Affinage

CCND2

G1/S-specific cyclin-D2 · UniProt P30279

Length
289 aa
Mass
33.1 kDa
Annotated
2026-04-28
100 papers in source corpus 25 papers cited in narrative 25 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CCND2 encodes cyclin D2, a D-type cyclin that partners with CDK4/6 to phosphorylate the retinoblastoma protein (RB), thereby driving G1-to-S phase cell cycle progression in diverse cell types including neural progenitors, hematopoietic cells, and cardiomyocytes (PMID:24705253, PMID:27843138, PMID:29018036). CCND2 transcription is activated by STAT3 and SMAD3 and repressed by Elf5, CREM repressor isoforms, PRC2.1 (MTF2)-dependent H3K27me3 deposition, and promoter DNA methylation, while its mRNA is post-transcriptionally regulated by multiple miRNAs (let-7a, miR-1, miR-29, miR-135a, miR-194-5p) and stabilized by RNA-binding proteins IGF2BP3 and ELAVL1 (PMID:31511084, PMID:20831799, PMID:18431519, PMID:39903505, PMID:27583477, PMID:20418948, PMID:35033075). Cyclin D2 protein turnover is controlled by GSK-3β phosphorylation near Thr280, which triggers proteasomal degradation; gain-of-function mutations disrupting this degron cause protein stabilization and megalencephaly, whereas proximal loss-of-function variants cause microcephaly, establishing CCND2 as a dosage-sensitive regulator of human brain size (PMID:24705253, PMID:34087052). Forced CCND2 expression is sufficient to reactivate the cell cycle in post-mitotic cardiomyocytes and promote myocardial repair after infarction in mouse and pig models (PMID:29018036, PMID:37565345).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 2008 High

    Establishing that CCND2 is essential for myeloma cell proliferation and that its transcription can be blocked by CREM repressor isoforms resolved how oncogenic signals converge on CCND2 in multiple myeloma.

    Evidence RNAi knockdown and pharmacological CCND2 transcription inhibition via CREM induction in myeloma cells and xenografts

    PMID:18431519

    Open questions at the time
    • Identities of all trans-activating oncogenic signals at the CCND2 promoter in myeloma were not mapped
    • No structural data on how CREM isoforms occupy the CCND2 promoter
  2. 2010 High

    Demonstrating that let-7a and Elf5 directly repress CCND2 through its 3′UTR and proximal promoter, respectively, established the first direct post-transcriptional and transcriptional repressors of CCND2.

    Evidence 3′UTR luciferase reporter for let-7a in prostate cancer cells; ChIP and promoter reporter for Elf5 in mammary epithelial cells and Elf5-null mice

    PMID:20418948 PMID:20831799

    Open questions at the time
    • Whether let-7a and Elf5 act cooperatively in any shared tissue was not tested
    • Quantitative contribution of Elf5 versus other repressors in vivo unknown
  3. 2012 Medium

    Identification of miR-1, miR-206, and miR-29 as additional 3′UTR-targeting miRNAs of CCND2 broadened the network of post-transcriptional regulators and linked them to G1 arrest in rhabdomyosarcoma, while GATA1 was implicated in CCND2 transcriptional repression during erythroid differentiation.

    Evidence Luciferase reporter and cell cycle analysis in rhabdomyosarcoma cells; expression profiling of GATA1FL versus GATA1s in K562 erythroid differentiation

    PMID:21752897 PMID:22330340 PMID:22853316

    Open questions at the time
    • GATA1 binding at the CCND2 promoter was not directly demonstrated by ChIP
    • Relative potency among miR-1, miR-206, and miR-29 on CCND2 not quantified
  4. 2014 High

    Discovery that gain-of-function CCND2 mutations near Thr280 resist GSK-3β-mediated proteasomal degradation and cause excessive neural progenitor proliferation established the post-translational degradation mechanism and linked it to megalencephaly–polymicrogyria–polydactyly–hydrocephalus syndrome.

    Evidence In vitro proteasomal degradation assay, mutagenesis, in utero electroporation of embryonic mouse brain, patient-derived cell studies

    PMID:24705253

    Open questions at the time
    • Crystal structure of the degron/GSK-3β interaction not resolved
    • Whether additional kinases phosphorylate Thr280 in vivo is unknown
  5. 2016 Medium

    Demonstration of CCND2 promoter hypermethylation as a silencing mechanism in renal cell cancer and identification of FoxO1-dependent transcriptional regulation via linc00598 expanded the epigenetic and transcriptional regulatory landscape of CCND2.

    Evidence Methylation-specific PCR, bisulfite sequencing, 5-Aza demethylation rescue in RCC lines; lncRNA knockdown with promoter reporter and cell cycle analysis

    PMID:27572135 PMID:27583477

    Open questions at the time
    • Direct FoxO1 binding at the CCND2 promoter was not validated by ChIP
    • Whether promoter methylation and PRC2-mediated repression act on the same CpG island was not compared
  6. 2017 High

    Proving that CCND2 overexpression is sufficient to reactivate cell cycle in post-mitotic cardiomyocytes and promote myocardial repair after infarction opened a therapeutic avenue for cardiac regeneration.

