Affinage

CCNG1

Cyclin-G1 · UniProt P51959

Length
295 aa
Mass
34.1 kDa
Annotated
2026-06-09
27 papers in source corpus 14 papers cited in narrative 14 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 5/5 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CCNG1 (Cyclin G1) is a conserved p53 transcriptional target that operates within a feedback circuit controlling p53 stability and p53-dependent cell cycle arrest (PMID:40487439). Functionally, CCNG1 acts as a negative regulator of p53 by promoting its degradation: CCNG1 expression is negatively correlated with MDM2, and CCNG1 silencing relieves apoptosis and proliferation defects through the MDM2/p53 axis (PMID:32016904), with elevated CCNG1 driving TP53 degradation to increase irradiation-induced apoptosis (PMID:26623719, PMID:41783157). CCNG1 transcription is induced downstream of Kupffer cell-derived IL-6/JAK/STAT3 signaling, with phospho-STAT3 binding directly to the Ccng1 promoter (PMID:41783157), and is epigenetically repressed by a PRMT6–PRMT5 complex that deposits H3R2me2a alongside PRMT5-mediated H4R3me2s and H3R8me2s marks at the CCNG1 promoter (PMID:36400182). CCNG1 is further positioned downstream of mutant-p53/Notch3 and Wnt/β-catenin signaling, where it contributes to EMT, cisplatin resistance, and radioresistance with G2/M arrest in cancer cells (PMID:30565428, PMID:39511268). Post-transcriptionally, CCNG1 is suppressed by numerous miRNAs targeting its 3'-UTR, the depletion of which restores p53 activity and induces cell cycle arrest, while CCNG1 re-expression rescues these effects (PMID:30119241, PMID:32256207, PMID:33760168).

Mechanistic history

Synthesis pass · year-by-year structured walk · 8 steps
  1. 2016 Medium

    Established that CCNG1 acts as a negative regulator of p53 and sits within a miRNA-controlled feedback loop, framing it as a node linking post-transcriptional control to p53 activity.

    Evidence 3'-UTR luciferase reporter, ectopic miR-27b expression in vitro and in vivo, and epistasis analysis in gastric cancer

    PMID:26623719

    Open questions at the time
    • No direct biochemical reconstitution of a CCNG1–p53 interaction
    • Mechanism by which CCNG1 destabilizes p53 not resolved
  2. 2018 Medium

    Placed CCNG1 downstream of oncogenic signaling axes (mutant-p53/Notch3) driving EMT and chemoresistance, broadening its role beyond a simple p53 target.

    Evidence Overexpression/knockdown, in vivo metastasis assay, and IHC correlation in high-grade serous ovarian cancer

    PMID:30565428

    Open questions at the time
    • No direct interaction assay linking p53mt to the Notch3 promoter
    • Direct CCNG1 effectors downstream of Notch3 unknown
  3. 2018 Medium

    Demonstrated that multiple miRNAs directly target the CCNG1 3'-UTR to control cell cycle and proliferation, with rescue confirming CCNG1 as the functional effector.

    Evidence Luciferase reporter assays, miRNA mimics, flow cytometry, and rescue experiments in ESCC, osteosarcoma, and lung carcinoma (miR-516b, miR-27a, miR-23b)

    PMID:29399167 PMID:30119241 PMID:30214567

    Open questions at the time
    • Downstream mechanism by which CCNG1 controls G1 arrest not biochemically defined
    • Several reports limited to single-lab luciferase validation
  4. 2020 Medium

    Tied CCNG1 mechanistically to the MDM2/p53 pathway, showing CCNG1 suppresses MDM2-dependent p53 control to regulate apoptosis and proliferation.

    Evidence siRNA knockdown and overexpression in podocytes with western blot for MDM2, p53, Bcl-2, Bax

    PMID:32016904

    Open questions at the time
    • No direct binding assay between CCNG1 and MDM2 or p53
    • Mechanism of MDM2 suppression unresolved
  5. 2020 Medium

    Extended CCNG1's reach to EMT, glycolysis, and drug resistance as the shared 3'-UTR endpoint of competing-endogenous-RNA (lncRNA–miRNA) networks.

    Evidence Dual-luciferase, RIP, RNA pull-down, rescue, and xenografts across PDAC, ovarian, and HCC models (miR-122-5p, miR-128-3p/OIP5-AS1, miR-488, miR-130a-5p/FAM225A)

    PMID:32256207 PMID:32271408 PMID:33245102 PMID:33760168

    Open questions at the time
    • Several axes rest on single-lab evidence
    • Direct CCNG1 molecular activity driving EMT/glycolysis not defined
  6. 2022 High

    Defined an epigenetic mechanism controlling CCNG1 transcription, identifying a PRMT6–PRMT5 complex that represses the CCNG1 promoter via arginine methylation marks.

