| Expression pattern: |
UP |
| Associated gene: |
IGF2BP2, SLC7A11, SLC7A11 mRNA |
| Associated microRNA: |
- |
| Biological function: |
enhances sorafenib resistance by suppressing ferroptosis and promoting SLC7A11 expression/system Xc- function in HCC cells |
| Molecular mechanism: |
forms a circUPF2-IGF2BP2-SLC7A11 ternary complex to stabilize SLC7A11 mRNA |
| Biological pathway or process: |
ferroptosis (inhibits); drug resistance (promotes); mRNA stability (promotes); oxidative phosphorylation (other) |
| Detected method: |
Q
S
|
| Validation methods: |
RNA-seq; RT-qPCR; Back-Splice Junction PCR / divergent primers PCR; RNase R Treatment; Sanger Sequencing; Actinomycin D / DRB Stability Assay; RNA Pull-Down; RIP (RNA Immunoprecipitation); Luciferase Reporter Assay; Transfection; CCK8; Colony Formation Assay; FISH / smFISH; IF (Immunofluorescence); Western Blot; In Vivo Animal Model; IHC (Immunohistochemistry); TUNEL; Bioinformatics Analysis |
| Clinical significance: |
circulating exosomal hsa_circ_0017702 is elevated in HCC patients with imaging-confirmed progressive disease after sorafenib treatment; circUPF2 may serve as a potential biomarker/therapeutic target for sorafenib-resistant HCC |
| Description: |
This study identifies exosome-enriched circUPF2 (hsa_circ_0017702) as an effector of acquired sorafenib resistance in HCC. circUPF2 serves as a cytoplasmic scaffold recruiting IGF2BP2 and SLC7A11 mRNA to form a ternary complex that stabilizes SLC7A11 mRNA, enhances system Xc- activity, suppresses ferroptosis, and reduces sorafenib efficacy in vitro and in xenografts. |
| Confidence score: |
0.8546 |