    Evidence Lentiviral CCND2 overexpression in hiPSC-derived cardiomyocytes, Ki67 quantification, mouse myocardial infarction model

    PMID:29018036

    Open questions at the time
    • Whether CCND2-driven cardiomyocyte division produces functionally mature daughter cells was not resolved
    • Long-term arrhythmogenic risk not fully assessed
  7. 2019 High

    Multiple discoveries converged on CCND2 regulation: STAT3 was shown to directly activate the CCND2 promoter; PRC2 (via PICOT/EED) deposits H3K27me3 at the CCND2 locus to silence it; and CCND2-overexpressing cardiomyocytes electrically integrate with host myocardium, confirming functional coupling.

    Evidence ChIP for STAT3 at CCND2 promoter in CRC; co-IP/ChIP for PICOT-EED-H3K27me3 at CCND2 in T cells; optical mapping of engrafted cardiomyocytes in mouse

    PMID:31511084 PMID:31527584 PMID:31629738

    Open questions at the time
    • Whether STAT3 and PRC2 antagonistically regulate CCND2 at the same locus in any single cell type is untested
    • Electrophysiological integration data limited to single lab and timepoint
  8. 2021 Medium

    Reciprocal genotype–phenotype mapping of CCND2 variants (proximal loss-of-function causing microcephaly, distal stabilizing variants causing megalencephaly) established cyclin D2 as a dosage-sensitive determinant of human brain size, while RNA-binding protein IGF2BP3 was identified as a direct stabilizer of CCND2 mRNA.

    Evidence Clinical genetics of five patients from three families; RNA pull-down and RIP confirming IGF2BP3-CCND2 mRNA interaction in colorectal cancer cells

    PMID:34087052 PMID:35033075

    Open questions at the time
    • Functional rescue of loss-of-function variants was not performed
    • Quantitative contribution of IGF2BP3 versus miRNA-mediated decay not determined
  9. 2021 High

    Identification of the CCND2 Thr280Ala gain-of-function mutation as a driver of increased RB phosphorylation and proliferation in AML extended the degron-disruption mechanism from brain overgrowth to hematologic malignancy.

    Evidence Site-directed mutagenesis, RB phosphorylation assay, cell cycle and proliferation analysis in t(8;21) AML cell lines

    PMID:27843138

    Open questions at the time
    • In vivo leukemogenic potential of CCND2 T280A alone was not tested
    • Whether other AML-associated CCND2 mutations act through the same degron mechanism is unresolved
  10. 2023 High

    Translational validation that CCND2 modified mRNA delivery promotes cardiomyocyte proliferation and reduces infarct size across two large-animal-relevant models (mouse and pig) strengthened the therapeutic rationale, while PI3K/AKT inhibition was shown to trigger CCND2 degradation via GSK-3β dephosphorylation in lymphoma.

    Evidence Cardiomyocyte-specific modRNA delivery with Ki67/Aurora B quantification in mouse and pig MI models; pharmacological GSK-3β modulation with RB phosphorylation readout in BIA-ALCL

    PMID:37565345 PMID:37647808

    Open questions at the time
    • Long-term safety of transient CCND2 induction in heart not established
    • Whether GSK-3β is the sole kinase controlling CCND2 stability in all lineages remains unclear
  11. 2025 High

    Genetic dissection of PRC2 subcomplexes revealed that PRC2.1 (MTF2-containing), not PRC2.2 (JARID2-containing), is specifically responsible for H3K27me3 at CCND2 CpG islands and that MTF2 loss upregulates CCND2 sufficiently to confer resistance to CDK4/6 inhibitors.

    Evidence ChIP-seq for H3K27me3, genetic epistasis between MTF2 and JARID2, palbociclib sensitivity assays across multiple cell lines

    PMID:39903505

    Open questions at the time
    • Whether PRC2.1-specific recruitment involves DNA shape recognition at CCND2 CpG islands is not resolved
    • Clinical prevalence of MTF2 loss as a resistance mechanism to CDK4/6 inhibitors is unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • Major unresolved questions include the structural basis of cyclin D2–CDK4/6 complex formation and substrate selectivity, whether the diverse transcriptional and post-transcriptional inputs on CCND2 are integrated in a tissue-specific hierarchy, and whether therapeutic CCND2 modulation in the heart carries long-term oncogenic or arrhythmogenic risk.
  • No crystal structure of cyclin D2–CDK4 complex exists
  • Tissue-specific integration of CCND2 regulatory inputs not systematically mapped
  • Long-term safety of cardiac CCND2 induction not established

