Affinage

DNM3

Dynamin-3 · UniProt Q9UQ16

Length
869 aa
Mass
97.7 kDa
Annotated
2026-06-09
21 papers in source corpus 8 papers cited in narrative 8 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 4/5 claims corpus-supported (80%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

DNM3 functions as a growth-suppressive gene across several carcinoma contexts, where restoring its expression curtails proliferation, migration, and invasion and engages programmed cell death (PMID:31572010, PMID:31388312, PMID:30349300). In hepatocellular carcinoma its anti-proliferative action coincides with G0/G1 arrest, apoptosis, and elevated p53 protein (PMID:26784388), while in colon cancer DNM3 induces mitochondrial apoptosis, reduces MMP-2/MMP-9 expression and gelatinase activity, and lowers AKT pathway signaling (PMID:31388312, PMID:30349300). This tumor-suppressive output is held down by oncogenic non-coding RNAs: miR-221 binds the DNM3 3'UTR to silence its protein in glioma and promote temozolomide resistance (PMID:27837435), and miR-376c-3p directly targets DNM3 as the effector arm of a linc01278/miR-376c-3p axis in papillary thyroid carcinoma (PMID:31572010). Beyond cancer, DNM3 binds neuronal nitric oxide synthase (nNOS) in the renal medulla and acts as a negative regulator of NO synthesis downstream of FXR, with FXR activation suppressing DNM3 to permit increased NO production (PMID:35792095). DNM3 localization is also perturbed in LRRK2 Gly2019Ser neurons, where it behaves as a population-specific modifier of parkinsonism age of onset (PMID:27692902).

Mechanistic history

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

    Establishing that DNM3 is silenced by an oncogenic microRNA defined how its loss is achieved in tumors rather than merely correlated with them.

    Evidence Dual-luciferase reporter and western blot with exosomal miR-221 transfer in glioma cells

    PMID:27837435

    Open questions at the time
    • Does not establish DNM3's downstream effector mechanism in glioma
    • miR-221 has many targets; DNM3-specific contribution to temozolomide resistance not isolated
  2. 2016 Low

    Gain-of-function showed DNM3 restraint of hepatocellular carcinoma growth, linking it to cell-cycle arrest and p53.

    Evidence Overexpression with proliferation, colony, cell-cycle/apoptosis flow cytometry and p53 western blot in HCC cells

    PMID:26784388

    Open questions at the time
    • p53 placement inferred from protein level without direct epistasis
    • Overexpression only; no loss-of-function confirmation
  3. 2016 Low

    A genetic-modifier study connected DNM3 to neuronal biology, showing altered localization in LRRK2-mutant neurons and genotype-dependent striatal expression.

    Evidence Immunofluorescence in murine LRRK2 G2019S cortical neurons and genotype-correlated expression in human striatum

    PMID:27692902

    Open questions at the time
    • No direct functional manipulation of DNM3 in neurons
    • Mechanism linking localization change to age of onset unresolved
  4. 2018 Low

    DNM3 was tied to extracellular matrix remodeling by showing it downregulates MMP-2/MMP-9 while suppressing colon cancer invasion.

    Evidence Stable overexpression with transwell migration/invasion assays and MMP-2/MMP-9 western blot in SW620/LoVo cells

    PMID:30349300

    Open questions at the time
    • MMP regulation not mechanistically dissected
    • Single overexpression approach without knockdown
  5. 2019 Medium

    A rescue experiment positioned DNM3 as the functional effector of a lincRNA/miRNA axis, moving it from a target to a pathway node.

    Evidence Dual-luciferase reporter plus DNM3 overexpression rescue of miR-376c-3p mimic in papillary thyroid carcinoma cells

    PMID:31572010

    Open questions at the time
    • Downstream effectors of DNM3 in thyroid carcinoma not identified
    • Single-lab finding
  6. 2019 Low

    Mechanistic placement extended to AKT signaling and mitochondrial apoptosis, broadening DNM3's tumor-suppressive output in colon cancer.

    Evidence Overexpression with CCK-8/colony assays, transwell, gelatin zymography, Annexin V/PI flow cytometry, and AKT western blot

    PMID:31388312

    Open questions at the time
    • AKT epistasis not confirmed by direct pathway manipulation
    • Overexpression system only
  7. 2022 Medium

    A physical DNM3-nNOS interaction defined a non-cancer role for DNM3 as a negative regulator of NO synthesis under FXR control.

