft Cell death & disease Medium 35428764
2023 CDK2, the canonical kinase partner of cyclin E1, uniquely regulates homologous recombination repair of collapsed replication forks in CCNE1-amplified ovarian cancer cells; CDK2 inhibition synergizes with DNA-damaging agents selectively in this genetic context. CRISPR whole-genome screens; CDK2 inhibitor treatment; replication fork collapse assays; HR repair assays; in vitro and in vivo combination studies NAR cancer High 37519629
2025 Combined PKMYT1 inhibition (RP-6306) and ATR inhibition (RP-3500) synergistically increases CDK1 activation, triggers premature mitosis, DNA damage, and apoptosis in a CCNE1-dependent manner, with durable antitumor activity in CCNE1-amplified patient-derived xenografts. Pharmacological combination studies; CDK1 activation assays; DNA damage markers (γH2AX); apoptosis assays; patient-derived xenograft models Nature communications High 40169546
2021 CCNE1 is synthetic lethal with ARID1A mutation in ovarian clear cell carcinoma: siRNA knockdown of CCNE1 selectively reduced proliferation in ARID1A-mutant cell lines but not in ARID1A wild-type lines, confirmed in vivo in xenograft models. siRNA screen for synthetic lethal partners of ARID1A; siRNA knockdown of CCNE1; cell proliferation assay; in vivo xenograft International journal of molecular sciences Medium 34070839
2025 A selective CDK2 PROTAC degrader co-depletes CDK2 and cyclin E1 protein, achieving complete RB phosphorylation suppression and antiproliferative activity with greater selectivity for CCNE1-amplified cells; co-depletion resensitizes palbociclib-adapted breast cancer cells to cell cycle blockade. PROTAC degrader; Western blot for CDK2 and cyclin E1 protein levels; RB phosphorylation assays; antiproliferative assays; palbociclib-resistant cell models; in vivo oral dosing Cell chemical biology Medium 40250405
2025 CCNE1 stabilizes ANLN (Anillin) protein in TNBC by competitively inhibiting FZR1-mediated ubiquitination of ANLN; CCNE1 physically interacts with ANLN, and mutation of the ANLN ubiquitination site abrogates CCNE1's regulatory effect, demonstrating a non-CDK substrate interaction of cyclin E1. Co-immunoprecipitation (CCNE1-ANLN interaction); ubiquitination assays; site-directed mutagenesis of ANLN ubiquitination site; knockdown/overexpression functional assays; in vivo xenograft Cell death discovery Medium 40346052
2024 AURKB promotes CCNE1 expression in colorectal cancer by triggering phosphorylation of histone H3 at serine 10 (pH3S10) in the CCNE1 promoter region, thereby epigenetically activating CCNE1 transcription. ChIP assay for pH3S10 at CCNE1 promoter; AURKB knockdown; Western blot; xenograft model; AURKB inhibitor (AZD1152) Aging Medium 38713155
2021 SENP1-mediated SUMOylation of HIF-1α upregulates STC1 expression, which in turn increases CCNE1 expression and promotes Wilms tumor cell malignancy; SENP1 knockdown inhibits cell viability and CCNE1 levels in vitro and in vivo. Gain- and loss-of-function assays; SUMOylation analysis; Western blot; xenograft tumor model; co-expression analysis Molecular therapy oncolytics Low 34820505
2021 TCF7L2 transcription factor binds to MYLK-AS1 lncRNA and positively promotes CCNE1 transcription; MYLK-AS1 silencing reduces TCF7L2-driven CCNE1 expression, inhibiting nephroblastoma cell proliferation. RNA binding protein immunoprecipitation; ChIP; dual-luciferase reporter assay; gain/loss-of-function; xenograft Journal of cellular physiology Low 33438217