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 5
Localization
GO:0005634 nucleus 4
Pathway
R-HSA-1640170 Cell Cycle 8 R-HSA-4839726 Chromatin organization 4 R-HSA-74160 Gene expression (Transcription) 4 R-HSA-162582 Signal Transduction 3
Partners
CDK4CDK6ELAVL1EZH2GSK3BIGF2BP3SRSF1STAT3
Complex memberships
Cyclin D2–CDK4Cyclin D2–CDK6

Evidence

Reading pass · 25 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2014 De novo CCND2 mutations clustered around a GSK-3β phosphorylation site render cyclin D2 resistant to proteasomal degradation in vitro; the PI3K-AKT pathway modulates GSK-3β activity, leading to similar CCND2 accumulation in cells with PIK3CA, PIK3R2, or AKT3 mutations. In utero electroporation of mutant CCND2 into embryonic mouse brains produced more proliferating progenitors and a smaller fraction exiting the cell cycle compared to wild-type CCND2. In vitro proteasomal degradation assay, in utero electroporation, cell cycle analysis, patient-derived cell studies Nature genetics High 24705253
2021 CCND2 Thr280Ala mutation (clustering around a conserved threonine residue) leads to increased phosphorylation of the retinoblastoma protein, causing significant cell cycle changes and increased proliferation of AML cell lines, establishing CCND2 gain-of-function mutations as drivers of cell cycle dysregulation in t(8;21) AML. Site-directed mutagenesis, retinoblastoma phosphorylation assay, cell cycle analysis, proliferation assays in AML cell lines Leukemia High 27843138
2019 STAT3 directly binds the CCND2 promoter, increasing CCND2 transcription as part of JAK2/STAT3/CCND2 signaling that promotes cancer stem cell persistence and radioresistance in colorectal cancer. Chromatin immunoprecipitation (ChIP), promoter reporter assay, JAK2/STAT3 inhibition experiments, patient-derived CRC cells and xenografts Journal of experimental & clinical cancer research High 31511084
2010 MicroRNA let-7a directly binds the 3'UTR of CCND2 mRNA, downregulating CCND2 protein expression and inducing G1/S cell cycle arrest in prostate cancer cells. Dual-luciferase reporter assay, western blotting, cell cycle analysis, xenograft model PloS one High 20418948
2017 Overexpression of CCND2 in human iPSC-derived cardiomyocytes activates cell cycle progression (3-7 fold upregulation of Ki67 and other proliferation markers), enhances engraftment after myocardial infarction in mice, and promotes remuscularization of injured myocardium. Lentiviral CCND2 overexpression, cell cycle marker quantification, mouse MI model with histological and functional assessment Circulation research High 29018036
2023 CCND2 modified mRNA delivered via a cardiomyocyte-specific SMRTs system induces CCND2 expression selectively in cardiomyocytes, activates cell cycle markers (Ki67, Aurora B kinase), promotes cardiomyocyte proliferation, and reduces infarct size in both mouse and pig MI models. Modified mRNA delivery system, cardiomyocyte-specific expression via miR-1/miR-208 regulation, Ki67/Aurora B quantification, echocardiography in mouse and pig MI models Circulation research High 37565345
2008 RNAi knockdown of CCND2 inhibits proliferation and is progressively cytotoxic in human myeloma cells; kinetin riboside suppresses CCND2 transcription by upregulating repressor isoforms of CREM (cAMP-response element modulator), blocking trans-activation of CCND2 by multiple myeloma oncogenes. RNAi knockdown, chemical library screen with cell-based CCND2 trans-activation assay, transcription factor reporter assay, primary myeloma cell studies, xenograft model The Journal of clinical investigation High 18431519
2019 PICOT protein binds to chromatin-associated EED (a PRC2 component) via its PICOT/Grx homology domains; PICOT knockdown reduces H3K27me3 mark and decreases EED and EZH2 occupancy at the CCND2 gene promoter, resulting in increased CCND2 mRNA and protein expression in T cells. Co-immunoprecipitation, ChIP, knockdown experiments, western blotting, qPCR, TCGA data correlation Cell death & disease High 31527584
2025 PRC2.1 (containing MTF2), but not PRC2.2 (containing JARID2), promotes H3K27me3 deposition at CpG islands in the CCND1 and CCND2 promoters; loss of MTF2 upregulates both cyclins and rescues cells from CDK4/6 inhibitor palbociclib-induced G1 arrest. Chemogenetic screen, genetic epistasis (MTF2 vs JARID2 mutation), ChIP-seq for H3K27me3, palbociclib sensitivity assays in multiple cell lines eLife High 39903505
2010 The ETS transcription factor Elf5 directly binds a genomic segment upstream of the Ccnd2 gene and transcriptionally represses Ccnd2 expression in mouse mammary gland; loss of Elf5 in vivo leads to upregulation of Ccnd2 in luminal mammary cells. ChIP-cloning, ChIP, promoter reporter assay, Elf5-null mammary epithelial cells and gland analysis BMC molecular biology High 20831799
2016 Long noncoding RNA linc00598 regulates CCND2 transcription through modulation of FoxO1 transcriptional activity at the CCND2 promoter; knockdown of linc00598 induces G0/G1 cell cycle arrest and inhibits proliferation. Microarray analysis, knockdown experiments, promoter reporter assay, cell cycle analysis Scientific reports Medium 27572135
2011 MiR-1 directly targets and represses CCND2 (favoring G1/S transition) in thyroid carcinoma cells; ectopic miR-1 expression inhibits thyroid carcinoma cell proliferation and migration, validated by 3'UTR reporter assays. Luciferase reporter assay, western blotting, functional proliferation and migration assays The Journal of clinical endocrinology and metabolism Medium 21752897