    Evidence Reciprocal Co-IP, GST pulldown, ChIP at the CCNG1 promoter, mass spectrometry, and RNA-seq in colorectal cancer cells

    PMID:36400182

    Open questions at the time
    • Functional consequence of CCNG1 derepression on tumor phenotype not fully traced
    • Recruitment of the PRMT6–PRMT5 complex to the CCNG1 promoter undefined
  7. 2025 Medium

    Validated CCNG1 as an evolutionarily conserved p53 target required for cell cycle arrest independently of p21, anchoring its core physiological role.

    Evidence CRISPR-Cas9 G0 crispant screen in mdm2/puma/noxa/p21 quadruple-knockout zebrafish with cross-species conserved p53-target analysis

    PMID:40487439

    Open questions at the time
    • Molecular mechanism of CCNG1-driven arrest not resolved
    • Relevant CDK/cyclin partners in this context unidentified
  8. 2026 Medium

    Connected upstream cytokine signaling to CCNG1 transcription, showing IL-6/JAK/STAT3 drives Ccng1 expression to promote p53 degradation and radiation-induced apoptosis.

    Evidence ChIP for p-STAT3 binding to the Ccng1 promoter, scRNA-seq, siRNA knockdown with phenotypic rescue, and anti-IL-6 intervention in vivo

    PMID:41783157

    Open questions at the time
    • Direct mechanism by which CCNG1 promotes TP53 degradation still inferred, not biochemically shown
    • Single-lab evidence

Open questions

Synthesis pass · forward-looking unresolved questions
  • The direct biochemical mechanism by which CCNG1 destabilizes p53 (its physical partners, enzymatic complex, and CDK association) remains undefined.
  • No structural or biochemical model of CCNG1 action
  • Partner kinase/phosphatase identity unestablished in this corpus
  • Direct substrate or scaffold function not demonstrated

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 3
Pathway
R-HSA-162582 Signal Transduction 3 R-HSA-1640170 Cell Cycle 3 R-HSA-4839726 Chromatin organization 1
Partners
MDM2TP53

