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Ferroptosis is an iron-dependent form of oxidative cell death. Competitive endogenous RNAs diminish the inhibitory impact of microRNAs on other transcripts by chelating effects, which affects ferroptosis and reactive oxygen species (ROS) levels. However, the role of ferroptosis in excessive copper (Cu)-induced renal injury via the ceRNA axis has not been fully illustrated yet. Herein, we found that Cu induced ferroptosis in duck renal tubular epithelial cells, as indicated by the increase in intracellular iron levels and lipid peroxidation, upregulation of PTGS2 and ACSL4 levels, reduced GPX4 and GSH levels. In addition, knockdown miR-novel-100 could effectively decreased ferroptosis induced by Cu. Overexpression of miR-novel-100 or TC2N knockdown resulted in the stimulation of ROS and the upregulation of ferroptosis indicators. However, butylated hydroxyanisole (BHA) decreased the stimulation of ROS and the ferroptosis effect caused by miR-novel-100 overexpression. In conclusion, Cu induced ferroptosis by activating the lncRNA-TCONS-6251/miR-novel-100/TC2N axis to cause ROS accumulation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Aims: Insulin-like growth factor binding protein-related protein 1 (IGFBPrP1) promotes hepatic stellate cell (HSC) autophagy and activation. However, the underlying mechanism remains unknown. Noncoding RNAs (ncRNAs) including long noncoding RNAs (lncRNAs) and microRNAs (miRNAs), have received increasing attention. We aimed to investigate the roles of the lncRNA nuclear enriched abundant transcript 1 (NEAT1), miR-29b, and autophagy related protein 9a (Atg9a), and their relationships with each other during IGFBPrP1-induced HSC autophagy and activation., Main Methods: Levels of NEAT1, miR-29b, Atg9a, and autophagy were detected in adenovirus-mediated IGFBPrP1 (AdIGFBPrP1)-treated mouse liver tissue and immortalized mouse hepatic stellate cell line JS1 transfected with either AdIGFBPrP1 or siIGFBPrP1. In AdIGFBPrP1-treated JS1 cells, autophagy and activation were detected after altering NEAT1, miR-29b, or Atg9a levels. In AdIGFBPrP1-treated JS1 cells, relationships among NEAT1, miR-29b, and Atg9a were explored using dual-luciferase reporter assays, Western blot, qRT-PCR, and immunofluorescence., Key Findings: IGFBPrP1 increased levels of NEAT1, Atg9a, and autophagy while decreasing the level of miR-29b in mouse liver tissues and mouse HSCs. Moreover, NEAT1 increased HSC autophagy and activation while miR-29b decreased both processes. Atg9a also participated in IGFBPrP1-induced HSC autophagy and activation. Importantly, NEAT1, miR-29b, and Atg9a formed a NEAT1/miR-29b/Atg9a regulatory axis for IGFBPrP1-induced HSC autophagy and activation., Significance: Our study unveiled the new NEAT1/miR-29b/Atg9a regulatory axis involved in IGFBPrP1-induced mouse HSC autophagy and activation. The study thus provides new insights in the pathogenesis and potential therapeutic strategies of liver fibrosis., (Copyright © 2019 Elsevier Inc. All rights reserved.)