Affinage

CCNB2

G2/mitotic-specific cyclin-B2 · UniProt O95067

Length
398 aa
Mass
45.3 kDa
Annotated
2026-06-09
30 papers in source corpus 12 papers cited in narrative 11 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 4/4 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CCNB2 (Cyclin B2) is a cell cycle regulator required for the G2/M transition, whose loss across diverse cancer cell types blocks G2/M progression, suppresses proliferation and migration, and induces apoptosis (PMID:35261781, PMID:39962178, PMID:34838000). Its expression is set by multiple upstream inputs: direct transcriptional activation through promoter binding by HMGA1/HMGA2 (PMID:19223528) and ISL1 (PMID:27183908), regulation by the kinase PBK (PMID:31874375) and the importin KPNA2 acting upstream of a CCNB2/CDK1 module (PMID:29435009), positive control by the m6A reader YTHDC2 at the protein level (PMID:34822792), and post-transcriptional repression via direct 3'-UTR targeting by miR-335-5p (PMID:32636645) and miR-205 (PMID:32194761). Beyond canonical cell cycle control, CCNB2 promotes malignant behavior in gastric cancer by activating PI3K/AKT signaling and driving EMT, an axis counteracted by RHBDL2 (PMID:39962178, PMID:34838000). In early mammalian embryogenesis CCNB2 is required for proper chromosomal organization and zygotic genome activation, acting downstream of a sperm-derived circRNA-1572/miRNA axis (PMID:40091686). The biochemical activity of the Cyclin B2 protein itself, including its partner kinase and substrate engagement, is not characterized in the available corpus.

Mechanistic history

Synthesis pass · year-by-year structured walk · 10 steps
  1. 2009 High

    Established a direct transcriptional mechanism for CCNB2 overexpression by showing HMGA1/HMGA2 bind its promoter and drive its activity, linking architectural transcription factors to cyclin B2 dysregulation.

    Evidence EMSA, ChIP, and luciferase promoter assays in pituitary adenoma context

    PMID:19223528

    Open questions at the time
    • Does not address whether CCNB2 protein activity or stability is altered downstream
    • Promoter regulation shown in one tumor type only
  2. 2016 Medium

    Identified ISL1 as a second direct transcriptional activator of CCNB2, connecting its expression to G2/M progression in gastric cancer.

    Evidence ChIP and promoter binding with ISL1 knockdown/overexpression and flow cytometry cell cycle analysis

    PMID:27183908

    Open questions at the time
    • Single lab
    • Does not establish whether ISL1 and HMGA inputs converge or act independently
  3. 2017 Medium

    Placed KPNA2 upstream of a CCNB2/CDK1 module in hepatocellular carcinoma, broadening the set of regulators controlling CCNB2-driven G2/M transit.

    Evidence KPNA2 RNAi knockdown with RT-qPCR and flow cytometry cell cycle analysis

    PMID:29435009

    Open questions at the time
    • Mechanism by which KPNA2 controls CCNB2 transcript levels unresolved
    • Correlative expression rather than direct binding
  4. 2019 Medium

    Linked the kinase PBK to CCNB2 expression in glioblastoma, tying CCNB2 levels to tumorigenesis and radio-resistance.

    Evidence PBK knockdown/inhibition in vitro and in vivo with CCNB2 measurement and radiation sensitivity assays

    PMID:31874375

    Open questions at the time
    • Whether regulation is direct or indirect not defined
    • No structural or biochemical link between PBK and the CCNB2 promoter
  5. 2020 Medium

    Demonstrated post-transcriptional repression of CCNB2 by direct 3'-UTR targeting from miR-335-5p and miR-205, with rescue confirming CCNB2 as the functional effector controlling proliferation and migration.

    Evidence Dual-luciferase reporter assays plus miRNA overexpression and CCNB2 rescue in lung adenocarcinoma and thyroid cancer cells

    PMID:32194761 PMID:32636645

    Open questions at the time
    • Single lab per study
    • Relative contribution of each miRNA in vivo not established
  6. 2021 Medium

    Added an m6A-dependent layer of positive regulation, showing the reader YTHDC2 raises CCNB2 protein to relieve G2/M arrest and reproductive toxicity in spermatogonia.

