ArticleMolecular therapy. Nucleic acids2019
miR-15a/-16 Inhibit Angiogenesis by Targeting the Tie2 Coding Sequence: Therapeutic Potential of a miR-15a/16 Decoy System in Limb Ischemia.
Article in Molecular therapy. Nucleic acids, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 53 citations in OpenAlex.
- Expression of Circulating MicroRNA before and after Abdominal Aneurysm Repair.Journal of vascular research · 2026Article
- Modulation of the Receptor Tyrosine Kinase TIE2/International journal of molecular sciences · 2026Article
- Association of blood miR-15a, miR-146a and miR-200b levels with stages of diabetic retinopathy.Scientific reports · 2025Article
- Differential Expression of Maternal Plasma microRNAs and Their Respective Gene Targets Can Predict Early Fetal Growth Restriction.Life (Basel, Switzerland) · 2025Review
- GelMA@LNP/AST Promotes eNOS-Dependent Angiogenesis Through Autophagy Activation for the Treatment of Hind Limb Ischemia.International journal of nanomedicine · 2025Article
- miRNA-6236 Regulation of Postischemic Skeletal Muscle Angiogenesis.Journal of the American Heart Association · 2024Article
- miR-326 overexpression inhibits colorectal cancer cell growth and proteasome activity by targeting PNO1: unveiling a novel therapeutic intervention strategy.Scientific reports · 2024Article
- Non-coding RNAs as therapeutic targets and biomarkers in ischaemic heart disease.Nature reviews. Cardiology · 2024Review
- Exercise mediates myocardial infarction via non-coding RNAs.Frontiers in cardiovascular medicine · 2024Review
- The Mechanisms of miRNAs on Target Regulation and their Recent Advances in Atherosclerosis.Current medicinal chemistry · 2024Review
- Circulating microRNAs and cardiomyocyte proliferation in heart failure patients related to 10 years survival.ESC heart failure · 2023Article
- Myocardial angiogenesis induced by concurrent vitamin D supplementation and aerobic-resistance training is mediated by inhibiting miRNA-15a, and miRNA-146a and upregulating VEGF/PI3K/eNOS signaling pathway.Pflugers Archiv : European journal of physiology · 2023Article
- Pattern of tamoxifen-induced Tie2 deletion in endothelial cells in mature blood vessels using endo SCL-Cre-ERT transgenic mice.PloS one · 2022Article
- Therapeutic angiogenesis-based strategy for peripheral artery disease.Theranostics · 2022Review
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- A Comprehensive miRNome Analysis of Macrophages Isolated from db/db Mice and Selected miRNAs Involved in Metabolic Syndrome-Associated Cardiac Remodeling.International journal of molecular sciences · 2021Article
- Control of Gene Expression by Exosome-Derived Non-Coding RNAs in Cancer Angiogenesis and Lymphangiogenesis.Biomolecules · 2021Review
- MiRNAs in Gestational Diabetes Mellitus: Potential Mechanisms and Clinical Applications.Journal of diabetes research · 2021Review
- Circulating miRNA Spaceflight Signature Reveals Targets for Countermeasure Development.Cell reports · 2020Article
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Authors and funding
14 authors at 3 institutions in 2 countries.
Funding
Abstract
MicroRNA-15a (miR-15a) and miR-16, which are transcribed from the miR-15a/miR-16-1 cluster, inhibit post-ischemic angiogenesis. MicroRNA (miRNA) binding to mRNA coding sequences (CDSs) is a newly emerging mechanism of gene expression regulation. We aimed to (1) identify new mediators of the anti-angiogenic action of miR-15a and -16, (2) develop an adenovirus (Ad)-based miR-15a/16 decoy system carrying a luciferase reporter (Luc) to both sense and inhibit miR-15a/16 activity, and (3) investigate Ad.Luc-Decoy-15a/16 therapeutic potential in a mouse limb ischemia (LI) model. LI increased miR-15a and -16 expression in mouse muscular endothelial cells (ECs). The miRNAs also increased in cultured human umbilical vein ECs (HUVECs) exposed to serum starvation, but not hypoxia. Using bioinformatic tools and luciferase activity assays, we characterized miR-15a and -16 binding to Tie2 CDS. In HUVECs, miR-15a or -16 overexpression reduced Tie2 at the protein, but not the mRNA, level. Conversely, miR-15a or -16 inhibition improved angiogenesis in a Tie2-dependent manner. Local Ad.Luc-Decoy-15a/16 delivery increased Tie2 levels in ischemic skeletal muscle and improved post-LI angiogenesis and perfusion recovery, with reduced toe necrosis. Bioluminescent imaging (in vivo imaging system [IVIS]) provided evidence that the Ad.Luc-Decoy-15a/16 system responds to miR-15a/16 increases. In conclusion, we have provided novel mechanistic evidence of the therapeutic potential of local miR-15a/16 inhibition in LI.
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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.