Affinage

CCND2

G1/S-specific cyclin-D2 · UniProt P30279

Length
289 aa
Mass
33.1 kDa
Annotated
2026-06-09
100 papers in source corpus 20 papers cited in narrative 20 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

CCND2 (cyclin D2) is a D-type cyclin that drives G1/S cell cycle progression, and its dosage governs the balance between proliferation and cell-cycle exit in contexts ranging from cortical neurogenesis to tumor growth (PMID:24705253, PMID:18431519). Cyclin D2 activity is read out through retinoblastoma protein (Rb) phosphorylation, with stabilized cyclin D2 increasing Rb phosphorylation to accelerate proliferation (PMID:27843138, PMID:37647808). Protein abundance is controlled by GSK-3β-dependent phosphorylation that targets cyclin D2 for proteasomal degradation; PI3K/AKT signaling inactivates GSK-3β to stabilize the protein, and pharmacologic PI3K/AKT inhibition restores GSK-3β activity, lowers cyclin D2, dephosphorylates Rb, and arrests cells in G1 (PMID:24705253, PMID:37647808). De novo mutations clustered around the GSK-3β phosphorylation threonine render cyclin D2 degradation-resistant and stabilized, expanding proliferating neural progenitors and causing megalencephaly-polymicrogyria-polydactyly-hydrocephalus (MPPH) syndrome, while N-terminal loss-of-function variants conversely cause microcephaly — establishing reciprocal brain-growth phenotypes from gain versus loss of cyclin D2 function (PMID:24705253, PMID:34087052); the same Thr280 gain-of-function stabilization drives proliferation in t(8;21) AML (PMID:27843138). Transcriptionally, CCND2 is activated by STAT3 binding its promoter downstream of JAK2/STAT3 and by SMAD3 downstream of TGFβR1, and is repressed by the ETS factor ELF5, by promoter DNA hypermethylation, and by PRC2.1 (MTF2)-deposited H3K27me3, a silencing layer modulated by PICOT/glutaredoxin-3 (PMID:31511084, PMID:34440873, PMID:20831799, PMID:27583477, PMID:31527584, PMID:39903505). Post-transcriptionally, CCND2 is a direct target of multiple microRNAs (let-7a, miR-1) and is stabilized by the RNA-binding protein ELAVL1/HuR and the splicing factor SRSF1 (PMID:20418948, PMID:21752897, PMID:36280202). Reflecting its proliferative output, CCND2 is essential for myeloma cell survival, and its forced overexpression reactivates the cell cycle in post-mitotic cardiomyocytes to drive myocardial repair (PMID:18431519, PMID:29018036, PMID:37565345).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 2008 High

    Established that tumor cells can be addicted to CCND2, defining it as a survival dependency and a druggable transcriptional node rather than a passive proliferation marker.

    Evidence RNAi knockdown and a CCND2 trans-activation screen (kinetin riboside / CREM repressor isoforms) in myeloma cells plus xenografts

    PMID:18431519

    Open questions at the time
    • Did not identify the direct transcription factors driving CCND2 trans-activation by myeloma oncogenes
    • Mechanism of CREM repressor isoform induction by kinetin riboside not resolved
  2. 2010 Medium

    Identified ELF5 as a direct transcriptional repressor of Ccnd2, showing CCND2 levels are constrained by lineage-specific ETS factors in epithelial tissue.

    Evidence ChIP-cloning, promoter reporter assay, and Elf5-null mammary epithelium analysis

    PMID:20831799

    Open questions at the time
    • Whether ELF5 repression is direct transcriptional or via recruited corepressors not defined
    • Generalizability beyond mammary lineage untested
  3. 2010 Medium

    Defined CCND2 as a direct post-transcriptional target of microRNAs, showing its protein output is set at the 3'UTR independent of transcription.