    Evidence YTHDC2 overexpression with CCNB2 protein measurement, flow cytometry, and mouse testis histology

    PMID:34822792

    Open questions at the time
    • Direct m6A modification of CCNB2 transcript not mapped
    • Single lab
  7. 2021 Medium

    Defined CCNB2 as a driver of malignant phenotypes beyond cell cycle control, activating PI3K/AKT signaling and EMT in gastric cancer and rhabdomyosarcoma, with RHBDL2 acting as an antagonist.

    Evidence CCNB2 knockdown/overexpression with RNA-seq pathway analysis, functional assays, and RHBDL2 rescue

    PMID:34838000 PMID:39962178

    Open questions at the time
    • Mechanism linking cyclin B2 to PI3K/AKT activation undefined
    • Single labs
  8. 2022 Medium

    Consolidated the core CCNB2 loss-of-function phenotype across cancer, showing knockdown blocks G2/M, reduces proliferation/migration, increases apoptosis, and impairs endothelial transmigration relevant to lymphovascular invasion.

    Evidence CCNB2 knockdown with proliferation, apoptosis, cell cycle, and endothelial adherence/transmigration assays in breast cancer cells

    PMID:35261781

    Open questions at the time
    • Molecular basis of the transmigration phenotype not resolved
    • Single lab
  9. 2021 Low

    Proposed a non-canonical CCNB2 role in inducing a senescence-associated secretory phenotype that drives glioma progression via Cathepsin B and PGE2.

    Evidence Gene expression profiling and CCNB2 functional assays with SASP cytokine measurement in glioma cells

    PMID:34512164

    Open questions at the time
    • Limited mechanistic detail; how CCNB2 triggers SASP is unestablished
    • Single lab, not independently confirmed
  10. 2025 Medium

    Extended CCNB2 function to early embryogenesis, showing it acts downstream of a sperm-derived circRNA/miRNA axis and is required for chromosomal organization and zygotic genome activation, with mRNA supplementation rescuing the defects.

    Evidence circRNA knockdown, miRNA overexpression, CCNB2 mRNA rescue, transcriptome sequencing, and immunofluorescence in porcine embryos

    PMID:40091686

    Open questions at the time
    • Mechanism by which CCNB2 controls chromosomal organization not defined
    • Single lab, porcine model

Open questions

Synthesis pass · forward-looking unresolved questions
  • The intrinsic biochemical activity of the Cyclin B2 protein—its kinase partner, substrate engagement, and how its abundance is translated into G2/M control—remains uncharacterized in this corpus.
  • No structural model
  • No direct CDK partner or substrate assay
  • Mechanistic basis of G2/M control inferred from expression phenotypes only

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 2
Pathway
R-HSA-1643685 Disease 4 R-HSA-1640170 Cell Cycle 3 R-HSA-162582 Signal Transduction 1
Partners
CDK1

