Competitive adsorption of microRNA-532-3p by circular RNA SOD2 activates Thioredoxin Interacting Protein/NLR family pyrin domain containing 3 pathway and promotes pyroptosis of non-alcoholic fatty hepatocytes
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View abstract on PubMed
Summary
This summary is machine-generated.Circular RNA SOD2 (circSOD2) promotes non-alcoholic fatty liver disease (NAFLD) by activating the TXNIP/NLRP3 inflammasome pathway. Targeting circSOD2 may offer a therapeutic strategy for NAFLD by reducing pyroptosis and inflammation.
Area Of Science
- Hepatology
- Molecular Biology
- Cell Death Mechanisms
Background
- Pyroptosis, a programmed cell death, exacerbates inflammation and fibrosis in non-alcoholic fatty liver disease (NAFLD).
- Circular RNAs (circRNAs) are emerging regulators in NAFLD pathogenesis, influencing cell pyroptosis.
Purpose Of The Study
- To investigate the roles and underlying mechanisms of circRNAs in NAFLD.
- To identify specific circRNAs involved in NAFLD-associated pyroptosis.
Main Methods
- Established high-fat diet (HFD)-induced rat and palmitic acid (PA)-treated hepatocyte models.
- Identified circSOD2 using the circMine database.
- Assessed gene/protein expression, inflammatory markers, pyroptosis, and lipid deposition.
- Validated molecular interactions using dual-luciferase reporter and RNA immunoprecipitation assays.
Main Results
- Upregulation of circSOD2 and TXNIP, with downregulation of miR-532-3p observed in NAFLD models.
- miR-532-3p targets TXNIP, inhibiting the TXNIP/NLRP3 inflammasome pathway.
- circSOD2 sponges miR-532-3p, activating the TXNIP/NLRP3 pathway and promoting pyroptosis.
- Knockdown of circSOD2 or TXNIP ameliorated pyroptosis; circSOD2 knockdown mitigated NAFLD progression in vivo.
Conclusions
- circSOD2 acts as a molecular sponge for miR-532-3p, thereby activating the TXNIP/NLRP3 inflammasome pathway.
- This activation promotes pyroptosis, contributing to the pathogenesis of NAFLD.
- circSOD2 represents a potential therapeutic target for NAFLD.
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