| Expression pattern: |
DN |
| Associated gene: |
HuR, beta-TrCP, p21 |
| Associated microRNA: |
miR-133a |
| Biological function: |
prevents cardiomyocyte senescence, promotes cardiomyocyte proliferation, and improves cardiac function |
| Molecular mechanism: |
circHIPK3 acts as a scaffold to recruit HuR and E3 ubiquitin ligase beta-TrCP, promoting HuR ubiquitination/degradation, thereby reducing p21 mRNA stability and p21 activity |
| Biological pathway or process: |
ubiquitination (promotes); mRNA stability (inhibits); proliferation (promotes); apoptosis (not specified); cell cycle (other); ceRNA regulation (other) |
| Detected method: |
Q
S
|
| Validation methods: |
RNA-seq; RT-qPCR; RNase R Treatment; RNA Pull-Down; RIP (RNA Immunoprecipitation); Co-IP; Western Blot; Nuclear-Cytoplasmic Fractionation; IF (Immunofluorescence); Actinomycin D / DRB Stability Assay; Transfection; EdU Staining; In Vivo Animal Model |
| Clinical significance: |
UMSC-Exos exerted an anti-senescence and cardio-protective effect by delivering circHIPK3, suggesting therapeutic potential for aging-associated cardiac dysfunction |
| Description: |
In aging hearts, circHIPK3 is down-regulated. Functionally, circHIPK3 suppresses cardiomyocyte senescence and supports cardiac function by scaffolding HuR with the E3 ligase beta-TrCP in the cytoplasm, promoting HuR ubiquitination/degradation and reducing p21 mRNA stabilization. UMSC-derived exosomes can deliver circHIPK3 to confer anti-senescence and cardioprotective effects. |
| Confidence score: |
0.7753 |