    Evidence DNM3-nNOS binding assay with FXR agonist/knockdown in mIMCD-K2 cells and NO measurement in vitro and in HFS mouse model

    PMID:35792095

    Open questions at the time
    • Reciprocal validation and binding interface not characterized
    • How DNM3 mechanistically restrains nNOS activity unresolved
  8. 2025 Low

    Epigenetic regulation of the DNM3 promoter was linked to peripheral nerve repair via DNM3-AKT signaling, extending the AKT axis beyond cancer.

    Evidence Sciatic nerve crush rat model with folic acid treatment, promoter DNA methylation/histone analyses, functional and apoptosis/autophagy/oxidative-stress readouts

    PMID:40163256

    Open questions at the time
    • DNM3 pathway placement inferred from pharmacological treatment without DNM3 loss-of-function rescue
    • Direct DNM3-AKT mechanism in Schwann cells not isolated

Open questions

Synthesis pass · forward-looking unresolved questions
  • The molecular activity of DNM3 as a GTPase and its direct mechanistic link to the downstream pathways (p53, AKT, MMP regulation, nNOS) it modulates remain undefined.
  • No enzymatic or structural characterization in the corpus
  • Epistasis between DNM3 and AKT/p53 unestablished
  • No loss-of-function in vivo demonstration of tumor suppression

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Partners
NOS1

Evidence

Reading pass · 8 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2016 DNM3 is a direct target of miR-221; dual-luciferase reporter assay confirmed that miR-221 binds the DNM3 3'UTR, and exosomal miR-221 suppresses DNM3 protein expression in glioma cells, promoting tumor progression and temozolomide resistance. Dual-luciferase reporter assay, western blotting, exosome treatment of SHG-44 cells, anti-miR-221 transfection Journal of neuro-oncology Medium 27837435
2016 DNM3 overexpression in hepatocellular carcinoma cells reduces proliferation, induces G0/G1 arrest, and stimulates apoptosis; the anti-proliferative effect is associated with upregulation of p53 protein. Proliferation assay, colony formation assay, flow cytometry (cell cycle and apoptosis), western blotting for p53 Medical science monitor Low 26784388
2019 DNM3 is a direct target of miR-376c-3p; dual-luciferase reporter assay confirmed the interaction, and DNM3 overexpression abolished the pro-tumorigenic effects of miR-376c-3p mimic in papillary thyroid carcinoma cells, establishing DNM3 as a downstream effector of the linc01278/miR-376c-3p axis. Dual-luciferase reporter assay, miR-376c-3p mimic/inhibitor transfection, DNM3 overexpression rescue experiment, proliferation/apoptosis/migration assays Cancer management and research Medium 31572010
2019 DNM3 overexpression in colon cancer cells inhibits proliferation, induces mitochondrial apoptosis, suppresses migration and invasion, and reduces MMP9 proteolytic activity; mechanistically, DNM3 overexpression inhibits the AKT signaling pathway. CCK-8 and colony formation assays, transwell invasion/migration assays, gelatin zymography (MMP9 activity), Annexin V/PI flow cytometry, western blotting Cancer management and research Low 31388312
2018 DNM3 overexpression in colon cancer cells (SW620 and LoVo) inhibits proliferation, migration, and invasion, and downregulates MMP-2 and MMP-9 protein expression. Stable overexpression vector (PCDH-CMV-MCS-EF1a-GFP-Puro-DNM3), cell proliferation assay, transwell migration/invasion assay, western blot for MMP-2 and MMP-9 OncoTargets and therapy Low 30349300
2022 In renal collecting duct cells, DNM3 binds neuronal nitric oxide synthase (nNOS) in the renal medulla; FXR activation suppresses DNM3 expression, and DNM3 deficiency elevates NO production, placing DNM3 as a negative regulator of nNOS-dependent NO synthesis downstream of FXR. Co-immunoprecipitation/binding assay (DNM3–nNOS interaction stated), FXR agonist/knockdown in mIMCD-K2 cells, NO production measurements in vitro and in vivo (HFS mouse model), renal fxr overexpression in mice Journal of hypertension Medium 35792095
2016 Dynamin-3 localization is perturbed in murine LRRK2 Gly2019Ser cortical neurons, and DNM3 expression in human striatum varies as a function of the rs2421947 genotype, suggesting that DNM3 acts as a modifier of LRRK2 Gly2019Ser parkinsonism age of onset. Immunofluorescence localization in primary murine LRRK2 G2019S cortical neurons; gene expression analysis in human striatal tissue correlated with genotype The Lancet. Neurology Low 27692902
2025 Folic acid modulates DNM3 gene expression through epigenetic mechanisms (DNA methylation and histone modifications of the DNM3 promoter) in Schwann cells and neurons, and promotes peripheral nerve repair via the DNM3-AKT signaling pathway, regulating apoptosis, autophagy, and oxidative stress. Sciatic nerve crush injury rat model, CCK-8 assay, flow cytometry, balance beam test, electromyography, ELISA, epigenetic analyses (DNA methylation/histone modification of DNM3 promoter), HPLC-MS metabolite quantification Neuromolecular medicine Low 40163256