    Evidence Dual-luciferase 3'UTR reporter, western blot, cell cycle analysis, and xenograft for let-7a (and subsequently miR-1)

    PMID:20418948 PMID:21752897

    Open questions at the time
    • Relative contribution of miRNA vs transcriptional control in physiological settings unquantified
    • Did not address combinatorial miRNA regulation
  4. 2014 High

    Unified PI3K-AKT-related megalencephaly mechanistically by showing degradation-resistant CCND2 stabilization expands neural progenitors, answering how a single cyclin links a signaling pathway to brain overgrowth.

    Evidence In vitro proteasomal degradation assays, patient cell analysis, and in utero electroporation of mutant CCND2 in mouse brain

    PMID:24705253

    Open questions at the time
    • Direct demonstration of GSK-3β phosphorylation of the mutated residue inferred rather than enzymatically reconstituted
    • Downstream CDK partner engagement in progenitors not detailed
  5. 2016 Medium

    Extended the gain-of-function stabilization model to cancer, showing Thr280-region mutant CCND2 drives Rb phosphorylation and proliferation in AML.

    Evidence Mutant CCND2 expression, Rb phosphorylation assay, and cell cycle/proliferation analysis in AML cell lines

    PMID:27843138

    Open questions at the time
    • Direct measurement of mutant protein half-life not shown
    • Single-lab cell-line evidence without patient functional validation
  6. 2016 Medium

    Identified DNA promoter hypermethylation as a tumor-suppressive silencing mechanism of CCND2, showing its expression can be epigenetically switched off.

    Evidence Methylation-specific PCR, bisulfite sequencing, and 5-Aza/TSA pharmacological reactivation in renal carcinoma lines

    PMID:27583477

    Open questions at the time
    • Causal link between methylation and tumor phenotype correlative
    • Methyltransferases responsible not identified
  7. 2019 Medium

    Placed CCND2 downstream of JAK2/STAT3 via direct promoter binding, defining a transcriptional axis sustaining cancer stem cell proliferation.

    Evidence ChIP of STAT3 at the CCND2 promoter plus loss-of-function in patient-derived colorectal cells and xenografts

    PMID:31511084

    Open questions at the time
    • STAT3 cofactors at the promoter not characterized
    • Single tumor type
  8. 2019 Medium

    Established a PRC2/H3K27me3 epigenetic silencing layer at the CCND2 promoter and identified PICOT as a regulator of EED-mediated repression.

    Evidence Reciprocal Co-IP of PICOT with chromatin-resident EED and ChIP for H3K27me3/EED/EZH2 at the CCND2 promoter with knockdown readouts

    PMID:31527584

    Open questions at the time
    • How PICOT modulates PRC2 occupancy mechanistically unresolved
    • Generality beyond T cells untested
  9. 2021 Low

    Resolved the reciprocal brain-growth phenotype by mapping N-terminal loss-of-function variants to microcephaly versus C-terminal gain-of-function variants to megalencephaly.

    Evidence Clinical genetic case series with phenotypic comparison across mutation classes

    PMID:34087052

    Open questions at the time
    • No in vitro functional assays performed to directly confirm loss-of-function
    • Variant-specific protein behavior not measured
  10. 2021 Medium

    Added TGFβ/SMAD3 as a direct transcriptional activator of Ccnd2 in granulosa cell growth, broadening the activating-signal repertoire upstream of CCND2.

    Evidence ChIP-qPCR for SMAD3 at the Ccnd2 promoter with miR-135a 3'UTR targeting analysis

    PMID:34440873

    Open questions at the time
    • SMAD3 cofactor requirements unresolved
    • Single physiological context
  11. 2023 Medium

    Directly connected PI3K/AKT-GSK3β signaling to CCND2 protein stability and Rb phosphorylation, validating the degradation axis pharmacologically.

    Evidence BEZ-235 treatment with western blots of CCND2/GSK3β phosphorylation/Rb and cell cycle analysis in BIA-ALCL cells

    PMID:37647808

    Open questions at the time
    • Direct GSK3β phosphorylation site occupancy on CCND2 not mapped
    • Single cell context
  12. 2023 Medium

    Demonstrated that RNA-binding proteins counteract miRNA repression to stabilize CCND2 mRNA, adding a competitive post-transcriptional control layer.

