ArticleMolecular therapy : the journal of the American Society of Gene Therapy2020
Circular Noncoding RNA NR3C1 Acts as a miR-382-5p Sponge to Protect RPE Functions via Regulating PTEN/AKT/mTOR Signaling Pathway.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 70 citations in OpenAlex.
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- Role and regulation of kinases in age-related macular degeneration.Journal of translational medicine · 2026Review
- Identification of aberrantly expressed circular RNAs in choroidal neovascularization in mice.BMC ophthalmology · 2025Article
- The Role of Non-coding RNAs in Diabetic Retinopathy: Mechanistic Insights and Therapeutic Potential.Molecular neurobiology · 2025Review
- Emerging role of circular RNAs in diabetic retinopathy.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2025Review
- Circular RNA HIPK3 mediates epithelial-mesenchymal transition of retinal pigment epithelial cells by sponging multiple microRNAs.Scientific reports · 2024Article
- Engineering circular RNA for molecular and metabolic reprogramming.Functional & integrative genomics · 2024Review
- Current RNA strategies in treating cardiovascular diseases.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Review
- Insight into the role of non-coding RNA in the diagnosis and treatment of retinitis pigmentosa.Non-coding RNA research · 2024Review
- m6A-Mediated Upregulation of Imprinted in Prader-Willi Syndrome Induces Aberrant Apical-Basal Polarization and Oxidative Damage in RPE Cells.Investigative ophthalmology & visual science · 2024Article
- Circular RNA ZBTB46 depletion alleviates the progression of Atherosclerosis by regulating the ubiquitination and degradation of hnRNPA2B1 via the AKT/mTOR pathway.Immunity & ageing : I & A · 2023Article
- Review
- Differentially expressed circRNAs in peripheral blood samples as potential biomarkers and therapeutic targets for acute angle-closure glaucoma.Scientific reports · 2023Article
- Understanding the roles and regulation patterns of circRNA on its host gene in tumorigenesis and tumor progression.Journal of experimental & clinical cancer research : CR · 2023Review
- CircRNAs in Tumor Radioresistance.Biomolecules · 2022Review
- microRNAs in newborns with low birth weight: relation to birth size and body composition.Pediatric research · 2022Article
- Emerging roles of circular RNAs in retinal diseases.Neural regeneration research · 2022Review
- MiR-382 Functions on the Regulation of Melanogenesis via Targeting dct in Rainbow Trout (Oncorhynchus mykiss).Marine biotechnology (New York, N.Y.) · 2022Article
- Effects of Extracorporeal Shockwave Therapy on Functional Recovery and Circulating miR-375 and miR-382-5p after Subacute and Chronic Spinal Cord Contusion Injury in Rats.Biomedicines · 2022Article
- MicroRNAs as Regulators of Phagocytosis.Cells · 2022Review
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Age-related macular degeneration (AMD) is a universal leading cause for irreversible blindness in the elderly population. Dedifferentiation of retinal pigment epithelium (RPE) cells initiates early pathological events in atrophic AMD. Herein, we aim to investigate effects of a circular RNA derived from the NR3C1 gene (circNR3C1) on regulating RPE function and AMD pathogenesis. circNR3C1 expression was consistently upregulated along with RPE differentiation and was downregulated in dysfunctional RPE and blood serum of AMD patients. Silencing of circNR3C1 reduced RPE characteristic transcripts and proteins, interrupted phagocytosis, accelerated intracellular reactive oxygen species (ROS) generation, and promoted RPE proliferation in vitro. circN3C1 silencing also decreased expressions of RPE characteristic markers and disturbed the ultrastructure of RPE in vivo, as shown by a thickened RPE with twisted basal infoldings and outer segments. Mechanistically, circNR3C1 acted as an endogenous microRNA-382-5p (miR-382-5p) sponge to sequester its activity, which increased phosphatase and tensin homolog on chromosome 10 (PTEN) expression and inhibited the protein kinase B/mammalian target of rapamycin (AKT/mTOR) pathway. miR-382-5p overexpression and PTEN silencing mimicked effects of circNR3C1 silencing on RPE phenotypes in vivo and in vitro. In conclusion, circNR3C1 prevents AMD progression and protects RPE by directly sponging miR-382-5p to block its interaction with PTEN and subsequently blocks the AKT/mTOR pathway. Pharmacological circNR3C1 supplementations are promising therapeutic options for atrophic AMD.
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