| Expression pattern: |
UP |
| Associated gene: |
PKM2, KPNA2, IL-8, c-Myc, GLUT1, LDHA |
| Associated microRNA: |
- |
| Biological function: |
Promotes glycolysis reprogramming in CAFs and induces oxaliplatin resistance in pancreatic cancer cells; decreases oxaliplatin-induced apoptosis; enhances DNA damage repair. |
| Molecular mechanism: |
circABCC4 binds PKM2 and KPNA2, enhances PKM2-KPNA2 interaction and promotes PKM2 nuclear translocation in CAFs, activating transcription of glycolysis-related genes and increasing IL-8 secretion to promote DNA repair and oxaliplatin resistance. |
| Biological pathway or process: |
glycolysis (promotes); NF-kappaB (promotes); drug resistance (promotes); apoptosis (inhibits); ceRNA regulation (other) |
| Detected method: |
Q
H
S
|
| Validation methods: |
circRNA-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); RNA Pull-Down; RIP (RNA Immunoprecipitation); Co-IP; Transfection; CCK8; Colony Formation Assay; Annexin V/PI Flow Cytometry; Western Blot; Luciferase Reporter Assay; ELISA; In Vivo Animal Model; IF (Immunofluorescence); IHC (Immunohistochemistry); TUNEL; Survival Analysis; Bioinformatics Analysis |
| Clinical significance: |
Higher circABCC4 expression is associated with poor platinum-chemotherapeutic response and shorter progression-free survival (PFS) in late-stage PDAC patients; may serve as a biomarker for oxaliplatin resistance. |
| Description: |
circABCC4 is up-regulated in CAFs and PDAC tissues from oxaliplatin-resistant patients and promotes oxaliplatin resistance. It directly associates with PKM2 and KPNA2 to enhance PKM2 nuclear translocation in CAFs, driving glycolysis reprogramming and IL-8 secretion, which reduces DNA damage in PDAC cells and supports chemoresistance. High circABCC4 predicts poor oxaliplatin response and shorter PFS. |
| Confidence score: |
0.8988 |