2012 MiR-1, miR-206, and miR-29 target the 3'UTR of CCND2 to regulate its expression in rhabdomyosarcoma; overexpression of miR-29 downregulates CCND2 and other cell cycle genes (E2F7), inducing G1 arrest and decreased cell proliferation. Ectopic miRNA expression, western blotting, cell cycle analysis, luciferase reporter assays Laboratory investigation Medium 22330340
2016 CCND2 promoter is silenced by aberrant methylation in renal cell cancer; treatment with the demethylating agent 5-Aza (with or without TSA) restores CCND2 expression in methylated RCC cell lines. Methylation-specific PCR (MSP), bisulfite genomic sequencing (BGS), 5-Aza/TSA treatment, expression analysis PloS one Medium 27583477
2018 CCND2 promoter hypermethylation silences CCND2 expression in lung and breast cancer; cell model assays show that CCND2 expression inhibits cancer cell growth and migration; antroquinonol D, a demethylating agent, upregulates CCND2 expression and causes cell cycle arrest. Genome-wide methylation analysis, quantitative MSP, cell proliferation and migration assays, drug treatment International journal of molecular sciences Medium 30308939
2019 CCND2 overexpression in hiPSC-derived cardiomyocytes results in electrical integration (coupling) with host myocardium 6 months after transplantation, with optical mapping confirming synchronized action potential propagation, alongside >50% replacement of myocardial scar tissue. Optical mapping of action potential propagation, histological quantification of engraftment, echocardiography Journal of molecular and cellular cardiology Medium 31629738
2021 CCND2 loss-of-function through proximal frameshift or stop-gain variants causes microcephaly, while distal terminal-exon variants causing protein stabilization lead to megalencephaly, demonstrating that distinct classes of CCND2 variants have reciprocal effects on human brain growth. Clinical genetics, variant mapping, phenotypic characterization of five individuals from three families American journal of medical genetics. Part A Medium 34087052
2019 lncRNA TUG1 promotes CCND2 expression by binding EZH2 to epigenetically silence miR-194-5p (via promoter hypermethylation); knockdown of TUG1 reduces EZH2 levels, relieves methylation of miR-194-5p, which then directly targets and suppresses CCND2 in bladder cancer. EZH2 knockdown, bisulfite sequencing of miR-194-5p promoter, dual-luciferase reporter assay for miR-194-5p/CCND2, western blotting Molecular therapy. Nucleic acids Medium 30925453
2023 PI3K/AKT inhibitor BEZ-235 induces dephosphorylation of GSK3β, leading to proteasomal degradation of CCND2 protein, dephosphorylation of RB, and G1 cell cycle arrest in BIA-ALCL; CDK4/6 inhibitor palbociclib also dephosphorylates RB and arrests cells in G1, confirming that CCND2 controls CDK4/6 activity and RB phosphorylation. Western blotting for RB phosphorylation, GSK3β phosphorylation, mTORC1 target S6; cell cycle analysis; pharmacological inhibition Leukemia research Medium 37647808
2012 GATA1s isoform (but not GATA1FL) fails to repress CCND2 during terminal erythroid differentiation of K562 cells, suggesting CCND2 is a target of GATA1-mediated transcriptional repression during hematopoietic differentiation. Transgenic K562 cells expressing GATA1s or GATA1FL, gene expression profiling during erythroid differentiation Journal of hematology & oncology Low 22853316
2021 ZFAS1 lncRNA acts as a ceRNA to sponge miR-150-5p, preventing miR-150-5p from downregulating CCND2; ZFAS1 knockdown reduces ferroptosis markers and cardiomyocyte injury in diabetic cardiomyopathy models, with effects reversed by miR-150-5p inhibition or CCND2 depletion, placing CCND2 downstream of the ZFAS1/miR-150-5p axis. Dual-luciferase reporter assay, RNA pull-down, in vitro high glucose cardiomyocyte model, db/db mouse model, ferroptosis marker measurement Journal of cellular and molecular medicine Medium 34609043
2021 CCND2 mRNA is stabilized by IGF2BP3 protein binding, preventing its degradation; hsa_circ_0000231 promotes CCND2 expression by both sponging miR-375 (ceRNA mechanism) and binding IGF2BP3 to prevent CCND2 mRNA degradation in colorectal cancer cells. RNA pull-down, RNA immunoprecipitation (RIP), dual-luciferase reporter assay, in vitro and in vivo functional assays Cancer cell international Medium 35033075
2022 miR-135a suppresses granulosa cell growth by directly targeting the 3'UTR of Ccnd2; the TGFBR1-SMAD3 pathway enhances Ccnd2 promoter activity and upregulates Ccnd2 expression; ESR2 (estrogen receptor 2) acts as a transcription factor binding the miR-135a promoter to decrease miR-135a transcription, establishing an ESR2/miR-135a/Tgfbr1/Ccnd2 regulatory axis. 3'UTR luciferase reporter assay, ChIP-qPCR for SMAD3 at Ccnd2 promoter and ESR2 at miR-135a promoter, subcellular localization analysis, miR-135a overexpression in granulosa cells Cells Medium 34440873
2019 SRSF1 and miR-135a competitively bind the 3'UTR region of CCND2 mRNA; SRSF1 overexpression represses degradation of CCND2 mRNA by outcompeting miR-135a, while SRSF1 knockdown inhibits airway smooth muscle cell proliferation by reducing CCND2 levels. RNA immunoprecipitation, RNA pull-down, dual-luciferase reporter assay, RNA degradation assay, flow cytometry Pulmonary pharmacology & therapeutics Medium 36280202
2023 ELAVL1 (HuR) stabilizes CCND2 mRNA and counteracts miR-188-5p-mediated suppression of CCND2 in ovarian cancer cells; competition between miR-188-5p and HuR for CCND2 mRNA modulates CCND2 protein levels and ovarian cancer cell proliferation and migration. RIP assay, luciferase reporter assay, functional rescue experiments Cellular and molecular biology Low 37300687

