| Expression pattern: |
UP |
| Associated gene: |
FXR1, ECT2 mRNA, JNK, Bim, Caspase 3, bax, Ki-67 |
| Associated microRNA: |
- |
| Biological function: |
Promotes acquired gefitinib resistance in NSCLC cells, increases cell viability under gefitinib treatment, inhibits apoptosis, and suppresses gefitinib efficacy in vivo. |
| Molecular mechanism: |
circSETD3 binds the RNA-binding protein FXR1 in the cytoplasm, facilitates FXR1 recruitment to ECT2 mRNA, promotes ECT2 mRNA decay, and inhibits apoptosis through suppression of the JNK/Bim pathway. |
| Biological pathway or process: |
drug resistance (promotes); apoptosis (inhibits); proliferation (promotes); mRNA stability (inhibits); other pathway/process (inhibits) |
| Detected method: |
Q
|
| Validation methods: |
RT-qPCR; Clinical Sample Validation; ROC Analysis; Transfection; CCK8; Annexin V/PI Flow Cytometry; Western Blot; RNA Pull-Down; RIP (RNA Immunoprecipitation); FISH / smFISH; IF (Immunofluorescence); Actinomycin D / DRB Stability Assay; In Vivo Animal Model; H&E Staining; IHC (Immunohistochemistry) |
| Clinical significance: |
circSETD3 might serve as a predictive biomarker for gefitinib resistance and a therapeutic target for NSCLC patients with acquired gefitinib resistance. |
| Description: |
This study shows that circSETD3 is up-regulated in gefitinib-resistant NSCLC cells and patient plasma samples and can serve as a potential predictive biomarker for gefitinib resistance. Functionally, circSETD3 promotes gefitinib resistance by increasing cell viability and suppressing apoptosis in vitro and in cell line-derived xenograft models. Mechanistically, circSETD3 binds FXR1 in the cytoplasm, enhances FXR1-mediated ECT2 mRNA decay, and suppresses the pro-apoptotic JNK/Bim pathway. |
| Confidence score: |
0.823 |