ArticleMolecular therapy : the journal of the American Society of Gene Therapy2023
A protein encoded by circular ZNF609 RNA induces acute kidney injury by activating the AKT/mTOR-autophagy pathway.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 28 papers, 1 of them a synthesis that pooled it.
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28 citing papers in PubMed, 1 synthesis or guideline pooled it, 38 citations in OpenAlex.
- Meta analysis of bioactive compounds, miRNA, siRNA and cell death regulators as sensitizers to doxorubicin induced chemoresistance.Apoptosis : an international journal on programmed cell death · 2022Pooled it
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- Role of circular RNAs in regulating toxicity induced by cancer therapies.Genes & diseases · 2026Review
- Acute kidney injury over the past decade: from definition evolution to pathogenesis insights and innovative therapeutic strategies.Cellular and molecular life sciences : CMLS · 2026Review
- IGF2BP3 promotes progression of head and neck cancers through the circHECTD2/hsa_miR_4310/7157-5p/Smad2 signaling axis in an mMolecular cancer · 2026Article
- Circuitous Ways of EWS::FLI1 Using Circular RNA ZNF609 to Evade Translational Repression by miR-145 in Ewing's Sarcoma.Biomedicines · 2026Article
- Laptm4a mediates renal ischemia-reperfusion injury by regulating the UNC5B-AKT/mTOR signaling pathway.Frontiers in immunology · 2026Article
- Mechanisms of salvianolic acids in kidney disease therapy: advances and perspectives.Frontiers in pharmacology · 2026Review
- Circular RNAs: from transcriptional noise to engineered therapeutics.Frontiers in epigenetics and epigenomics · 2026Review
- Keratin 20 Suppresses Exosomal Secretion of Peroxiredoxin 2 and Ferroptosis in Acute Kidney Injury.Journal of the American Society of Nephrology : JASN · 2026Article
- A multi-omics landscape of programmed cell death in acetaminophen-induced acute kidney injury.Renal failure · 2025Article
- Review
- Circular RNAs in Cardiovascular Physiopathology: From Molecular Mechanisms to Therapeutic Opportunities.International journal of molecular sciences · 2025Review
- Hsa_circ_0026782 Acts as a "Molecular Break" of CREB1-Mediated Transcription by Promoting Its Phosphorylation at Ser142 That Prevents Keloid Progression.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Advances in the research on circular RNA in pediatric pancreatic tumors.Translational pediatrics · 2025Review
- The potential ofJournal of thoracic disease · 2025Article
- NSD1-916aa encoded by CircNSD1 contributes to AKI-to-CKD transition through inducing ferroptosis in tubular epithelial cells.JCI insight · 2025Article
- Functions and application of circRNAs in vascular aging and aging-related vascular diseases.Journal of nanobiotechnology · 2025Review
- A Novel 167-Amino Acid Protein Encoded by CircPCSK6 Inhibits Intrahepatic Cholangiocarcinoma Progression via IKBα Ubiquitination.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Macrophage-mimicking nanotherapy for attenuation of acute pancreatitis.Materials today. Bio · 2025Article
Corrections and comments
- Erratum issued
Authors and funding
15 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Autophagy plays a crucial role in the development and progression of ischemic acute kidney injury (AKI). However, the function and mechanism of circular RNAs (circRNAs) in the regulation of autophagy in ischemic AKI remain unexplored. Herein, we find that circ-ZNF609, originating from the ZNF609 locus, is highly expressed in the kidney after ischemia/reperfusion injury, and urinary circ-ZNF609 is a moderate predictor for AKI in heart disease patients. Overexpression of circ-ZNF609 can activate AKT3/mTOR signaling and induce autophagy flux impairment and cell apoptosis while inhibiting proliferation in HK-2 cells, which is blocked by silencing circ-ZNF609. Mechanistically, circ-ZNF609 encodes a functional protein consisting of 250 amino acids (aa), termed ZNF609-250aa, the overexpression of which can activate AKT3/mTOR signaling and induce autophagy flux impairment and cell apoptosis in HK-2 cells in vitro and in AKI kidneys in vivo. The blockade of AKT and mTOR signaling with pharmacological inhibitors is capable of reversing ZNF609-250aa-induced autophagy flux impairment and cell apoptosis in HK-2 cells. The present study demonstrates that highly expressed circ-ZNF609-encoded ZNF609-250aa induces cell apoptosis and AKI by impairing the autophagy flux via an AKT/mTOR-dependent mechanism. These findings imply that targeting circ-ZNF609 may be a novel therapy for ischemic AKI.
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