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2019 The JAK2/STAT3/CCND2 Axis promotes colorectal Cancer stem cell persistence and radioresistance. Journal of experimental & clinical cancer research : CR 236 31511084
2010 MicroRNA let-7a inhibits proliferation of human prostate cancer cells in vitro and in vivo by targeting E2F2 and CCND2. PloS one 200 20418948
1999 Amplification and expression of cyclin D genes (CCND1, CCND2 and CCND3) in human malignant gliomas. Brain pathology (Zurich, Switzerland) 142 10416984
2012 CCND2 rearrangements are the most frequent genetic events in cyclin D1(-) mantle cell lymphoma. Blood 132 23255553
2017 CCND2 Overexpression Enhances the Regenerative Potency of Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes: Remuscularization of Injured Ventricle. Circulation research 129 29018036
2014 De novo CCND2 mutations leading to stabilization of cyclin D2 cause megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome. Nature genetics 121 24705253
1996 Molecular characterization of 12p abnormalities in hematologic malignancies: deletion of KIP1, rearrangement of TEL, and amplification of CCND2. Blood 109 8547659
2011 MiR-1 is a tumor suppressor in thyroid carcinogenesis targeting CCND2, CXCR4, and SDF-1alpha. The Journal of clinical endocrinology and metabolism 98 21752897
2018 LncRNA HOTAIR Regulates CCND1 and CCND2 Expression by Sponging miR-206 in Ovarian Cancer. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 97 30205383
2008 Translocations targeting CCND2, CCND3, and MYCN do occur in t(11;14)-negative mantle cell lymphomas. Blood 94 18391076
2021 Inhibition of the long non-coding RNA ZFAS1 attenuates ferroptosis by sponging miR-150-5p and activates CCND2 against diabetic cardiomyopathy. Journal of cellular and molecular medicine 93 34609043
2019 lncRNA TUG1 Promotes Cisplatin Resistance by Regulating CCND2 via Epigenetically Silencing miR-194-5p in Bladder Cancer. Molecular therapy. Nucleic acids 84 30925453
2012 Downregulation of microRNAs miR-1, -206 and -29 stabilizes PAX3 and CCND2 expression in rhabdomyosarcoma. Laboratory investigation; a journal of technical methods and pathology 83 22330340
2017 The long non-coding RNA HOTAIR promotes thyroid cancer cell growth, invasion and migration through the miR-1-CCND2 axis. American journal of cancer research 82 28670492
2016 MiR-146a-5p inhibits cell proliferation and cell cycle progression in NSCLC cell lines by targeting CCND1 and CCND2. Oncotarget 76 27494902
2018 CCND2 and CCND3 hijack immunoglobulin light-chain enhancers in cyclin D1- mantle cell lymphoma. Blood 75 30538135
2019 Circular RNA circ-RAD23B promotes cell growth and invasion by miR-593-3p/CCND2 and miR-653-5p/TIAM1 pathways in non-small cell lung cancer. Biochemical and biophysical research communications 60 30722989
2018 Hypermethylation of CCND2 in Lung and Breast Cancer Is a Potential Biomarker and Drug Target. International journal of molecular sciences 58 30308939
2013 miR-154 inhibits prostate cancer cell proliferation by targeting CCND2. Urologic oncology 55 23428540
2008 Identification of kinetin riboside as a repressor of CCND1 and CCND2 with preclinical antimyeloma activity. The Journal of clinical investigation 53 18431519
2016 Mutations in the CCND1 and CCND2 genes are frequent events in adult patients with t(8;21)(q22;q22) acute myeloid leukemia. Leukemia 52 27843138
2019 Suppression of miRNA let-7i-5p promotes cardiomyocyte proliferation and repairs heart function post injury by targetting CCND2 and E2F2. Clinical science (London, England : 1979) 46 30679264
2016 Highly expressed lncRNA CCND2-AS1 promotes glioma cell proliferation through Wnt/β-catenin signaling. Biochemical and biophysical research communications 44 27923660
2018 miR-4317 suppresses non-small cell lung cancer (NSCLC) by targeting fibroblast growth factor 9 (FGF9) and cyclin D2 (CCND2). Journal of experimental & clinical cancer research : CR 43 30227870
2023 CCND2 Modified mRNA Activates Cell Cycle of Cardiomyocytes in Hearts With Myocardial Infarction in Mice and Pigs. Circulation research 42 37565345
