| Expression pattern: |
UP |
| Associated gene: |
OTUB1, SLC7A11 |
| Associated microRNA: |
- |
| Biological function: |
Confers trastuzumab resistance, promotes breast cancer cell viability, inhibits ferroptosis, and its knockdown restores trastuzumab sensitivity. |
| Molecular mechanism: |
circ-BGN directly binds OTUB1 and SLC7A11, acts as a bridge to enhance OTUB1-mediated SLC7A11 deubiquitination, stabilizes SLC7A11 protein, increases GSH content and GPX4 activity, and represses ferroptosis. |
| Biological pathway or process: |
ferroptosis (inhibits); drug resistance (promotes); proliferation (promotes); ubiquitination (inhibits); other pathway/process (promotes) |
| Detected method: |
Q
H
S
|
| Validation methods: |
RNase R Treatment; circRNA-seq; RT-qPCR; ISH (In Situ Hybridization); Clinical Sample Validation; RIP (RNA Immunoprecipitation); RNA Pull-Down; Co-IP; Transfection; CCK8; ELISA; Western Blot; IHC (Immunohistochemistry); In Vivo Animal Model; Survival Analysis; Bioinformatics Analysis |
| Clinical significance: |
High circ-BGN expression was associated with trastuzumab-resistant tissues and poor overall survival; targeting circ-BGN and ferroptosis may provide a therapeutic strategy for trastuzumab-resistant HER2-positive breast cancer patients. |
| Description: |
circ-BGN is up-regulated in trastuzumab-resistant HER2-positive breast cancer cells and tissues and is associated with poor survival. It promotes trastuzumab resistance by directly binding OTUB1 and SLC7A11, enhancing OTUB1-mediated SLC7A11 deubiquitination and suppressing ferroptosis through the SLC7A11/GSH/GPX4 axis. circ-BGN knockdown decreases tumor cell viability, induces ferroptosis, and restores trastuzumab sensitivity, especially when combined with the ferroptosis inducer erastin. |
| Confidence score: |
0.8703 |