    Evidence RIP, RNA pull-down, luciferase reporter, and RNA degradation assays for SRSF1 (and ELAVL1/HuR) versus miR-135a/miR-188-5p

    PMID:36280202 PMID:37300687

    Open questions at the time
    • Stabilization mechanism not reconstituted in vitro for HuR
    • Quantitative contribution to physiological CCND2 levels unclear
  13. 2023 High

    Showed cardiomyocyte-restricted CCND2 delivery reactivates the cell cycle in post-mitotic cardiomyocytes and drives myocardial repair across species, establishing therapeutic proliferative reactivation.

    Evidence miRNA-gated modRNA (SMRT) delivery with Ki67/Aurora B staining and functional/histologic readouts in mouse and pig MI models (building on hiPSC-CM overexpression)

    PMID:29018036 PMID:37565345

    Open questions at the time
    • Long-term safety of sustained cardiomyocyte proliferation not addressed
    • CDK partner engagement in cardiomyocytes not characterized
  14. 2025 Medium

    Defined PRC2.1 (MTF2)- rather than PRC2.2 (JARID2)-specific H3K27me3 deposition at the CCND2/CCND1 promoters as opposing G1 progression and modulating CDK4/6 inhibitor sensitivity.

    Evidence Chemogenetic screen, MTF2 vs JARID2 genetic epistasis, genome-wide H3K27me3 ChIP, and palbociclib sensitivity assays

    PMID:39903505

    Open questions at the time
    • How MTF2 selectively targets cyclin D CpG islands not resolved
    • Direct in vivo relevance to therapy resistance untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how the multilayered transcriptional, epigenetic, and post-transcriptional inputs are integrated to set cyclin D2 dosage in a given cell type, and which CDK partners mediate its proliferative output in non-cancer contexts such as cardiomyocytes.
  • No integrated model of competing regulators
  • CDK4/6 engagement assumed but not directly demonstrated in most timeline systems
  • Endogenous GSK-3β phosphorylation kinetics on CCND2 not directly measured

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 3
Localization
GO:0005634 nucleus 2
Pathway
R-HSA-74160 Gene expression (Transcription) 6 R-HSA-1640170 Cell Cycle 5 R-HSA-1643685 Disease 3 R-HSA-8953854 Metabolism of RNA 3
Partners
EEDELAVL1GSK3BRB1SMAD3SRSF1STAT3