2021 Exosomal transfer of circ_0006174 contributes to the chemoresistance of doxorubicin in colorectal cancer by depending on the miR-1205/CCND2 axis. Journal of physiology and biochemistry 42 34792792
2018 Long noncoding RNA FOXD2-AS1 promotes glioma malignancy and tumorigenesis via targeting miR-185-5p/CCND2 axis. Journal of cellular biochemistry 41 30520141
2015 microRNA-195 inhibits the proliferation, migration and invasion of cervical cancer cells via the inhibition of CCND2 and MYB expression. Oncology letters 40 26622903
2019 Long noncoding RNA LINC00511 induced by SP1 accelerates the glioma progression through targeting miR-124-3p/CCND2 axis. Journal of cellular and molecular medicine 39 30973678
2019 miR‑145 suppresses ovarian cancer progression via modulation of cell growth and invasion by targeting CCND2 and E2F3. Molecular medicine reports 34 30864742
2020 MiR-646 suppresses proliferation and metastasis of non-small cell lung cancer by repressing FGF2 and CCND2. Cancer medicine 32 32347652
2020 Circular RNA CircHIPK3 Elevates CCND2 Expression and Promotes Cell Proliferation and Invasion Through miR-124 in Glioma. Frontiers in genetics 32 33005182
2016 Overexpression of miR-26b-5p regulates the cell cycle by targeting CCND2 in GC-2 cells under exposure to extremely low frequency electromagnetic fields. Cell cycle (Georgetown, Tex.) 32 26637059
2018 MiR-373-3p enhances the chemosensitivity of gemcitabine through cell cycle pathway by targeting CCND2 in pancreatic carcinoma cells. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 31 30021382
2020 CircRSF1 contributes to endothelial cell growth, migration and tube formation under ox-LDL stress through regulating miR-758/CCND2 axis. Life sciences 27 32791147
2019 LncRNA GAS8-AS1 suppresses papillary thyroid carcinoma cell growth through the miR-135b-5p/CCND2 axis. Bioscience reports 26 30429236
2018 LncRNA CCND2-AS1 promotes proliferation, migration, and invasion in papillary thyroid carcinoma. Biochemical and biophysical research communications 26 29366479
2021 LncRNA PRNCR1 Promotes Breast Cancer Proliferation and Inhibits Apoptosis by Modulating microRNA-377/CCND2/MEK/MAPK Axis. Archives of medical research 25 33608112
2019 MiR-34b-3p Represses the Multidrug-Chemoresistance of Bladder Cancer Cells by Regulating the CCND2 and P2RY1 Genes. Medical science monitor : international medical journal of experimental and clinical research 25 30778022
2019 LncRNA KCNQ1OT1 acting as a ceRNA for miR-4458 enhances osteosarcoma progression by regulating CCND2 expression. In vitro cellular & developmental biology. Animal 25 31392505
2021 Notoginsenoside R1 attenuates breast cancer progression by targeting CCND2 and YBX3. Chinese medical journal 23 33480613
2021 Proximal variants in CCND2 associated with microcephaly, short stature, and developmental delay: A case series and review of inverse brain growth phenotypes. American journal of medical genetics. Part A 23 34087052
2019 miR‑671‑3p is downregulated in non‑small cell lung cancer and inhibits cancer progression by directly targeting CCND2. Molecular medicine reports 23 30664171
2018 Hypoglycaemia represents a clinically significant manifestation of PIK3CA- and CCND2-associated segmental overgrowth. Clinical genetics 23 28941273
2016 MicroRNA-610 suppresses the proliferation of human glioblastoma cells by repressing CCND2 and AKT3. Molecular medicine reports 23 26782072
2019 Cardiomyocytes from CCND2-overexpressing human induced-pluripotent stem cells repopulate the myocardial scar in mice: A 6-month study. Journal of molecular and cellular cardiology 22 31629738
2013 Fangchinoline induces G0/G1 arrest by modulating the expression of CDKN1A and CCND2 in K562 human chronic myelogenous leukemia cells. Experimental and therapeutic medicine 21 23596478
2012 A new microRNA target prediction tool identifies a novel interaction of a putative miRNA with CCND2. RNA biology 21 22954617
2015 CCND2, CTNNB1, DDX3X, GLI2, SMARCA4, MYC, MYCN, PTCH1, TP53, and MLL2 gene variants and risk of childhood medulloblastoma. Journal of neuro-oncology 20 26290144
2020 Amniotic fluid mesenchymal stem cells repair mouse corneal cold injury by promoting mRNA N4-acetylcytidine modification and ETV4/JUN/CCND2 signal axis activation. Human cell 19 33010000
