| Expression pattern: |
UN |
| Associated gene: |
HSPB1 protein, paritaprevir |
| Associated microRNA: |
- |
| Biological function: |
crVDAC3 confers T-DXd resistance in HER2-low breast cancer, reduces sensitivity to T-DXd, inhibits ferroptosis, and supports breast cancer cell survival under T-DXd treatment. |
| Molecular mechanism: |
crVDAC3 binds HSPB1 protein and inhibits HSPB1 ubiquitination degradation, leading to HSPB1 accumulation and suppression of ferroptosis; paritaprevir binds crVDAC3 and disrupts the crVDAC3-HSPB1 interaction to promote HSPB1 ubiquitination degradation and overcome T-DXd resistance. |
| Biological pathway or process: |
ferroptosis (inhibits); ubiquitination (inhibits); drug resistance (promotes); proliferation (promotes) |
| Detected method: |
Q
|
| Validation methods: |
Back-Splice Junction PCR / divergent primers PCR; RNase R Treatment; Sanger Sequencing; Actinomycin D / DRB Stability Assay; RT-qPCR; Nuclear-Cytoplasmic Fractionation; RIP (RNA Immunoprecipitation); RNA Pull-Down; Co-IP; Transfection; CCK8; Colony Formation Assay; Annexin V/PI Flow Cytometry; Flow Cytometry（Non-apoptosis/cycle）; In Vivo Animal Model; H&E Staining; IHC (Immunohistochemistry); Western Blot; Bioinformatics Analysis |
| Clinical significance: |
Targeting the crVDAC3-HSPB1 interaction may be a therapeutic strategy to overcome T-DXd resistance in HER2-low breast cancer. |
| Description: |
crVDAC3 is a VDAC3-derived human circular RNA identified as a key mediator of T-DXd resistance in HER2-low breast cancer. It binds HSPB1 protein and blocks HSPB1 ubiquitination degradation, suppressing ferroptosis and thereby reducing T-DXd sensitivity. Paritaprevir disrupts the crVDAC3-HSPB1 interaction and enhances T-DXd efficacy in preclinical HER2-low breast cancer models. |
| Confidence score: |
0.8479 |