Evidence

Reading pass · 14 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2016 CCNG1 functions as a negative regulator of P53 stability; miR-27b directly targets the 3'-UTR of CCNG1, leading to increased P53 activity which in turn directly regulates miR-508-5p expression, establishing a miR-27b/CCNG1/P53/miR-508-5p axis in multidrug resistance of gastric cancer. 3'-UTR luciferase reporter assay, ectopic miR-27b expression in vitro and in vivo, epistasis analysis of CCNG1/P53/miR-508-5p pathway Oncotarget Medium 26623719
2018 Mutant P53 (P53mt) increases CCNG1 expression by upregulating Notch3; a positive correlation between CCNG1 and Notch3 protein expression was confirmed, placing CCNG1 downstream of a P53mt-Notch3 axis that promotes tumor progression in high-grade serous ovarian cancer. In vitro overexpression/knockdown, in vivo metastasis assay, IHC correlation analysis, EMT and cisplatin resistance assays Cancer medicine Medium 30565428
2020 CCNG1 silencing in podocytes (MPC-5 cells) under high-glucose conditions reverses proliferation inhibition and apoptosis induction via the MDM2/p53 signaling pathway; CCNG1 expression was negatively correlated with MDM2 levels, suggesting CCNG1 promotes p53 activity by suppressing MDM2. siRNA knockdown and overexpression in MPC-5 cells, CCK-8, flow cytometry, RT-qPCR and western blot for MDM2, p53, Bcl-2, Bax International urology and nephrology Medium 32016904
2022 PRMT6 interacts with PRMT5 and deposits H3R2me2a at the CCNG1 promoter, coinciding with PRMT5-mediated H4R3me2s and H3R8me2s marks, leading to transcriptional repression of CCNG1 in colorectal cancer cells. Co-immunoprecipitation, GST pulldown, ChIP, RNA-seq, western blot, mass spectrometry for PRMT6 interaction partners Experimental cell research High 36400182
2025 ccng1 (zebrafish ortholog) contributes to p53-dependent cell cycle arrest; identified via CRISPR-Cas9 crispant screen in mdm2/puma/noxa/p21 quadruple knockout zebrafish as a conserved p53 transcriptional target required for cell cycle arrest independently of p21. CRISPR-Cas9 G0 crispant screen in zebrafish, cross-species conserved p53-upregulated gene analysis, genetic epistasis in quadruple KO background iScience Medium 40487439
2024 CCNG1 functions as a downstream effector of the Wnt/β-catenin signaling pathway in esophageal squamous cell carcinoma; CCNG1 knockdown increased radiosensitivity, enhanced G2/M phase arrest and apoptosis following radiation, and western blot confirmed CCNG1 is regulated by Wnt/β-catenin. Radioresistant ESCC cell line generation, siRNA knockdown, flow cytometry (cell cycle and apoptosis), western blot for Wnt/β-catenin components, bulk and single-cell RNA-seq Scientific reports Medium 39511268
2026 Kupffer cell-derived IL-6 activates hepatocyte STAT3 through classical JAK-STAT signaling; activated phospho-STAT3 binds the promoter of the Ccng1 gene (confirmed by ChIP), increasing Ccng1 transcription; elevated CCNG1 then promotes TP53 degradation, increasing hepatocyte apoptosis after irradiation. ChIP assay (p-STAT3 binding to Ccng1 promoter), scRNA-seq, flow cytometry, siRNA Ccng1 knockdown, IL-6 treatment, anti-IL-6 intervention in vivo Advances in radiation oncology Medium 41783157
2018 miR-516b directly targets CCNG1 (confirmed by luciferase reporter assay of 3'-UTR), and its upregulation induces G1 cell cycle arrest and apoptosis in esophageal squamous cell carcinoma cells, with CCNG1 overexpression rescuing miR-516b effects. Luciferase reporter assay, miR-516b mimics transfection, flow cytometry (cell cycle), apoptosis assays, xenograft model Biomedicine & pharmacotherapy Medium 30119241
2018 miR-27a directly targets CCNG1 (confirmed by luciferase reporter assay) and suppresses CCNG1 protein expression in osteosarcoma cells, functioning as an oncogene by downregulating this tumor suppressor target. Luciferase reporter assay, western blot, RT-qPCR, Transwell invasion/migration assays Oncology letters Low 29399167
2018 CCNG1 is directly targeted by miR-23b (confirmed by luciferase reporter assay of CCNG1 3'-UTR); miR-23b overexpression suppresses CCNG1 protein and inhibits lung carcinoma cell proliferation; CCNG1 interference partially reverses the anti-proliferative effect of miR-23b. Luciferase reporter assay, MTT proliferation assay, Transwell assay, western blot Oncology letters Low 30214567
2020 CCNG1 is a direct target of miR-122-5p (confirmed by dual luciferase reporter assay); overexpression of miR-122-5p suppresses CCNG1 and inhibits EMT, proliferation, migration, and invasion in pancreatic ductal adenocarcinoma; CCNG1 overexpression partially reverses these effects. Dual luciferase reporter assay, MTT, colony formation, flow cytometry, Transwell assay, xenograft model, western blot Cancer cell international Medium 32256207
2021 miR-128-3p directly targets CCNG1 (confirmed by dual-luciferase reporter assay, RNA immunoprecipitation, and RNA pull-down); the lncRNA OIP5-AS1 sequesters miR-128-3p to upregulate CCNG1, promoting ovarian cancer cell viability, migration, invasion, and glycolysis. Dual-luciferase reporter assay, RNA immunoprecipitation (RIP), RNA pull-down, siRNA knockdown, in vivo tumor xenograft, western blot, flow cytometry Molecular medicine reports Medium 33760168
2020 miR-488 directly targets CCNG1 (confirmed by dual-luciferase reporter assay); miR-488 inhibits ovarian cancer cell metastasis by blocking EMT and promoting p53 expression through suppression of CCNG1; CCNG1 overexpression impairs miR-488 inhibitory effects. Dual-luciferase reporter assay, Transwell assay, EMT marker western blot, qRT-PCR European review for medical and pharmacological sciences Low 32271408
2020 miR-130a-5p directly targets the 3'-UTR of CCNG1 to negatively regulate its expression; in hepatocellular carcinoma, lncRNA FAM225A sequesters miR-130a-5p to upregulate CCNG1 and confer sorafenib resistance; CCNG1 overexpression partially offsets FAM225A knockdown-induced re-sensitization to sorafenib. Dual interaction assay (luciferase implied), MTT assay, xenograft model, siRNA knockdown, CCNG1 overexpression rescue Bioscience reports Low 33245102