Evidence

Reading pass · 11 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2009 HMGA1 and HMGA2 proteins directly bind to the promoter of the CCNB2 gene (demonstrated by EMSA and ChIP) and transcriptionally upregulate CCNB2 promoter activity (demonstrated by luciferase reporter assay), contributing to cyclin B2 overexpression in pituitary adenomas. Electrophoretic mobility shift assay (EMSA), chromatin immunoprecipitation (ChIP), luciferase promoter activity assay Cancer research High 19223528
2016 ISL1 transcription factor activates CCNB2 expression in gastric cancer cells by directly binding to conserved binding sites on the CCNB2 promoter/enhancer, promoting G2/M cell cycle progression. Chromatin immunoprecipitation, promoter binding assay, ISL1 knockdown/overexpression with gene expression readout, flow cytometry cell cycle analysis Oncotarget Medium 27183908
2019 PBK (PDZ-binding kinase) transcriptionally regulates CCNB2 expression in glioblastoma cells; PBK-dependent upregulation of CCNB2 is critical for GBM tumorigenesis and radio-resistance. PBK inhibition/knockdown in vitro and in vivo with CCNB2 expression measurement, functional cell proliferation and radiation sensitivity assays Translational oncology Medium 31874375
2017 KPNA2 knockdown downregulates CCNB2 and CDK1, induces G2/M cell cycle arrest, and inhibits hepatocellular carcinoma cell proliferation, placing KPNA2 upstream of CCNB2/CDK1 in HCC cell cycle regulation. RNA interference knockdown of KPNA2, RT-qPCR for CCNB2/CDK1 expression, flow cytometry cell cycle analysis, proliferation assay Oncology letters Medium 29435009
2021 YTHDC2 (an m6A binding protein) positively regulates CCNB2 expression; overexpression of YTHDC2 increases CCNB2 protein levels and rescues G2/M cell cycle arrest and reproductive toxicity caused by manganese exposure in spermatogonia. YTHDC2 overexpression in spermatogonia with CCNB2 protein measurement, flow cytometry cell cycle analysis, in vivo mouse testis histomorphology Chemico-biological interactions Medium 34822792
2020 miR-335-5p directly targets the 3'-UTR of CCNB2 mRNA (validated by dual-luciferase reporter assay), reducing CCNB2 expression and thereby inhibiting LUAD cell proliferation, migration, and invasion; CCNB2 overexpression rescues these phenotypes. Dual-luciferase reporter assay, CCNB2 silencing, miR-335-5p overexpression, rescue experiments, MTT/colony formation/Transwell/flow cytometry assays OncoTargets and therapy Medium 32636645
2020 miR-205 directly targets CCNB2 mRNA (validated by luciferase reporter assay), and its overexpression reduces CCNB2 protein levels and inhibits thyroid cancer cell proliferation and migration; CCNB2 overexpression reverses these inhibitory effects. Luciferase reporter assay, qRT-PCR, Western blot, CCK-8 proliferation assay, Transwell migration assay, rescue experiment Oncology letters Medium 32194761
2022 Knockdown of CCNB2 in breast cancer cell lines reduces cell migration, inhibits proliferation, blocks G2/M cell cycle transition, increases apoptosis, and reduces adherence and transmigration across endothelial cell lines, demonstrating a role for CCNB2 in lymphovascular invasion. CCNB2 mRNA knockdown, cell migration/proliferation/apoptosis assays, flow cytometry cell cycle analysis, endothelial cell adherence and transmigration assays American journal of cancer research Medium 35261781
2021 CCNB2 knockdown inhibits gastric cancer and rhabdomyosarcoma cell growth, invasion, migration, and induces cell cycle arrest and apoptosis; CCNB2 overexpression promotes these phenotypes and activates the PI3K/AKT signaling pathway, with RHBDL2 overexpression able to counteract CCNB2-mediated EMT and PI3K/AKT activation. CCNB2 knockdown/overexpression, RNA sequencing pathway analysis, proliferation/invasion/migration assays, flow cytometry, Western blot for PI3K/AKT pathway components, rescue experiments with RHBDL2 Scientific reports / Cancer cell international Medium 34838000 39962178
2021 CCNB2 induces a senescence-associated secretory phenotype (SASP) in glioma cells, driving malignant progression (invasion and excessive proliferation) through secretion of SASP cytokines including Cathepsin B and PGE2. Gene expression profiling, CCNB2 functional assays in glioma cells with SASP cytokine measurement International journal of biological sciences Low 34512164
2025 In porcine embryogenesis, CCNB2 is regulated by the sperm-derived circRNA-1572/bta-miR-2478-L-2 axis; knockdown of circRNA-1572 or overexpression of bta-miR-2478-L-2 reduces CCNB2 mRNA and protein levels, causing aberrant chromosomal organization and impaired zygotic genome activation, which is rescued by CCNB2 mRNA supplementation. circRNA knockdown, miRNA overexpression, CCNB2 mRNA supplementation rescue, whole-transcriptome sequencing, SMART-seq, Western blot, immunofluorescence for F-actin and chromosomes Advanced science Medium 40091686

