ArticleArchives of toxicology2026
piR-16404 drives ferroptotic liver injury via CASTOR1/mTORC1/GPX4 dysregulation in HepG2 cells and mice: a novel toxicity mechanism of N, N-dimethylformamide.
Article in Archives of toxicology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed.
- Ellagic Acid Enhances RSL3-Induced Ferroptosis by Inhibiting the Nrf2/HO-1 Signaling Pathway in Pancreatic Ductal Adenocarcinoma.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- miR-885-3p promotes hepatocellular carcinoma metastasis by targeting TASP1 to stabilize HIF-1α and activate hypoxia-driven angiogenic and invasive programs.Molecular biology reports · 2026Article
- The Potentials of Stem Cell-Derived Exosomal MicroRNAs in Ferroptosis Modulation: Molecular Insights into Hepatoprotection, Neuroprotection, Cardioprotection, Renoprotection and Pulmonoprotection.Stem cell reviews and reports · 2026Review
- The power of phytochemicals in cancer chemoprevention through multi-target modulation of oncogenic signaling pathways.Discover oncology · 2026Review
- FERPIR promotes cardiomyocyte survival and attenuates cardiac remodeling after myocardial infarction.Cell death & disease · 2026Article
- Single-nucleus RNA sequencing reveals ferroptosis as a potential contributor to the pathogenesis of focal cortical dysplasia.Clinical and translational medicine · 2026Article
- Beyond silencing: integrative multi-omics and spatial profiling unravel the systems-level role of piRNAs in HBV-driven Hepatocarcinogenesis.Molecular biology reports · 2026Review
- piR-27222 alleviates dexamethasone-induced osteoporosis by inhibiting ferroptosis through modulating WWP1.Journal of orthopaedic surgery and research · 2026Article
- Gallic acid antagonizes deoxynivalenol toxicity by inhibiting DON-induced ferroptosis.NPJ science of food · 2026Article
- Protective Effect and Mechanism of Rosiglitazone in α-amanitin-induced Hepatotoxicity Via Activation of PPAR-γ/Nrf2 Signaling Pathway.Journal of biochemical and molecular toxicology · 2026Article
- Yin-Dan-Ping-Gan Capsule Mitigates CCLPharmaceuticals (Basel, Switzerland) · 2026Article
- Targeting glutathione peroxidase 4 in ferroptosis: from immune regulation to pharmacological development and translational applications.Frontiers in pharmacology · 2026Review
- Bioengineering Strategies to Address Key Bottlenecks in Ferroptosis-Based Cancer Therapy: A Critical Review.International journal of nanomedicine · 2026Review
- Coq4 deficiency induces placental vascular development defects through FSP1/CoQ10 axis-mediated endothelial ferroptosis.Frontiers in cell and developmental biology · 2026Article
- Exploring the Potential Role of Manganese-Based Zeolitic Imidazolate Framework Nanoparticles in Cancer Therapy:International journal of nanomedicine · 2026Article
- The Natural Compound Cornuside Protects Against Acute Liver Failure Induced by Lipopolysaccharide and D-Galactosamine.Drug design, development and therapy · 2026Article
- Long noncoding RNA X-inactive-specific transcript promotes hepatic fibrosis by suppressing ferroptosis in hepatic stellate cells via the miR-663a/GPX4 axis.Frontiers in physiology · 2025Article
Corrections and comments
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Authors and funding
6 authors.
Funding
Abstract
N, N-dimethylformamide (DMF), a widely used industrial solvent including new energy technologies, induces hepatotoxicity through poorly understood mechanisms. This study demonstrates that DMF exposure triggers ferroptosis in hepatocytes, characterized by glutathione depletion, iron accumulation, and lipid peroxidation both in vitro (0-160 mM DMF exposure) and in vivo (0, 750 mg/kg and 1500 mg/kg of DMF exposure). Transmission electron microscopy revealed ferroptotic mitochondrial damage, while biochemical assays confirmed GPX4 suppression and elevated 4-HNE levels. piRNA sequencing identified piR-16404 as significantly downregulated following DMF exposure. Functional studies showed piR-16404 overexpression attenuated DMF-induced ferroptosis by targeting CASTOR1, an arginine sensor for mTORC1. Mechanistically, piR-16404 binds CASTOR1's 3'-UTR to promote its degradation, thereby reactivating mTORC1-GPX4 signaling. In vivo supplementation of agomir-piR-16404 ameliorated DMF-induced liver injury, reducing serum ALT/AST by 42-58% and restoring hepatic GPX4 expression. Our findings establish ferroptosis as a key pathway in DMF hepatotoxicity and identify the piR-16404-CASTOR1-mTORC1 axis as a novel therapeutic target, providing new insights into environmental chemical-induced liver injury mechanisms.
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Registered trials
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