ArticleThe Journal of clinical investigation2019
Endothelial miR-30c suppresses tumor growth via inhibition of TGF-β-induced Serpine1.
Article in The Journal of clinical investigation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers, 2 of them syntheses that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
63 citing papers in PubMed, 2 syntheses or guidelines pooled it, 84 citations in OpenAlex.
- MicroRNAs in Tumor Endothelial Cells: Regulation, Function and Therapeutic Applications.Cells · 2023Pooled it
- Effects of AntagomiRs on Different Lung Diseases in Human, Cellular, and Animal Models.International journal of molecular sciences · 2019Pooled it
- Endothelial deletion of the neddylation E2 enzyme UBE2M inhibits tumor growth by promoting nonproductive angiogenesis.The Journal of clinical investigation · 2026Article
- Review
- Identifying Choroidal Neovascularization-Associated Genes with GenePlexus in a Protein-Protein Interaction Network.Life (Basel, Switzerland) · 2026Article
- An epigenetic switch in vascular phenotype augments anti-tumor immunity.Angiogenesis · 2026Article
- Endothelial PDLIM5 promotes tip cell filopodia formation and tumor angiogenesis by regulating ACTN1/ACTN4-dependent actin bundling.Nature communications · 2026Article
- METTL3/m6A-Dependent SERPINE1/VEGFA Axis Mediates Sublethal Heat-Induced Angiogenesis in Hepatocellular Carcinoma.Mediators of inflammation · 2026Article
- Crosstalk between GLTSCR1-deficient endothelial cells and tumour cells promotes colorectal cancer development by activating the Notch pathway.Cell death and differentiation · 2025Article
- Multiomic Landscape of Extracellular Vesicles in Human Carotid Atherosclerotic Plaque Reveals Endothelial Communication Networks.Arteriosclerosis, thrombosis, and vascular biology · 2025Article
- Rescuing ACE2-Deficiency-Mediated Nucleus Pulposus Senescence and Intervertebral Disc Degeneration by a Nanotopology-Enhanced RNAi System.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Exosomes in Skin Flap Survival: Unlocking Their Role in Angiogenesis and Tissue Regeneration.Biomedicines · 2025Review
- Genetically Defined Organoid Models Reveal Mechanisms Driving Squamous Cell Neoplastic Evolution and Identify Potential Therapeutic Vulnerabilities.bioRxiv : the preprint server for biology · 2025Article
- Identifying Mechanism of Resveratrol for the Treatment of COVID-19 and Idiopathic Pulmonary FibrosisCurrent medicinal chemistry · 2025Article
- A Contemporary Review of Plasminogen Activator Inhibitor Type 1: Structure, Function, Genetic Architecture, and Intracellular/Extracellular Roles.TH open : companion journal to thrombosis and haemostasis · 2025Review
- Integration of single-nucleus and exosome RNA sequencing dissected inter-cellular communication and biomarkers in pancreatic ductal adenocarcinoma.Computational and structural biotechnology journal · 2024Article
- High level of circulating cell-free tumor DNA at diagnosis correlates with disease spreading and defines multiple myeloma patients with poor prognosis.Blood cancer journal · 2024Article
- Glial-Cell-Line-Derived Neurotrophic Factor Promotes Glioblastoma Cell Migration and Invasion via the SMAD2/3-SERPINE1-Signaling Axis.International journal of molecular sciences · 2024Article
- Spon1+ inflammatory monocytes promote collagen remodeling and lung cancer metastasis through lipoprotein receptor 8 signaling.JCI insight · 2024Article
- The pathogenesis of cancer-associated thrombosis.International journal of hematology · 2024Review
3 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
15 authors at 7 institutions in 3 countries.
Funding
Abstract
In tumors, extravascular fibrin forms provisional scaffolds for endothelial cell (EC) growth and motility during angiogenesis. We report that fibrin-mediated angiogenesis was inhibited and tumor growth delayed following postnatal deletion of Tgfbr2 in the endothelium of Cdh5-CreERT2 Tgfbr2fl/fl mice (Tgfbr2iECKO mice). ECs from Tgfbr2iECKO mice failed to upregulate the fibrinolysis inhibitor plasminogen activator inhibitor 1 (Serpine1, also known as PAI-1), due in part to uncoupled TGF-β-mediated suppression of miR-30c. Bypassing TGF-β signaling with vascular tropic nanoparticles that deliver miR-30c antagomiRs promoted PAI-1-dependent tumor growth and increased fibrin abundance, whereas miR-30c mimics inhibited tumor growth and promoted vascular-directed fibrinolysis in vivo. Using single-cell RNA-Seq and a NanoString miRNA array, we also found that subtypes of ECs in tumors showed spectrums of Serpine1 and miR-30c expression levels, suggesting functional diversity in ECs at the level of individual cells; indeed, fresh EC isolates from lung and mammary tumor models had differential abilities to degrade fibrin and launch new vessel sprouts, a finding that was linked to their inverse expression patterns of miR-30c and Serpine1 (i.e., miR-30chi Serpine1lo ECs were poorly angiogenic and miR-30clo Serpine1hi ECs were highly angiogenic). Thus, by balancing Serpine1 expression in ECs downstream of TGF-β, miR-30c functions as a tumor suppressor in the tumor microenvironment through its ability to promote fibrin degradation and inhibit blood vessel formation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.