ArticleAntioxidants & redox signaling2014
Hypoxia-responsive microRNA-101 promotes angiogenesis via heme oxygenase-1/vascular endothelial growth factor axis by targeting cullin 3.
Article in Antioxidants & redox signaling, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers, 1 of them a synthesis that pooled it.
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Who cites it
44 citing papers in PubMed, 1 synthesis or guideline pooled it, 88 citations in OpenAlex.
- Medical Gas Therapy for Tissue, Organ, and CNS Protection: A Systematic Review of Effects, Mechanisms, and Challenges.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Pooled it
- The role of salvianolic acid B and benzoylpaeoniflorin in enhancing angiogenesis through Nrf2/HO-1/VEGFA signaling axis in ischemic stroke recovery.Pharmaceutical biology · 2026Article
- Adaptive Significance of Non-coding RNAs: Insights from Cancer Biology.Molecular biology and evolution · 2025Review
- Hypoxia-Induced miR-101 Impairs Endothelial Barrier Integrity Through Altering VE-Cadherin and Claudin-5.Molecular neurobiology · 2024Article
- Diagnostic Role of Cell-Free miRNAs in Identifying Placenta Accreta Spectrum during First-Trimester Screening.International journal of molecular sciences · 2024Article
- Flow-induced reprogramming of endothelial cells in atherosclerosis.Nature reviews. Cardiology · 2023Review
- Altered MicroRNA Maturation in Ischemic Hearts: Implication of Hypoxia on XPO5 and DICER1 Dysregulation and RedoximiR State.Antioxidants (Basel, Switzerland) · 2023Article
- Review
- Regulatory pathways and drugs associated with ferroptosis in tumors.Cell death & disease · 2022Review
- The intricacies of NRF2 regulation in cancer.Seminars in cancer biology · 2021Review
- CNKSR1 serves as a scaffold to activate an EGFR phosphatase via exclusive interaction with RhoB-GTP.Life science alliance · 2021Article
- An Analysis of the Multifaceted Roles of Heme in the Pathogenesis of Cancer and Related Diseases.Cancers · 2021Review
- Pharmacological Targeting of Heme Oxygenase-1 in Osteoarthritis.Antioxidants (Basel, Switzerland) · 2021Review
- Review
- MicroRNA-210-3p is transcriptionally upregulated by hypoxia induction and thus promoting EMT and chemoresistance in glioma cells.PloS one · 2021Article
- Positive and Negative Regulation of Ferroptosis and Its Role in Maintaining Metabolic and Redox Homeostasis.Oxidative medicine and cellular longevity · 2021Review
- Protective Role of Nrf2 in Renal Disease.Antioxidants (Basel, Switzerland) · 2020Review
- Inhibition of miR-155 Attenuates Detrimental Vascular Effects of Tobacco Cigarette Smoking.Journal of the American Heart Association · 2020Article
- The pro-migration and anti-apoptosis effects of HMGA2 in HUVECs stimulated by hypoxia.Cell cycle (Georgetown, Tex.) · 2020Article
- Role of the KEAP1-NRF2 Axis in Renal Cell Carcinoma.Cancers · 2020Review
Corrections and comments
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Authors and funding
13 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimsHypoxia induces expression of various genes and microRNAs (miRs) that regulate angiogenesis and vascular function. In this study, we investigated a new functional role of new hypoxia-responsive miR-101 in angiogenesis and its underlying mechanism for regulating heme oxygenase-1 (HO-1) and vascular endothelial growth factor (VEGF) expression.
resultsWe found that hypoxia induced miR-101, which binds to the 3'untranslated region of cullin 3 (Cul3) and stabilizes nuclear factor erythroid-derived 2-related factor 2 (Nrf2) via inhibition of the proteasomal degradation pathway. miR-101 overexpression promoted Nrf2 nuclear accumulation, which was accompanied with increases in HO-1 induction, VEGF expression, and endothelial nitric oxide synthase (eNOS)-derived nitric oxide (NO) production. The elevated NO-induced S-nitrosylation of Kelch-like ECH-associated protein 1 and subsequent induction of Nrf2-dependent HO-1 lead to further elevation of VEGF production via a positive feedback loop between the Nrf2/HO-1 and VEGF/eNOS axes. Moreover, miR-101 promoted angiogenic signals and angiogenesis both in vitro and in vivo, and these events were attenuated by inhibiting the biological activity of HO-1, VEGF, or eNOS. Moreover, these effects were also observed in aortic rings from HO-1(+/-) and eNOS(-/-) mice. Local overexpression of miR-101 improved therapeutic angiogenesis and perfusion recovery in the ischemic mouse hindlimb, whereas antagomiR-101 diminished regional blood flow. INNOVATION: Hypoxia-responsive miR-101 stimulates angiogenesis by activating the HO-1/VEGF/eNOS axis via Cul3 targeting. Thus, miR-101 is a novel angiomir.
conclusionOur results provide new mechanistic insights into a functional role of miR-101 as a potential therapeutic target in angiogenesis and vascular remodeling.
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