2018 Effect of miR-29b on the Proliferation and Apoptosis of Pulmonary Artery Smooth Muscle Cells by Targeting Mcl-1 and CCND2. BioMed research international 19 29662889
2016 The Silencing of CCND2 by Promoter Aberrant Methylation in Renal Cell Cancer and Analysis of the Correlation between CCND2 Methylation Status and Clinical Features. PloS one 19 27583477
2023 LncRNA AC005332.7 Inhibited Ferroptosis to Alleviate Acute Myocardial Infarction Through Regulating miR-331-3p/CCND2 Axis. Korean circulation journal 18 36914604
2021 Circ-PITX1 Promotes the Progression of Non-Small Cell Lung Cancer Through Regulating the miR-1248/CCND2 Axis. OncoTargets and therapy 18 33727831
2019 MiRNA-574-3p inhibits cell progression by directly targeting CCND2 in colorectal cancer. Bioscience reports 18 31729531
2010 CCND2 polymorphisms associated with clearance of HBV infection. Journal of human genetics 17 20414251
2021 Long intergenic non-coding RNA 00473 promotes proliferation and migration of gastric cancer via the miR-16-5p/CCND2 axis and by regulating AQP3. Cell death & disease 16 33993193
2021 KDM4C contributes to cytarabine resistance in acute myeloid leukemia via regulating the miR-328-3p/CCND2 axis through MALAT1. Therapeutic advances in chronic disease 16 34394903
2018 MicroRNA-2682-3p inhibits osteosarcoma cell proliferation by targeting CCND2, MMP8 and Myd88. Oncology letters 16 30127935
2016 miR-26a regulates mouse hepatocyte proliferation via directly targeting the 3' untranslated region of CCND2 and CCNE2. Hepatobiliary & pancreatic diseases international : HBPD INT 16 26818545
2010 Genome-wide search identifies Ccnd2 as a direct transcriptional target of Elf5 in mouse mammary gland. BMC molecular biology 16 20831799
2022 Downregulation of Kcnq1ot1 attenuates β-cell proliferation and insulin secretion via the miR-15b-5p/Ccnd1 and Ccnd2 axis. Acta diabetologica 15 35347427
2016 Long noncoding RNA linc00598 regulates CCND2 transcription and modulates the G1 checkpoint. Scientific reports 15 27572135
2021 Circ_0093887 upregulates CCND2 and SUCNR1 to inhibit the ox-LDL-induced endothelial dysfunction in atherosclerosis by functioning as a miR-876-3p sponge. Clinical and experimental pharmacology & physiology 14 33844344
2012 The GATA1s isoform is normally down-regulated during terminal haematopoietic differentiation and over-expression leads to failure to repress MYB, CCND2 and SKI during erythroid differentiation of K562 cells. Journal of hematology & oncology 14 22853316
2022 The MyoD1 Promoted Muscle Differentiation and Generation by Activating CCND2 in Guanling Cattle. Animals : an open access journal from MDPI 13 36230312
2017 Genetic association analysis of the RTK/ERK pathway with aggressive prostate cancer highlights the potential role of CCND2 in disease progression. Scientific reports 13 28674394
2022 Long noncoding RNA FAM225B facilitates proliferation and metastasis of nasopharyngeal carcinoma cells by regulating miR-613/CCND2 axis. Bosnian journal of basic medical sciences 12 34255617
2022 hsa_circ_0000231 Promotes colorectal cancer cell growth through upregulation of CCND2 by IGF2BP3/miR-375 dual pathway. Cancer cell international 12 35033075
2021 miR-135a Suppresses Granulosa Cell Growth by Targeting Tgfbr1 and Ccnd2 during Folliculogenesis in Mice. Cells 12 34440873
2020 miR-451a suppresses the development of breast cancer via targeted inhibition of CCND2. Molecular and cellular probes 12 32828867
2019 UCA1 promotes cell viability, proliferation and migration potential through UCA1/miR-204/CCND2 pathway in primary cystitis glandularis cells. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 12 30999112
2011 Hypermethylation of CCND2 May Reflect a Smoking-Induced Precancerous Change in the Lung. Journal of oncology 12 21577262
2022 miR-93-5p suppresses ovarian cancer malignancy and negatively regulate CCND2 by binding to its 3'UTR region. Discover oncology 11 35306579
2022 Fine Mapping of a Major Backfat QTL Reveals a Causal Regulatory Variant Affecting the CCND2 Gene. Frontiers in genetics 11 35692822