2018 MNX1 transcriptionally upregulates CCNE1 and CCNE2 by directly binding to their promoters, promoting G1-S transition in bladder cancer cells. Chromatin immunoprecipitation (ChIP) to MNX1 binding at CCNE1/CCNE2 promoters; RT-PCR; Western blot; knockdown/overexpression proliferation assays; in vivo xenograft Journal of experimental & clinical cancer research Medium 30012177
2022 CCNE1 overexpression disrupts CDK1 homeostasis at least in part through early activation of the MMB-FOXM1 mitotic transcriptional program, as demonstrated by transcriptional profiling in CCNE1-overexpressing cells. Transcriptional program analysis; CCNE1 dose-dependent gene expression profiling; CRISPR functional screens Nature Medium 35444283
2021 CCNE1 overexpression in CCNE1-amplified tumors leads to increased dependence on the mTOR, homologous recombination, and DNA checkpoint pathways; mTOR inhibitors downregulate HR/checkpoint genes in CCNE1-amplified cells and show selective efficacy, and overexpression of HR/checkpoint proteins (RAD51 or ATR) confers resistance to mTORi. TCGA pathway enrichment analysis; Interactome Mapping Analysis; mTOR inhibitor treatment; Western blot for HR genes; overexpression rescue experiments; in vivo xenograft Molecular cancer therapeutics Medium 35732503
2021 CCNE1 overexpression selectively drives sensitivity to WEE1 inhibition at S-phase entry: only upon CCNE1 induction does WEE1 inhibition perturb DNA synthesis at S-phase entry; adding ATR inhibition increases double-strand breaks during DNA synthesis in a CCNE1 copy-number-dependent manner. CCNE1 induction experiments; DNA synthesis assays (EdU); DSB markers (γH2AX); WEE1i and ATRi combination; patient-derived xenograft models Cell reports. Medicine High 34622231

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2019 The circRNA circAGFG1 acts as a sponge of miR-195-5p to promote triple-negative breast cancer progression through regulating CCNE1 expression. Molecular cancer 271 30621700
2013 Synthetic lethality between CCNE1 amplification and loss of BRCA1. Proceedings of the National Academy of Sciences of the United States of America 190 24218601
2022 CCNE1 amplification is synthetic lethal with PKMYT1 kinase inhibition. Nature 186 35444283
2013 Resistance to CDK2 inhibitors is associated with selection of polyploid cells in CCNE1-amplified ovarian cancer. Clinical cancer research : an official journal of the American Association for Cancer Research 105 24004674
2020 CCNE1 Amplification as a Predictive Biomarker of Chemotherapy Resistance in Epithelial Ovarian Cancer. Diagnostics (Basel, Switzerland) 104 32380689
2018 Biomarker Assessment of HR Deficiency, Tumor BRCA1/2 Mutations, and CCNE1 Copy Number in Ovarian Cancer: Associations with Clinical Outcome Following Platinum Monotherapy. Molecular cancer research : MCR 99 29724815
2020 Methyltransferase like 3 promotes colorectal cancer proliferation by stabilizing CCNE1 mRNA in an m6A-dependent manner. Journal of cellular and molecular medicine 92 32039568
2013 MicroRNA-7 arrests cell cycle in G1 phase by directly targeting CCNE1 in human hepatocellular carcinoma cells. Biochemical and biophysical research communications 91 24370822
2010 Amplicon-dependent CCNE1 expression is critical for clonogenic survival after cisplatin treatment and is correlated with 20q11 gain in ovarian cancer. PloS one 89 21103391
2022 Multicenter Phase II Trial of the WEE1 Inhibitor Adavosertib in Refractory Solid Tumors Harboring CCNE1 Amplification. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 87 36469840
2015 MicroRNA-30c-2-3p negatively regulates NF-κB signaling and cell cycle progression through downregulation of TRADD and CCNE1 in breast cancer. Molecular oncology 82 25732226
2019 Metformin targets a YAP1-TEAD4 complex via AMPKα to regulate CCNE1/2 in bladder cancer cells. Journal of experimental & clinical cancer research : CR 80 31455378
