MVP enhances FGF21-induced ferroptosis in hepatocellular carcinoma by increasing lipid peroxidation through regulation of NOX4
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View abstract on PubMed
Summary
This summary is machine-generated.Fibroblast growth factor 21 (FGF21) regulates ferroptosis in hepatocellular carcinoma (HCC) by targeting Major vault protein (MVP). MVP modulates reactive oxygen species (ROS) production, impacting HCC cell death and offering potential therapeutic strategies.
Area Of Science
- Cell Death Mechanisms
- Oncology
- Molecular Biology
Background
- Ferroptosis, an iron-dependent cell death, is induced by reactive oxygen species (ROS) imbalance.
- Inducing ferroptosis is a promising therapeutic strategy for hepatocellular carcinoma (HCC).
- Fibroblast growth factor 21 (FGF21) is a newly identified ferroptosis modulator, but its role in HCC remains unclear.
Purpose Of The Study
- To investigate the role and molecular mechanism of FGF21 in HCC ferroptosis.
- To identify key regulatory proteins involved in FGF21-mediated ferroptosis in HCC.
Main Methods
- Cell culture and molecular biology techniques were used to study HCC cell lines.
- Gene knockdown and overexpression were employed to assess protein function.
- Western blotting, quantitative PCR, and lipid peroxidation assays were performed.
- Xenograft tumor models were utilized for in vivo validation.
Main Results
- Major vault protein (MVP) was identified as a direct target of FGF21 in HCC.
- MVP knockdown reduced lipid peroxidation and ROS production by decreasing NADPH oxidase 4 (NOX4) transcription.
- MVP overexpression increased NOX4 transcription by interfering with IRF1 and YAP1 promoter interaction, enhancing ferroptosis.
- MVP overexpression promoted lipid peroxidation in vivo in xenograft models.
Conclusions
- FGF21 plays a significant role in regulating ferroptosis in HCC.
- MVP is a key mediator of FGF21-induced ferroptosis in HCC, acting via the NOX4 pathway.
- Targeting the FGF21-MVP axis presents a potential therapeutic avenue for HCC treatment.
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