2021 Hsa_circ_0008360 sponges miR-186-5p to target CCND2 to modulate high glucose-induced vascular endothelial dysfunction. Cell cycle (Georgetown, Tex.) 11 34223793
2022 LncRNA RP11‑805J14.5 functions as a ceRNA to regulate CCND2 by sponging miR‑34b‑3p and miR‑139‑5p in lung adenocarcinoma. Oncology reports 10 35866595
2011 CD5-positive, cyclinD1-negative mantle cell lymphoma with a translocation involving the CCND2 gene and the IGL locus. Cancer genetics 10 21504716
2022 miR-1297 inhibits osteosarcoma cell proliferation and growth by targeting CCND2. American journal of cancer research 8 35968334
2021 CircTHBS1 targeting miR-211/CCND2 pathway to promote cell proliferation and migration potential in primary cystitis glandularis cells. Bioscience reports 8 32820798
2023 Ndufa4 Regulates the Proliferation and Apoptosis of Neurons via miR-145a-5p/Homer1/Ccnd2. Molecular neurobiology 7 36763283
2020 Measurement of Cyclin D2 (CCND2) Gene Promoter Methylation in Plasma and Peripheral Blood Mononuclear Cells and Alpha-Fetoprotein Levels in Patients with Hepatitis B Virus-Associated Hepatocellular Carcinoma. Medical science monitor : international medical journal of experimental and clinical research 7 33320844
2019 Severe presentation and complex brain malformations in an individual carrying a CCND2 variant. Molecular genetics & genomic medicine 7 31056854
2019 PICOT binding to chromatin-associated EED negatively regulates cyclin D2 expression by increasing H3K27me3 at the CCND2 gene promoter. Cell death & disease 7 31527584
1998 Genomic amplification of CCND2 is rare in non-Hodgkin lymphomas. Cancer genetics and cytogenetics 7 9530346
2023 CCND2 and miR-206 as potential biomarkers in the clinical diagnosis of thyroid carcinoma by fine-needle aspiration cytology. World journal of surgical oncology 6 36694220
2023 GABA regulates the proliferation and apoptosis of head and neck squamous cell carcinoma cells by promoting the expression of CCND2 and BCL2L1. Life sciences 6 37866807
2020 LncRNA XIST acts as a ceRNA sponging miR-185-5p to modulate pancreatic cancer cell proliferation via targeting CCND2. Translational cancer research 6 35117490
2014 Association between the polymorphism rs3217927 of CCND2 and the risk of childhood acute lymphoblastic leukemia in a Chinese population. PloS one 6 24743557
1994 Coamplification in human breast-tumors and physical linkage at chromosomal band 12p13, of ccnd2 and fgf6 genes. International journal of oncology 6 21559724
2022 Gene identification and functional analysis of a D-type cyclin (CCND2) in freshwater pearl mussel (Hyriopsis cumingii). Molecular biology reports 5 35616759
2022 Interaction of CCND2, CDKN1A, and POLD3 Variants in Mexican Patients with Colorectal Cancer. The Turkish journal of gastroenterology : the official journal of Turkish Society of Gastroenterology 5 35786622
2022 SRSF1 promotes ASMC proliferation in asthma by competitively binding CCND2 with miRNA-135a. Pulmonary pharmacology & therapeutics 5 36280202
2021 Reduced expression of microRNA-432-5p by DNA methyltransferase 3B leads to development of colorectal cancer through upregulation of CCND2. Experimental cell research 5 34801563
2025 The PRC2.1 subcomplex opposes G1 progression through regulation of CCND1 and CCND2. eLife 4 39903505
2023 MiR-188-5p inhibits cell proliferation and migration in ovarian cancer via competing for CCND2 with ELAVL1. Cellular and molecular biology (Noisy-le-Grand, France) 4 37300687
2023 PI3K/AKT inhibitor BEZ-235 targets CCND2 and induces G1 arrest in breast implant-associated anaplastic large cell lymphoma. Leukemia research 4 37647808
2022 Prenatal diagnosis of microcephaly as shown by plateauing of head circumference growth during the 3rd trimester in a fetus with a CCND2 inverse growth variant. Prenatal diagnosis 4 35437818
2020 Aberrant methylation-mediated downregulation of lncRNA CCND2 AS1 promotes cell proliferation in cervical cancer. Journal of biological research (Thessalonike, Greece) 4 32607313
2018 LncRNA CCND2-AS1 is up-regulated and regulates proliferation, migration, and invasion in breast cancer. International journal of clinical and experimental pathology 4 31938243