2021 CCNE1 copy number is a biomarker for response to combination WEE1-ATR inhibition in ovarian and endometrial cancer models. Cell reports. Medicine 78 34622231
2020 Exosomal microRNA-144 from bone marrow-derived mesenchymal stem cells inhibits the progression of non-small cell lung cancer by targeting CCNE1 and CCNE2. Stem cell research & therapy 76 32102682
2013 MiR-15a is underexpressed and inhibits the cell cycle by targeting CCNE1 in breast cancer. International journal of oncology 76 23900351
2015 miR-497 and miR-34a retard lung cancer growth by co-inhibiting cyclin E1 (CCNE1). Oncotarget 72 25909221
2016 CCNE1 amplification and centrosome number abnormality in serous tubal intraepithelial carcinoma: further evidence supporting its role as a precursor of ovarian high-grade serous carcinoma. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 69 27443516
1996 Molecular cloning and chromosomal localization of the human cyclin C (CCNC) and cyclin E (CCNE) genes: deletion of the CCNC gene in human tumors. Genomics 62 8833152
2019 Ccne1 Overexpression Causes Chromosome Instability in Liver Cells and Liver Tumor Development in Mice. Gastroenterology 55 30878468
2016 Upregulated expression of BCL2, MCM7, and CCNE1 indicate cisplatin-resistance in the set of two human bladder cancer cell lines: T24 cisplatin sensitive and T24R2 cisplatin resistant bladder cancer cell lines. Investigative and clinical urology 55 26966728
2003 Cyclin E gene (CCNE) amplification and hCDC4 mutations in endometrial carcinoma. The Journal of pathology 55 14648662
1995 Chromosomal mapping of the genes for the human cell cycle proteins cyclin C (CCNC), cyclin E (CCNE), p21 (CDKN1) and KAP (CDKN3). Cytogenetics and cell genetics 54 7698009
2015 CCNE1 amplification is associated with aggressive potential in endometrioid endometrial carcinomas. International journal of oncology 52 26647729
2023 CCNE1 and PLK1 Mediate Resistance to Palbociclib in HR+/HER2- Metastatic Breast Cancer. Clinical cancer research : an official journal of the American Association for Cancer Research 50 36749874
2015 Histo-genomic stratification reveals the frequent amplification/overexpression of CCNE1 and BRD4 genes in non-BRCAness high grade ovarian carcinoma. International journal of cancer 50 25892415
2003 Genome-wide-array-based comparative genomic hybridization reveals genetic homogeneity and frequent copy number increases encompassing CCNE1 in fallopian tube carcinoma. Oncogene 47 12833150
2020 Combined CCNE1 high-level amplification and overexpression is associated with unfavourable outcome in tubo-ovarian high-grade serous carcinoma. The journal of pathology. Clinical research 41 32391646
2019 Integrated paired-end enhancer profiling and whole-genome sequencing reveals recurrent CCNE1 and IGF2 enhancer hijacking in primary gastric adenocarcinoma. Gut 41 31542774
2022 SCUBE3 downregulation modulates hepatocellular carcinoma by inhibiting CCNE1 via TGFβ/PI3K/AKT/GSK3β pathway. Cancer cell international 40 34980127
2022 MEG3 LncRNA from Exosomes Released from Cancer-Associated Fibroblasts Enhances Cisplatin Chemoresistance in SCLC via a MiR-15a-5p/CCNE1 Axis. Yonsei medical journal 39 35184425
2022 CCNE1 and survival of patients with tubo-ovarian high-grade serous carcinoma: An Ovarian Tumor Tissue Analysis consortium study. Cancer 38 36572991
2020 CCNE1 and BRD4 co-amplification in high-grade serous ovarian cancer is associated with poor clinical outcomes. Gynecologic oncology 35 32044108
2017 HOXC13 promotes proliferation of lung adenocarcinoma via modulation of CCND1 and CCNE1. American journal of cancer research 34 28979806
