| Expression pattern: |
UP |
| Associated gene: |
PCBP1, U2AF65, p53 pre-mRNA, p53beta, cyclin D1, p21, PUMA, NOXA |
| Associated microRNA: |
- |
| Biological function: |
circEsyt2 promotes VSMC proliferation, migration, phenotype switching/dedifferentiation, neointima formation and neointimal hyperplasia, and inhibits apoptosis and differentiation during vascular remodeling. |
| Molecular mechanism: |
circEsyt2 directly binds PCBP1 and promotes its cytoplasmic retention, thereby inhibiting PCBP1-dependent, U2AF65-mediated alternative splicing of p53 pre-mRNA to p53beta and altering p53 target genes involved in VSMC proliferation and apoptosis. |
| Biological pathway or process: |
proliferation (promotes); migration (promotes); apoptosis (inhibits); cell cycle (promotes); p53 signaling (inhibits); mRNA stability (other); other pathway/process (other) |
| Detected method: |
Q
H
S
|
| Validation methods: |
Back-Splice Junction PCR / divergent primers PCR; RNase R Treatment; Sanger Sequencing; circRNA-seq; Actinomycin D / DRB Stability Assay; RT-qPCR; RNA-seq; FISH / smFISH; IF (Immunofluorescence); Nuclear-Cytoplasmic Fractionation; Clinical Sample Validation; RIP (RNA Immunoprecipitation); RNA Pull-Down; Transfection; CCK8; EdU Staining; Annexin V/PI Flow Cytometry; Transwell Assay; Wound Healing Assay; TUNEL; In Vivo Animal Model; H&E Staining; Oil Red O Staining; Western Blot; Bioinformatics Analysis |
| Clinical significance: |
circEsyt2 expression was much higher in arteries from patients with severe CAD than in patients with mild CAD, suggesting a proatherosclerotic role and potential therapeutic relevance in vascular remodeling-related diseases. |
| Description: |
circEsyt2 is upregulated in atherosclerotic and injured vessels and in severe CAD arteries, and it promotes VSMC remodeling by enhancing proliferation and migration while suppressing apoptosis and differentiation. Mechanistically, circEsyt2 binds PCBP1 in the cytoplasm, limits PCBP1 nuclear translocation, suppresses PCBP1/U2AF65-dependent p53beta splicing, and thereby alters p53 target genes that control VSMC proliferation and apoptosis. |
| Confidence score: |
0.8469 |