| Expression pattern: |
UP |
| Associated gene: |
XRCC4, SUMO1, SAE1, EIF4A3 |
| Associated microRNA: |
- |
| Biological function: |
promotes oxaliplatin (platinum) resistance/chemoresistance in PDAC; enhances NHEJ-dependent DNA repair; attenuates oxaliplatin-induced apoptosis |
| Molecular mechanism: |
EV-delivered circBIRC6 binds XRCC4 and facilitates SUMO1-mediated SUMOylation of XRCC4 (K115), enhancing XRCC4 chromatin/nuclear localization and NHEJ repair, leading to oxaliplatin resistance; EIF4A3 promotes circBIRC6 biogenesis |
| Biological pathway or process: |
NHEJ (promotes); DNA repair (promotes); apoptosis (inhibits); chemoresistance (promotes); other pathway/process (promotes) |
| Detected method: |
Q
H
S
|
| Validation methods: |
RNA-seq; RT-qPCR; RNase R Treatment; Actinomycin D / DRB Stability Assay; Sanger Sequencing; Back-Splice Junction PCR / divergent primers PCR; FISH / smFISH; Nuclear-Cytoplasmic Fractionation; Clinical Sample Validation; ISH (In Situ Hybridization); RIP (RNA Immunoprecipitation); RNA Pull-Down; Co-IP; Transfection; CCK8; Colony Formation Assay; Annexin V/PI Flow Cytometry; Western Blot; IF (Immunofluorescence); In Vivo Animal Model; IHC (Immunohistochemistry); TUNEL; Survival Analysis; Bioinformatics Analysis |
| Clinical significance: |
High circBIRC6 is associated with oxaliplatin resistance and shorter PFS; plasma EV-packaged circBIRC6 may serve as a biomarker for oxaliplatin-based chemoresistance |
| Description: |
In PDAC, CAF-derived extracellular vesicles deliver circBIRC6 to tumor cells, increasing oxaliplatin/platinum chemoresistance. circBIRC6 binds XRCC4 and promotes SUMO1-dependent SUMOylation at XRCC4 K115, enhancing XRCC4 chromatin/nuclear localization and NHEJ DNA repair, thereby reducing DNA damage and apoptosis. High (plasma EV or tissue) circBIRC6 correlates with oxaliplatin resistance and shorter PFS, supporting its value as a predictive biomarker and therapeutic target (e.g., ASO-circBIRC6 in PDX). |
| Confidence score: |
0.8941 |