Evidence

Reading pass · 20 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 residue (Thr) cause megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome (MPPH). Mutant CCND2 was resistant to proteasomal degradation in vitro compared to wild-type CCND2, leading to protein stabilization. PI3K-AKT pathway activation (via PIK3CA, PIK3R2, or AKT3 mutations) produced similar CCND2 accumulation. In utero electroporation of mutant CCND2 into embryonic mouse brains produced more proliferating progenitors and a smaller fraction exiting the cell cycle, establishing cyclin D2 stabilization as a unifying mechanism in PI3K-AKT-related megalencephaly. In vitro proteasomal degradation assay, patient cell analysis, in utero electroporation, immunoblotting Nature genetics High 24705253
2016 CCND2 mutations in t(8;21) AML cluster around threonine 280 (Thr280). The Thr280Ala-mutated CCND2 leads to increased phosphorylation of the retinoblastoma protein (Rb), causing significant cell cycle changes and increased proliferation in AML cell lines, consistent with a gain-of-function stabilization mechanism. Mutant CCND2 expression in AML cell lines, Rb phosphorylation assay, cell cycle analysis, proliferation assay Leukemia Medium 27843138
2008 RNAi knockdown of CCND2 inhibits proliferation and is progressively cytotoxic in human myeloma cells, demonstrating that myeloma cells are dependent on CCND2 for survival. Kinetin riboside was identified as an inhibitor of CCND2 trans-activation; it upregulated transcription repressor isoforms of CREM and blocked trans-activation of CCND2 by myeloma oncogenes, causing cell-cycle arrest and tumor cell-selective apoptosis. RNAi knockdown, cell-based CCND2 trans-activation screening assay, CREM isoform expression analysis, xenograft mouse model The Journal of clinical investigation High 18431519
2019 STAT3 directly binds the CCND2 promoter to increase CCND2 transcription in colorectal cancer stem cells, placing CCND2 downstream of JAK2/STAT3 signaling. CCND2 expression was required for persistent cancer stem cell growth via maintenance of intact cell cycle progression. Chromatin immunoprecipitation (ChIP) demonstrating STAT3 binding to CCND2 promoter, loss-of-function assays in patient-derived CRC cells and xenografts Journal of experimental & clinical cancer research Medium 31511084
2010 The ETS transcription factor Elf5 directly binds a regulatory segment upstream of the Ccnd2 gene and transcriptionally represses Ccnd2 expression. Loss of Elf5 in mammary epithelial cells and mammary glands leads to upregulation of Ccnd2 with an altered expression pattern in luminal cells. ChIP-cloning to identify Elf5-bound genomic segments, promoter reporter assay, Elf5-null mammary epithelial cell and gland analysis BMC molecular biology Medium 20831799
2019 PICOT (glutaredoxin 3/Grx3) binds chromatin-associated EED (a PRC2 core component) via its PICOT/Grx homology domains. PICOT knockdown reduced H3K27me3 and EED/EZH2 occupancy at the CCND2 gene promoter, resulting in significant increases in CCND2 mRNA and protein in PICOT-deficient T cells, establishing PICOT as a regulator of PRC2-mediated epigenetic silencing of CCND2. Co-immunoprecipitation of PICOT with chromatin-resident EED, ChIP for H3K27me3/EED/EZH2 at CCND2 promoter, PICOT knockdown with CCND2 expression readout Cell death & disease Medium 31527584
2025 PRC2.1 (containing accessory protein MTF2), but not PRC2.2 (containing JARID2), promotes H3K27me3 deposition at CpG islands in the CCND1 and CCND2 promoters to repress their expression and oppose G1 progression. Loss of MTF2 leads to upregulation of both CCND1 and CCND2 and resistance to CDK4/6 inhibitor palbociclib. Chemogenetic screen, genetic epistasis (MTF2 vs JARID2 deletion), H3K27me3 ChIP genome-wide, gene expression analysis, palbociclib sensitivity assay eLife Medium 39903505
2016 Promoter hypermethylation at the CCND2 gene is closely associated with silenced CCND2 expression in renal cell carcinoma. Treatment with demethylating agent 5-Aza (with or without TSA) restored CCND2 expression in methylated RCC cell lines, establishing promoter methylation as a mechanism of CCND2 silencing. Methylation-specific PCR (MSP), bisulfite genomic sequencing (BGS), 5-Aza/TSA pharmacological demethylation, mRNA and protein expression analysis PloS one Medium 27583477
2016 lncRNA linc00598 regulates CCND2 transcription by modulating the transcriptional regulatory effect of FoxO1 on the CCND2 promoter. Knockdown of linc00598 induced G0/G1 cell cycle arrest and inhibited proliferation, placing linc00598 as a positive regulator of CCND2 transcription. Microarray analysis, knockdown experiments, cell cycle analysis, promoter regulation assay involving FoxO1 Scientific reports Low 27572135
