| Expression pattern: |
UP |
| Associated gene: |
AR-V7, AR, HSP70, STUB1, eIF4A3, DDX39A |
| Associated microRNA: |
- |
| Biological function: |
promotes enzalutamide resistance in CRPC cells; increases AR-V7 protein stability by inhibiting ubiquitin-proteasome degradation; promotes tumor growth/tolerance to ENZ in xenograft model |
| Molecular mechanism: |
circRNA-encoded peptide mechanism: circSRCAP encodes circSRCAP-75aa which binds HSP70, disrupts HSP70-STUB1 interaction, inhibits STUB1-mediated ubiquitination/degradation (ubiquitin-proteasome pathway) leading to stabilized AR/AR-V7 and ENZ resistance; circSRCAP biogenesis/export regulated by eIF4A3 and DDX39A |
| Biological pathway or process: |
drug resistance (promotes); ubiquitination (inhibits); other pathway/process (other) |
| Detected method: |
Q
S
|
| Validation methods: |
circRNA-seq; RT-qPCR; RNase R Treatment; Sanger Sequencing; Back-Splice Junction PCR / divergent primers PCR; Actinomycin D / DRB Stability Assay; Nuclear-Cytoplasmic Fractionation; FISH / smFISH; Transfection; Western Blot; Co-IP; RIP (RNA Immunoprecipitation); RNA Pull-Down; Luciferase Reporter Assay; CCK8; In Vivo Animal Model; IHC (Immunohistochemistry); Bioinformatics Analysis |
| Clinical significance: |
potential therapeutic target for ENZ-resistant CRPC |
| Description: |
circSRCAP is up-regulated in ENZ-resistant CRPC cells and promotes enzalutamide resistance. It functions mainly by encoding a 75-aa peptide (circSRCAP-75aa) that binds HSP70, disrupts HSP70-STUB1-dependent ubiquitination, stabilizes AR/AR-V7, and thereby increases AR-V7 protein levels. |
| Confidence score: |
0.8595 |