| Expression pattern: |
DN |
| Associated gene: |
ENO1, Klf2, FUS |
| Associated microRNA: |
- |
| Biological function: |
Mediates exercise-induced neuroprotection by inhibiting microglial/macrophage pyroptosis and reducing neuroinflammation after ischemic stroke; reduces infarct volume and improves neurological recovery. |
| Molecular mechanism: |
circFndc3b binds ENO1 and acts as a scaffold to enhance ENO1 binding to Klf2 mRNA 3′UTR, stabilizing Klf2 mRNA and increasing Klf2 protein, thereby suppressing NLRP3 inflammasome-mediated pyroptosis; also enhances ENO1 interaction with FUS mRNA to increase FUS and promote circFndc3b cyclization (positive feedback). |
| Biological pathway or process: |
pyroptosis (inhibits); inflammation (inhibits); NLRP3 inflammasome (inhibits); mRNA stability (promotes); other pathway/process (other) |
| Detected method: |
Q
S
|
| Validation methods: |
circRNA-seq; RT-qPCR; Sanger Sequencing; divergent primers PCR; FISH / smFISH; Nuclear-Cytoplasmic Fractionation; RNA Pull-Down; RIP (RNA Immunoprecipitation); LC-MS; Luciferase Reporter Assay; Actinomycin D / DRB Stability Assay; Transfection; Western Blot; IF (Immunofluorescence); In Vivo Animal Model |
| Clinical significance: |
- |
| Description: |
In MCAO ischemic stroke mice, circFndc3b is reduced in the penumbral/peri-infarct cortex, while exercise restores/increases its expression in microglia/macrophages and improves neurological outcomes. circFndc3b binds the RBP ENO1 to enhance ENO1-mediated stabilization of Klf2 mRNA (and also FUS mRNA), thereby increasing Klf2 to suppress NLRP3 inflammasome-driven pyroptosis; the ENO1/FUS arm promotes circFndc3b cyclization, forming a positive feedback loop. |
| Confidence score: |
0.8065 |