2017 Overexpression of CCND2 (cyclin D2) in hiPSC-derived cardiomyocytes activates cell cycle markers (Ki67, Aurora B kinase) 3-7 fold and causes proliferation of these normally post-mitotic cells, resulting in approximately tripled engraftment size and improved myocardial repair in a mouse infarction model compared to wild-type CCND2 hiPSC-CMs. Lentiviral CCND2 overexpression in hiPSC-CMs, cell cycle marker quantification, mouse myocardial infarction model with histological and functional assessments Circulation research Medium 29018036
2023 Cardiomyocyte-specific CCND2 modRNA delivery using a synthetic miRNA-gated system (CCND2-cardiomyocyte SMRTs exploiting miR-1 and miR-208 for cardiomyocyte specificity) activated cell cycle progression markers (Ki67, Aurora B kinase) in post-mitotic cardiomyocytes and significantly promoted cardiomyocyte proliferation, reduced infarct size, and improved cardiac performance in both mouse and pig MI models. Modified mRNA delivery system, cardiomyocyte-specific expression validation, Ki67/Aurora B staining, mouse and pig MI models with functional echocardiography and histology Circulation research High 37565345
2010 MicroRNA let-7a directly binds the 3'UTR of CCND2 mRNA (validated by dual-luciferase reporter assay) and downregulates CCND2 protein expression, causing G1/S cell cycle arrest and inhibiting proliferation in prostate cancer cells. Dual-luciferase reporter assay, western blotting, cell cycle analysis, xenograft model PloS one Medium 20418948
2011 miR-1 directly targets CCND2 (validated by reporter assay) and reduces CCND2 protein to inhibit thyroid carcinoma cell proliferation. An inverse correlation between miR-1 expression and CCND2 protein levels was found in papillary and anaplastic thyroid carcinomas. Luciferase reporter assay, western blot, functional proliferation and migration assays The Journal of clinical endocrinology and metabolism Medium 21752897
2021 CCND2 overexpression activates the MEK/MAPK pathway downstream in breast cancer cells. PRNCR1 lncRNA acts as a ceRNA to sponge miR-377, thereby upregulating CCND2, which in turn activates MEK/MAPK signaling to promote breast cancer growth. Inhibition of the MEK/MAPK pathway with mirdametinib counteracted this effect. Luciferase reporter assay, RNA pull-down, RIP assay, MEK/MAPK pathway protein analysis by western blot, pharmacological inhibition Archives of medical research Low 33608112
2021 ELAVL1 (HuR) stabilizes CCND2 mRNA and counteracts miR-188-5p-mediated suppression of CCND2, establishing ELAVL1 as an RNA-binding protein that competes with miR-188-5p for CCND2 mRNA binding and stabilizes CCND2 transcript in ovarian cancer cells. RIP assay, luciferase reporter assay, rescue experiments with HuR or CCND2 overexpression Cellular and molecular biology Low 37300687
2024 ELAVL1 (HuR) directly binds circ_0002331 and CCND2 mRNA (shown by RIP and RNA pull-down), and circ_0002331 promotes CCND2 mRNA stability by interacting with ELAVL1, establishing a mechanism by which circ_0002331 upregulates CCND2 protein in vascular endothelial cells. RIP assay, RNA pull-down assay, FISH co-localization, western blot for CCND2 protein Cardiovascular toxicology Low 38743320
2021 The granulosa cell TGFBR1-SMAD3 pathway enhances CCND2 promoter activity and upregulates CCND2 expression. ChIP-qPCR demonstrated direct SMAD3 binding at the Ccnd2 promoter, placing CCND2 downstream of TGF-β/SMAD3 signaling in granulosa cell growth during folliculogenesis. ChIP-qPCR for SMAD3 at Ccnd2 promoter, subcellular localization analysis, functional miR-135a targeting of Ccnd2 3'UTR Cells Medium 34440873
2019 SRSF1 competitively binds the 3'UTR region of CCND2 mRNA with miR-135a, suppressing CCND2 mRNA degradation. SRSF1 overexpression increased CCND2 protein levels and promoted ASMC proliferation in asthma, while SRSF1 knockdown reduced CCND2 and inhibited proliferation. RNA immunoprecipitation, RNA pull-down assay, dual-luciferase reporter assay, RNA degradation assay, gain/loss-of-function Pulmonary pharmacology & therapeutics Medium 36280202
2023 PI3K/AKT inhibitor BEZ-235 induces dephosphorylation of GSK3β, which is an activator of CCND2 proteasomal degradation; BEZ-235 treatment reduced CCND2 protein levels, dephosphorylated Rb, and arrested the cell cycle in G1 in BIA-ALCL cells, confirming PI3K/AKT-GSK3β-mediated regulation of CCND2 protein stability. BEZ-235 pharmacological treatment, western blot for CCND2/GSK3β phosphorylation/Rb dephosphorylation, cell cycle analysis Leukemia research Medium 37647808
2021 Proximal (N-terminal region) CCND2 frameshift and stop-gain variants cause microcephaly and simplified cortical gyral pattern, in contrast to distal (C-terminal) CCND2 mutations that cause megalencephaly, suggesting that the two classes of variants produce reciprocal brain growth phenotypes through loss vs. gain of protein function respectively. Clinical genetic analysis, variant characterization, phenotypic comparison across mutation classes (epistatic inference from human genetics) American journal of medical genetics. Part A Low 34087052