Source papers

Stage 0 corpus · 27 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2016 The miR27b-CCNG1-P53-miR-508-5p axis regulates multidrug resistance of gastric cancer. Oncotarget 67 26623719
2018 The C/EBPβ-LINC01133 axis promotes cell proliferation in pancreatic ductal adenocarcinoma through upregulation of CCNG1. Cancer letters 52 29458145
2020 MicroRNA-122-5p inhibits cell proliferation, migration and invasion by targeting CCNG1 in pancreatic ductal adenocarcinoma. Cancer cell international 35 32256207
2018 CCNG1 (Cyclin G1) regulation by mutant-P53 via induction of Notch3 expression promotes high-grade serous ovarian cancer (HGSOC) tumorigenesis and progression. Cancer medicine 30 30565428
2018 MicroRNA-23b and microRNA-27b plus flutamide treatment enhances apoptosis rate and decreases CCNG1 expression in a castration-resistant prostate cancer cell line. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 25 30400755
2018 miR-516b functions as a tumor suppressor by directly modulating CCNG1 expression in esophageal squamous cell carcinoma. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 21 30119241
2019 lncRNA LINC01494 Promotes Proliferation, Migration And Invasion In Glioma Through miR-122-5p/CCNG1 Axis. OncoTargets and therapy 17 31571916
2021 Long non‑coding RNA OIP5‑AS1 facilitates the progression of ovarian cancer via the miR‑128‑3p/CCNG1 axis. Molecular medicine reports 16 33760168
2022 PRMT6 functionally associates with PRMT5 to promote colorectal cancer progression through epigenetically repressing the expression of CDKN2B and CCNG1. Experimental cell research 14 36400182
2020 MicroRNA-488 inhibits ovarian cancer cell metastasis through regulating CCNG1 and p53 expression. European review for medical and pharmacological sciences 14 32271408
2018 miR-23b suppresses lung carcinoma cell proliferation through CCNG1. Oncology letters 13 30214567
2020 Silencing CCNG1 protects MPC-5 cells from high glucose-induced proliferation-inhibition and apoptosis-promotion via MDM2/p53 signaling pathway. International urology and nephrology 12 32016904
2017 MicroRNA-27a functions as an oncogene in human osteosarcoma by targeting CCNG1. Oncology letters 11 29399167
2020 FAM225A promotes sorafenib resistance in hepatocarcinoma cells through modulating miR-130a-5p-CCNG1 interaction network. Bioscience reports 9 33245102
2020 The stimulative function of long noncoding RNA CDKN2B-AS1 in osteosarcoma by targeting the microRNA-122/CCNG1 axis. Journal of receptor and signal transduction research 6 33283575
2023 Abnormal expression of miRNA-122 in cerebral infarction and related mechanism of regulating vascular endothelial cell proliferation and apoptosis by targeting CCNG1. Clinics (Sao Paulo, Brazil) 5 37119591
2025 p21, ccng1, foxo3b, and fbxw7 contribute to p53-dependent cell cycle arrest. iScience 4 40487439
2022 lncRNA MSC-AS1 Aggravates Diabetic Nephropathy by Regulating the miR-325/CCNG1 Axis. Journal of healthcare engineering 4 35126911
2022 Differential expression of cyclins CCNB1 and CCNG1 is involved in the chondrocyte damage of kashin-beck disease. Frontiers in genetics 3 36588792
2024 Implication of CCNG1 in radiosensitivity via the Wnt/β-catenin pathway in esophageal squamous cells. Scientific reports 2 39511268
2024 DeltaRex-G, tumor targeted retrovector encoding a CCNG1 inhibitor, for CAR-T cell therapy induced cytokine release syndrome. Frontiers in molecular medicine 1 39359418
2024 Four functional genotoxic marker genes (Bax, Btg2, Ccng1, and Cdkn1a) discriminate genotoxic hepatocarcinogens from non-genotoxic hepatocarcinogens and non-genotoxic non-hepatocarcinogens in rat public toxicogenomics data, Open TG-GATEs. Genes and environment : the official journal of the Japanese Environmental Mutagen Society 1 39702344
2023 Early-stage CCNG1+ HR+ HER2+ Invasive Breast Carcinoma in Older Women: Current Treatment and Future Perspectives for DeltaRex-G, a CCNG1 Inhibitor. Anticancer research 1 37247916
2015 [Molecular cloning and tissue expression of the CCNG1 gene in sheep]. Yi chuan = Hereditas 1 25881703
2026 Kupffer Cell-Derived Interleukin-6 Aggravates Radiation-Induced Liver Disease by Activating Hepatocyte STAT3 to Promote Ccng1 Transcription. Advances in radiation oncology 0 41783157
2026 Analysis of Clinical Benefit Using DNG64-CAR-V Chimeric Tumor Targeted Amphotropic RNA Vector in CCNG1 Expressing Cancers. Anticancer research 0 41895777
2018 Erratum: miR-23b suppresses lung carcinoma cell proliferation through CCNG1. Oncology letters 0 30675267

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