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Cited by 66Circular RNAs in diseasesRetinal Diseases and TreatmentsRetinal Development and Disorders

Circular Noncoding RNA NR3C1 Acts as a miR-382-5p Sponge to Protect RPE Functions via Regulating PTEN/AKT/mTOR Signaling Pathway

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Chen, Xue, Jiang, Chao, Sun, Ruxu, Yang, Daidi, Liu, Qinghuai·2020·Molecular Therapy
DOI 10.1016/j.ymthe.2020.01.010PMC PMC7054734
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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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  • Upregulation of miR-382-5p may contribute to AMD pathogenesis by promoting dedifferentiation, proliferation, and ROS production while impairing phagocytosis, and miR-382-5p is regulated by circNR3C1.

    “Similarly, upregulation of miR-382-5p may contribute to pathogenesis of AMD through promotion of dedifferentiation, proliferation, and reactive oxygen species production, whereas phagocytosis is impaired. This microRNA is regulated by circNR3C1, which acts as an endogenous sponge [273].”

    From MicroRNAs as Regulators of Phagocytosis (2022) · cites this paper as [273]

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Cited by

Sorted by citations

Authors
Chen, X., Jiang, C., Sun, R., Yang, D., & Liu, Q.
Affiliations
Jiangsu Province Hospital (CN)
Corresponding author
Liu, Qinghuai
ORCID
Venue
Molecular Therapy
Publisher
Elsevier BV
Published
2020-03
Volume
28
Issue
3
Pages
929-945
ISSN
1525-0016 (ISSN-L)
DOI
10.1016/j.ymthe.2020.01.010
PMC
PMC7054734
OpenAlex
W2999733319
Cited by
66
References
6
Citations by year
2026: 7 · 2025: 5 · 2024: 12 · 2023: 14 · 2022: 15 · 2021: 10 · 2020: 3
FWCI
3.41
Type
journal article
Language
en
Open access
Licence
Locations
  • Molecular Therapy (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Six Talent Peaks Project in Jiangsu Province (WSW-004)
  • National Key Research and Development Program of China (2017YFA0104100)
  • Natural Science Foundation of Jiangsu Province (BK20171087)
  • National Natural Science Foundation of China (81770973, 81700877)
  • Priority Academic Program Development of Jiangsu Higher Education Institutions
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Circular RNAs in diseases
  • Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinal Development and Disorders
Keywords
circular RNA, miR-382-5p, microRNA sponge, retinal pigment epithelium, dry age-related macular degeneration, PTEN, Akt/mTOR signaling, phagocytosis, reactive oxygen species
MeSH terms
RNA, Circular, Fluorescent Antibody Technique, Gene Expression Regulation, Humans, Macular Degeneration, Receptors, Glucocorticoid, Signal Transduction, RNA, Untranslated, RNA Interference, MicroRNAs, Proto-Oncogene Proteins c-akt, PTEN Phosphohydrolase, Retinal Pigment Epithelium, TOR Serine-Threonine Kinases

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