Source papers

Stage 0 corpus · 30 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2009 HMGA proteins up-regulate CCNB2 gene in mouse and human pituitary adenomas. Cancer research 86 19223528
2016 ISL1, a novel regulator of CCNB1, CCNB2 and c-MYC genes, promotes gastric cancer cell proliferation and tumor growth. Oncotarget 63 27183908
2020 miR-335-5p Regulates Cell Cycle and Metastasis in Lung Adenocarcinoma by Targeting CCNB2. OncoTargets and therapy 62 32636645
2007 Usefulness of CDK5RAP3, CCNB2, and RAGE genes for the diagnosis of lung adenocarcinoma. The International journal of biological markers 61 17549666
2017 Karyopherin subunit-α 2 expression accelerates cell cycle progression by upregulating CCNB2 and CDK1 in hepatocellular carcinoma. Oncology letters 59 29435009
2020 Knockdown of Circ_CCNB2 Sensitizes Prostate Cancer to Radiation Through Repressing Autophagy by the miR-30b-5p/KIF18A Axis. Cancer biotherapy & radiopharmaceuticals 44 32716640
2022 Upregulation of Cyclin B2 (CCNB2) in breast cancer contributes to the development of lymphovascular invasion. American journal of cancer research 30 35261781
2010 Use of serum circulating CCNB2 in cancer surveillance. The International journal of biological markers 30 21161946
2019 PDZ-Binding Kinase-Dependent Transcriptional Regulation of CCNB2 Promotes Tumorigenesis and Radio-Resistance in Glioblastoma. Translational oncology 28 31874375
2021 Cyclin B2 (CCNB2) Stimulates the Proliferation of Triple-Negative Breast Cancer (TNBC) Cells In Vitro and In Vivo. Disease markers 23 34354775
2021 Protective role of m6A binding protein YTHDC2 on CCNB2 in manganese-induced spermatogenesis dysfunction. Chemico-biological interactions 22 34822792
2021 CCNB2/SASP/Cathepsin B & PGE2 Axis Induce Cell Senescence Mediated Malignant Transformation. International journal of biological sciences 20 34512164
2022 CCNB1 and CCNB2 involvement in the pathogenesis of psoriasis: a bioinformatics study. The Journal of international medical research 15 35949173
2020 Roles of CCNB2 and NKX3-1 in Nasopharyngeal Carcinoma. Cancer biotherapy & radiopharmaceuticals 14 32202926
2020 CCNB2 and AURKA overexpression may cause atypical mitosis in Japanese cortisol-producing adrenocortical carcinoma with TP53 somatic variant. PloS one 13 32287321
2022 Upregulation of CCNB2 and Its Perspective Mechanisms in Cerebral Ischemic Stroke and All Subtypes of Lung Cancer: A Comprehensive Study. Frontiers in integrative neuroscience 12 35928585
2015 High EGFR_1 Inside-Out Activated Inflammation-Induced Motility through SLC2A1-CCNB2-HMMR-KIF11-NUSAP1-PRC1-UBE2C. Journal of Cancer 12 26000042
2021 Bioinformatics prediction and experimental verification identify MAD2L1 and CCNB2 as diagnostic biomarkers of rhabdomyosarcoma. Cancer cell international 10 34838000
2020 Effect of miR-205 on proliferation and migration of thyroid cancer cells by targeting CCNB2 and the mechanism. Oncology letters 10 32194761
2021 Identification of CCNB2 as A Potential Non-Invasive Breast Cancer Biomarker in Peripheral Blood Mononuclear Cells Using The Systems Biology Approach. Cell journal 9 34455715
2022 CCNB2 expression correlates with worse outcomes in breast cancer patients: a pooled analysis. Women & health 8 35892137
2025 Knockdown of CCNB2 inhibits the tumorigenesis of gastric cancer by regulation of the PI3K/Akt pathway. Scientific reports 7 39962178
2025 Sperm-Derived CircRNA-1572 Regulates Embryogenesis and Zygotic Genome Activation by Targeting CCNB2 via Bta-miR-2478-L-2. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 6 40091686
2023 CCNB2 as a potential biomarker of bladder cancer via the high throughput technology. Medicine 6 36820589
2022 Hsa_circ_0000285 knockdown inhibits the progression of hepatocellular carcinoma by sponging miR-582-3p to regulate CCNB2 expression. Human & experimental toxicology 6 35839486
2010 Use of serum circulating CCNB2 in cancer surveillance. The International journal of biological markers 5 21110300
2025 BUB1 and CCNB2 mediate cell cycle and inflammation, influencing the progression of oral squamous cell carcinoma. Journal of stomatology, oral and maxillofacial surgery 1 41151687
2026 CCNB2, NUSAP1, GTSE1, and TK1: potential dual biomarkers for pneumonia and lung adenocarcinoma. Cytotechnology 0 41908258
2025 Molecular docking and dynamics reveal CCNB2 as a functional target of lncRNA ADAMTS9-AS1-002 in HNSCC. Biochemical and biophysical research communications 0 41337866
2024 High Glycolytic Activity Signature Reveals CCNB2 as a Key Therapeutic Target in Triple-Negative Breast Cancer. Frontiers in bioscience (Landmark edition) 0 39206892

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