Source papers

Stage 0 corpus · 21 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2016 Exosomal miR-221 targets DNM3 to induce tumor progression and temozolomide resistance in glioma. Journal of neuro-oncology 103 27837435
2007 Sézary syndrome is a unique cutaneous T-cell lymphoma as identified by an expanded gene signature including diagnostic marker molecules CDO1 and DNM3. Leukemia 83 18033314
2016 DNM3 and genetic modifiers of age of onset in LRRK2 Gly2019Ser parkinsonism: a genome-wide linkage and association study. The Lancet. Neurology 67 27692902
2005 A conserved noncoding intronic transcript at the mouse Dnm3 locus. Genomics 65 15885504
2017 DNM3, p65 and p53 from exosomes represent potential clinical diagnosis markers for glioblastoma multiforme. Therapeutic advances in medical oncology 32 29449895
2019 Linc01278 inhibits the development of papillary thyroid carcinoma by regulating miR-376c-3p/DNM3 axis. Cancer management and research 27 31572010
2016 DNM3 Attenuates Hepatocellular Carcinoma Growth by Activating P53. Medical science monitor : international medical journal of experimental and clinical research 27 26784388
2018 α-synuclein (SNCA) but not dynamin 3 (DNM3) influences age at onset of leucine-rich repeat kinase 2 (LRRK2) Parkinson's disease in Spain. Movement disorders : official journal of the Movement Disorder Society 25 29473656
2020 Analysis of DNM3 and VAMP4 as genetic modifiers of LRRK2 Parkinson's disease. Neurobiology of aging 22 32873436
2019 siPRDX2-elevated DNM3 inhibits the proliferation and metastasis of colon cancer cells via AKT signaling pathway. Cancer management and research 18 31388312
2022 Renal Farnesoid X Receptor improves high fructose-induced salt-sensitive hypertension in mice by inhibiting DNM3 to promote nitro oxide production. Journal of hypertension 11 35792095
2014 Classical dynamin DNM1 and DNM3 genes attain maximum expression in the normal human central nervous system. BMC research notes 11 24673776
2019 SNCA but not DNM3 and GAK modifies age at onset of LRRK2-related Parkinson's disease in Chinese population. Journal of neurology 8 31041581
2025 Folic Acid Promotes Peripheral Nerve Injury Repair via Regulating DNM3-AKT Pathway Through Mediating Methionine Cycle Metabolism. Neuromolecular medicine 7 40163256
2024 Osteoporosis GWAS-implicated DNM3 locus contextually regulates osteoblastic and chondrogenic fate of mesenchymal stem/progenitor cells through oscillating miR-199a-5p levels. JBMR plus 7 38686038
2024 Discovery of Novel TULP4/ACTN4/EWSR1/ACTB::MYB and ESRRG::DNM3 Fusions Expands Molecular Landscape of Adenoid Cystic Carcinoma Beyond Fusions Between MYB/MYBL1 and NFIB Genes. The American journal of surgical pathology 6 39235305
2018 Construction of a recombinant eukaryotic expression vector containing DNM3 gene and its expression in colon cancer cells. OncoTargets and therapy 6 30349300
2018 No association of DNM3 with age of onset in Asian Parkinson's disease. European journal of neurology 3 30133089
2018 No evidence for DNM3 as genetic modifier of age at onset in idiopathic Parkinson's disease. Neurobiology of aging 2 30340792
2022 Expression of DNM3 is associated with good outcome in colorectal cancer. Open medicine (Warsaw, Poland) 1 35178475
2021 TBX15 rs98422, DNM3 rs1011731, RAD51B rs8017304, and rs2588809 Gene Polymorphisms and Associations With Pituitary Adenoma. In vivo (Athens, Greece) 1 33622874

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