2018 Synthetic lethality in CCNE1-amplified high grade serous ovarian cancer through combined inhibition of Polo-like kinase 1 and microtubule dynamics. Oncotarget 32 29899826
2016 Dual CCNE1/PIK3CA targeting is synergistic in CCNE1-amplified/PIK3CA-mutated uterine serous carcinomas in vitro and in vivo. British journal of cancer 31 27351214
2018 Motor neuron and pancreas homeobox 1/HLXB9 promotes sustained proliferation in bladder cancer by upregulating CCNE1/2. Journal of experimental & clinical cancer research : CR 30 30012177
2017 MicroRNA-874-mediated inhibition of the major G1/S phase cyclin, CCNE1, is lost in osteosarcomas. The Journal of biological chemistry 29 29109143
2022 KDM5B promotes tumorigenesis of Ewing sarcoma via FBXW7/CCNE1 axis. Cell death & disease 28 35428764
2019 Genomic profiling in ovarian cancer retreated with platinum based chemotherapy presented homologous recombination deficiency and copy number imbalances of CCNE1 and RB1 genes. BMC cancer 28 31060523
2019 A novel long non-coding RNA LINC00355 promotes proliferation of lung adenocarcinoma cells by down-regulating miR-195 and up-regulating the expression of CCNE1. Cellular signalling 28 31689506
2016 microRNA-25 Inhibits Cell Apoptosis of Human Gastric Adenocarcinoma Cell Line AGS via Regulating CCNE1 and MYC. Medical science monitor : international medical journal of experimental and clinical research 27 27120728
2014 ALDH maintains the stemness of lung adenoma stem cells by suppressing the Notch/CDK2/CCNE pathway. PloS one 27 24671051
2019 CCNE1 amplification is associated with liver metastasis in gastric carcinoma. Pathology, research and practice 26 31178228
2016 ZYG11A serves as an oncogene in non-small cell lung cancer and influences CCNE1 expression. Oncotarget 26 26771237
2016 Gene amplification of CCNE1, CCND1, and CDK6 in gastric cancers detected by multiplex ligation-dependent probe amplification and fluorescence in situ hybridization. Human pathology 26 27864121
2019 hsa_circ_0062389 promotes the progression of non-small cell lung cancer by sponging miR-103a-3p to mediate CCNE1 expression. Cancer genetics 24 31962276
2023 CDK2 regulates collapsed replication fork repair in CCNE1-amplified ovarian cancer cells via homologous recombination. NAR cancer 22 37519629
2020 Long noncoding RNA LINC01234 silencing exerts an anti-oncogenic effect in esophageal cancer cells through microRNA-193a-5p-mediated CCNE1 downregulation. Cellular oncology (Dordrecht, Netherlands) 22 32130660
2025 Targeting CCNE1 amplified ovarian and endometrial cancers by combined inhibition of PKMYT1 and ATR. Nature communications 21 40169546
2022 Targeting Therapeutic Resistance and Multinucleate Giant Cells in CCNE1-Amplified HR-Proficient Ovarian Cancer. Molecular cancer therapeutics 21 35732503
2014 Characterization of the 19q12 amplification including CCNE1 and URI in different epithelial ovarian cancer subtypes. Experimental and molecular pathology 21 25527175
2025 Profiling the Activity of the Potent and Highly Selective CDK2 Inhibitor BLU-222 Reveals Determinants of Response in CCNE1-Aberrant Ovarian and Endometrial Tumors. Cancer research 20 39945650
2022 Clinical characteristics and outcomes of phase I cancer patients with CCNE1 amplification: MD Anderson experiences. Scientific reports 20 35610322
2016 Chicken gga-miR-103-3p Targets CCNE1 and TFDP2 and Inhibits MDCC-MSB1 Cell Migration. G3 (Bethesda, Md.) 20 26935418
2020 E6 hijacks KDM5C/lnc_000231/miR-497-5p/CCNE1 axis to promote cervical cancer progression. Journal of cellular and molecular medicine 19 32818316