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 240 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 131 29018036
2014 De novo CCND2 mutations leading to stabilization of cyclin D2 cause megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome. Nature genetics 123 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
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 95 34609043
2008 Translocations targeting CCND2, CCND3, and MYCN do occur in t(11;14)-negative mantle cell lymphomas. Blood 94 18391076
2019 lncRNA TUG1 Promotes Cisplatin Resistance by Regulating CCND2 via Epigenetically Silencing miR-194-5p in Bladder Cancer. Molecular therapy. Nucleic acids 85 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
2018 CCND2 and CCND3 hijack immunoglobulin light-chain enhancers in cyclin D1- mantle cell lymphoma. Blood 76 30538135
2016 MiR-146a-5p inhibits cell proliferation and cell cycle progression in NSCLC cell lines by targeting CCND1 and CCND2. Oncotarget 76 27494902
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
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 43 34792792
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
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 28 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 24 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
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 23 31629738
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
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 21 33010000
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
2023 LncRNA AC005332.7 Inhibited Ferroptosis to Alleviate Acute Myocardial Infarction Through Regulating miR-331-3p/CCND2 Axis. Korean circulation journal 20 36914604
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 20 29662889
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
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
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
2022 Downregulation of Kcnq1ot1 attenuates β-cell proliferation and insulin secretion via the miR-15b-5p/Ccnd1 and Ccnd2 axis. Acta diabetologica 16 35347427
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
2016 Long noncoding RNA linc00598 regulates CCND2 transcription and modulates the G1 checkpoint. Scientific reports 15 27572135
2022 The MyoD1 Promoted Muscle Differentiation and Generation by Activating CCND2 in Guanling Cattle. Animals : an open access journal from MDPI 14 36230312
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
2021 miR-135a Suppresses Granulosa Cell Growth by Targeting Tgfbr1 and Ccnd2 during Folliculogenesis in Mice. Cells 13 34440873
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
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
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 8 33320844
2019 Severe presentation and complex brain malformations in an individual carrying a CCND2 variant. Molecular genetics & genomic medicine 8 31056854
2023 Ndufa4 Regulates the Proliferation and Apoptosis of Neurons via miR-145a-5p/Homer1/Ccnd2. Molecular neurobiology 7 36763283
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 7 37866807
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
2022 SRSF1 promotes ASMC proliferation in asthma by competitively binding CCND2 with miRNA-135a. Pulmonary pharmacology & therapeutics 6 36280202
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
2025 The PRC2.1 subcomplex opposes G1 progression through regulation of CCND1 and CCND2. eLife 5 39903505
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
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
2024 Circ_0002331 Interacts with ELAVL1 to Improve ox-LDL-Induced Vascular Endothelial Cell Dysfunction via Regulating CCND2 mRNA Stability. Cardiovascular toxicology 4 38743320
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
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

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