| Expression pattern: |
UP |
| Associated gene: |
Foxo3 proteins |
| Associated microRNA: |
- |
| Biological function: |
circFoxo3 promotes I/R- or H/R-induced cardiomyocyte apoptosis/death, mitochondrial damage, apoptotic gene expression, fibrosis and heart graft dysfunction; knockdown of circFoxo3 reduces these injuries and improves heart graft function. |
| Molecular mechanism: |
circFoxo3 binds Foxo3 protein, prevents AKT-mediated Foxo3 phosphorylation, reduces phosphorylated Foxo3 expression, and indirectly affects miR-433 and miR-136 expression. |
| Biological pathway or process: |
apoptosis (promotes); mitochondrial function (inhibits); fibrosis (promotes); other pathway/process (other) |
| Detected method: |
Q
|
| Validation methods: |
Back-Splice Junction PCR / divergent primers PCR; Sanger Sequencing; RT-qPCR; Transfection; Annexin V/PI Flow Cytometry; Flow Cytometry（Non-apoptosis/cycle）; RNA Pull-Down; RIP (RNA Immunoprecipitation); Western Blot; TUNEL; In Vivo Animal Model; H&E Staining |
| Clinical significance: |
circFoxo3 may be a novel therapeutic target for preventing I/R injury in HT. |
| Description: |
In a mouse heart transplantation ischemia-reperfusion injury model and cardiomyocyte H/R model, circFoxo3 is up-regulated and appears to aggravate graft and cardiomyocyte injury. Silencing circFoxo3 reduces apoptosis/death, mitochondrial damage, fibrosis and graft dysfunction. Mechanistically, circFoxo3 interacts with Foxo3 protein and suppresses Foxo3 phosphorylation, with indirect effects on miR-433 and miR-136 expression. |
| Confidence score: |
0.7217 |