2009 Identification of the gene encoding cyclin E1 (CCNE1) as a novel IGH translocation partner in t(14;19)(q32;q12) in diffuse large B-cell lymphoma. Haematologica 19 19454496
2019 Boosting the apoptotic response of high-grade serous ovarian cancers with CCNE1 amplification to paclitaxel in vitro by targeting APC/C and the pro-survival protein MCL-1. International journal of cancer 18 31286496
2021 Long Non-coding RNA SENP3-EIF4A1 Functions as a Sponge of miR-195-5p to Drive Triple-Negative Breast Cancer Progress by Overexpressing CCNE1. Frontiers in cell and developmental biology 17 33791304
2019 Down-regulation of CCNE1 expression suppresses cell proliferation and sensitizes gastric carcinoma cells to Cisplatin. Bioscience reports 17 31072916
2024 Uncovering the predictive and immunomodulatory potential of transient receptor potential melastatin family-related CCNE1 in pan-cancer. Molecular cancer 16 39551726
2020 CircDENND2A Promotes Non-small Cell Lung Cancer Progression via Regulating MiR-34a/CCNE1 Signaling. Frontiers in genetics 16 33033491
2020 Long non-coding RNA MCF2L-AS1 promotes the aggressiveness of colorectal cancer by sponging miR-874-3p and thereby up-regulating CCNE1. The journal of gene medicine 16 33037865
2019 Dysregulation of long non-coding RNA SNHG12 alters the viability, apoptosis, and autophagy of prostate cancer cells by regulating miR-195/CCNE1 axis. International journal of clinical and experimental pathology 16 31933941
2017 Detection of CCNE1/URI (19q12) amplification by in situ hybridisation is common in high grade and type II endometrial cancer. Oncotarget 16 27582547
2012 Association of germline variation in CCNE1 and CDK2 with breast cancer risk, progression and survival among Chinese Han women. PloS one 16 23185313
2020 Long Noncoding RNA RAET1K Enhances CCNE1 Expression and Cell Cycle Arrest of Lung Adenocarcinoma Cell by Sponging miRNA-135a-5p. Frontiers in genetics 15 32010197
2023 CCNE1 is a predictive and immunotherapeutic indicator in various cancers including UCEC: a pan-cancer analysis. Hereditas 14 36964635
2021 Silencing of long noncoding RNA MYLK-AS1 suppresses nephroblastoma via down-regulation of CCNE1 through transcription factor TCF7L2. Journal of cellular physiology 14 33438217
2017 CCNE1 expression in high grade serous carcinoma does not correlate with chemoresistance. Oncotarget 14 28977941
2015 mTOR is involved in 17β-estradiol-induced, cultured immature boar Sertoli cell proliferation via regulating the expression of SKP2, CCND1, and CCNE1. Molecular reproduction and development 14 25739982
2022 Carbapenemase-Encoding Gene Copy Number Estimator (CCNE): a Tool for Carbapenemase Gene Copy Number Estimation. Microbiology spectrum 13 35863018
2025 CDK2 heterobifunctional degraders co-degrade CDK2 and cyclin E resulting in efficacy in CCNE1-amplified and overexpressed cancers. Cell chemical biology 12 40250405
2024 Structure-Based Drug Design of 2-Amino-[1,1'-biphenyl]-3-carboxamide Derivatives as Selective PKMYT1 Inhibitors for the Treatment of CCNE1-Amplified Breast Cancer. Journal of medicinal chemistry 12 39163619
2021 Ectopic expression of microRNA-874 represses epithelial mesenchymal transition through the NF-κB pathway via CCNE1 in cholangiocarcinoma. Cellular signalling 11 33476715
2021 Multiple bronchiolar adenomas with malignant transformation and CCNE1 mutation: a case report and literature review. Journal of cardiothoracic surgery 11 34663408
2021 Knockdown of SENP1 inhibits HIF-1α SUMOylation and suppresses oncogenic CCNE1 in Wilms tumor. Molecular therapy oncolytics 11 34820505
2013 Genetic polymorphisms in AURKA, BRCA1, CCNE1 and CDK2 are associated with ovarian cancer susceptibility among Chinese Han women. Cancer epidemiology 11 23787073
