| Expression pattern: |
UP |
| Associated gene: |
eIF3j, eIF3a, eIF3b |
| Associated microRNA: |
- |
| Biological function: |
promotes trastuzumab resistance; increases cell viability and colony formation under trastuzumab; decreases ROS |
| Molecular mechanism: |
circRNA-encoded peptide (beta-TrCP-343aa) is produced from circ-beta-TrCP; translation is inhibited by eIF3j; promotes NRF2 stabilization by blocking SCFbeta-TrCP-mediated proteasomal degradation (KEAP1-independent), increasing antioxidant gene transcription and trastuzumab resistance; positive feedback via NRF2 repression of eIF3j |
| Biological pathway or process: |
drug resistance (promotes); oxidative phosphorylation (other); other pathway/process (other) |
| Detected method: |
Q
S
|
| Validation methods: |
circRNA-seq; RT-qPCR; Clinical Sample Validation; RNase R Treatment; Northern Blot; Sanger Sequencing; Actinomycin D / DRB Stability Assay; Nuclear-Cytoplasmic Fractionation; FISH / smFISH; Transfection; CCK8; Colony Formation Assay; Flow Cytometry（Non-apoptosis/cycle）; In Vivo Animal Model; RIP (RNA Immunoprecipitation); RNA Pull-Down; Western Blot; Co-IP; IHC (Immunohistochemistry); Luciferase Reporter Assay; ChIP / ChIP-seq; ROC Analysis; Survival Analysis; Bioinformatics Analysis |
| Clinical significance: |
High circ-beta-TrCP is associated with shorter overall survival; plasma circ-beta-TrCP is higher in resistant patients and shows diagnostic efficiency for trastuzumab response (AUC 0.9037). |
| Description: |
circ-beta-TrCP is upregulated in trastuzumab-resistant HER2-positive breast cancer tissues and plasma and promotes trastuzumab resistance in vitro and in vivo. It functions mainly via encoding the peptide beta-TrCP-343aa, whose translation is inhibited by eIF3j, and which stabilizes NRF2 by competitively blocking SCFbeta-TrCP-mediated NRF2 degradation, enhancing NRF2-driven antioxidant programs and forming a positive feedback loop (NRF2 represses eIF3j) that accelerates resistance. |
| Confidence score: |
0.9031 |