| Expression pattern: |
UP |
| Associated gene: |
HuR, EZH2 mRNA, STAT1 mRNA, FOXK1 mRNA |
| Associated microRNA: |
- |
| Biological function: |
circFOXP1 promotes pulmonary fibrosis and counteracts the anti-fibrotic effects of MMF; downregulation of circFOXP1 promotes autophagy and suppresses ferroptosis. |
| Molecular mechanism: |
circFOXP1 binds HuR and promotes HuR expression, stability, and nucleocytoplasmic translocation; the circFOXP1-HuR axis stabilizes EZH2, STAT1, and FOXK1 mRNAs to regulate autophagy, affecting SLC7A11 lysosomal degradation, GPX4 expression, and ferroptosis. |
| Biological pathway or process: |
fibrosis (promotes); autophagy (inhibits); ferroptosis (promotes); mRNA stability (promotes); other pathway/process (other) |
| Detected method: |
Q
H
S
|
| Validation methods: |
RT-qPCR; RNA-seq; FISH / smFISH; Clinical Sample Validation; RIP (RNA Immunoprecipitation); Actinomycin D / DRB Stability Assay; Transfection; IF (Immunofluorescence); Nuclear-Cytoplasmic Fractionation; Western Blot; In Vivo Animal Model; H&E Staining |
| Clinical significance: |
circFOXP1 expression levels were substantially higher in patients with IPF compared to matched control subjects, suggesting potential as a therapeutic target for MMF-based treatment. |
| Description: |
circFOXP1 is up-regulated in pulmonary fibrosis/IPF and is reduced by MMF treatment. Mechanistically, circFOXP1 interacts with HuR and supports HuR-mediated stabilization of EZH2, STAT1, and FOXK1 mRNAs, thereby suppressing autophagy and favoring ferroptosis and fibrosis. Overexpression of circFOXP1 reverses the anti-fibrotic effects of MMF in cellular and mouse models. |
| Confidence score: |
0.7385 |