2024 AURKB promotes colorectal cancer progression by triggering the phosphorylation of histone H3 at serine 10 to activate CCNE1 expression. Aging 10 38713155
2024 CHK1 inhibitor SRA737 is active in PARP inhibitor resistant and CCNE1 amplified ovarian cancer. iScience 10 39021796
2021 CCNE1 Is a Putative Therapeutic Target for ARID1A-Mutated Ovarian Clear Cell Carcinoma. International journal of molecular sciences 10 34070839
2024 Molecular Landscape and Clinical Implication of CCNE1-amplified Esophagogastric Cancer. Cancer research communications 9 38717153
2021 miR‑497/MIR497HG inhibits glioma cell proliferation by targeting CCNE1 and the miR‑588/TUSC1 axis. Oncology reports 9 34664678
2022 Hoxa5 inhibits adipocyte proliferation through transcriptional regulation of Ccne1 and blocking JAK2/STAT3 signaling pathway in mice. Biochemistry and cell biology = Biochimie et biologie cellulaire 7 35623098
2020 Genomic Profiling Comparison of Germline BRCA and Non-BRCA Carriers Reveals CCNE1 Amplification as a Risk Factor for Non-BRCA Carriers in Patients With Triple-Negative Breast Cancer. Frontiers in oncology 7 33194720
2019 MiR-15b regulates cell differentiation and survival by targeting CCNE1 in APL cell lines. Cellular signalling 7 30965092
2023 Circular RNA circSEMA5A facilitates colorectal cancer development by regulating microRNA-195-5p to target CCNE1 axis. Cellular signalling 6 37164546
2022 LncRNA OXCT1-AS1 promotes the proliferation of non-small cell lung cancer cells by targeting the miR-195/CCNE1 axis. Translational cancer research 6 35706791
2022 CCNE1 is a potential target of Metformin for tumor suppression of ovarian high-grade serous carcinoma. Cell cycle (Georgetown, Tex.) 6 36004387
2024 Copy number signatures and CCNE1 amplification reveal the involvement of replication stress in high-grade endometrial tumors oncogenesis. Cellular oncology (Dordrecht, Netherlands) 5 38564163
2024 CircROR1 upregulates CCNE1 expression to promote melanoma invasion and metastasis by recruiting KAT2A. Experimental dermatology 5 38566477
2023 Long Non-coding RNA LINC00473 Promotes Breast Cancer Progression via miR-424-5p/CCNE1 Pathway. Protein and peptide letters 5 36305147
2022 Role of Genetic Variations in CDK2, CCNE1 and p27 in Prostate Cancer. Cancer genomics & proteomics 5 35430569
2021 CCNE1 amplification among metastatic sites in patients with gynecologic high-grade serous carcinoma. Gynecologic oncology reports 5 34485660
2021 CCNE1 and E2F1 Partially Suppress G1 Phase Arrest Caused by Spliceostatin A Treatment. International journal of molecular sciences 5 34769053
2019 CDKN2A, CDK1, and CCNE1 overexpression in sebaceous gland carcinoma of eyelid. International ophthalmology 5 31571090
2025 CCNE1 stabilizes ANLN by counteracting FZR1-mediated the ubiquitination modification to promotes triple negative breast cancer cell stemness and progression. Cell death discovery 4 40346052
2025 Genomic instability and CCNE1 amplification as emerging biomarkers for stratifying high-grade serous ovarian cancer. Frontiers in oncology 4 40842600
2023 PKMYT1: A Potential Target for CCNE1 Amplificated Colorectal Tumors. Cell biochemistry and biophysics 4 37572218
2014 Association of genetic polymorphisms in AURKA, BRCA1, CCNE1 and CDK2 with the risk of endometrial carcinoma and clinicopathological parameters among Chinese Han women. European journal of obstetrics, gynecology, and reproductive biology 4 25463638
2024 Targeting CCNE1 amplified ovarian and endometrial cancers by combined inhibition of PKMYT1 and ATR. Research square 3 38410486

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