| Expression pattern: |
UP |
| Associated gene: |
GSDME, GSDME-C domain, GSDME-N domain, ZDHHC3, ZDHHC17, XBP1, AGO2, PDIA3 |
| Associated microRNA: |
miR-449a |
| Biological function: |
circPDIA3 promotes oxaliplatin chemoresistance in colorectal cancer by inhibiting GSDME-dependent pyroptosis; high circPDIA3 expression is associated with recurrence/metastasis and poor disease-free survival after OXA-based chemotherapy. |
| Molecular mechanism: |
circPDIA3 directly binds the GSDME-C domain and enhances its autoinhibitory interaction with GSDME-N by inhibiting ZDHHC3/ZDHHC17-dependent GSDME-C palmitoylation; circPDIA3 also sponges miR-449a to upregulate XBP1, while XBP1 promotes circPDIA3 expression, forming a positive feedback loop. |
| Biological pathway or process: |
pyroptosis (inhibits); chemoresistance (promotes); drug resistance (promotes); ceRNA regulation (promotes); other pathway/process (inhibits); apoptosis (inhibits); proliferation (promotes) |
| Detected method: |
Q
B
S
M
|
| Validation methods: |
Back-Splice Junction PCR / divergent primers PCR; RNase R Treatment; Sanger Sequencing; Actinomycin D / DRB Stability Assay; RT-qPCR; RNA-seq; Microarray; Northern Blot; FISH / smFISH; IF (Immunofluorescence); Nuclear-Cytoplasmic Fractionation; Clinical Sample Validation; RIP (RNA Immunoprecipitation); RNA Pull-Down; Co-IP; ChIP / ChIP-seq; Luciferase Reporter Assay; Transfection; CCK8; EdU Staining; Colony Formation Assay; Annexin V/PI Flow Cytometry; In Vivo Animal Model; H&E Staining; IHC (Immunohistochemistry); ELISA; Western Blot; Cohort Study; Survival Analysis; Bioinformatics Analysis |
| Clinical significance: |
circPDIA3 is closely associated with unfavorable clinical prognosis and can act as an independent predictor of OXA response in CRC patients; high circPDIA3 expression is associated with recurrence/metastasis and lower DFS. |
| Description: |
circPDIA3 is an upregulated PDIA3-derived circular RNA in CRC, especially in oxaliplatin-resistant tumors, and high expression predicts poorer disease-free survival after OXA-based therapy. Functionally, circPDIA3 promotes chemoresistance by suppressing GSDME-dependent pyroptosis through direct binding to the GSDME-C domain and inhibition of ZDHHC3/ZDHHC17-mediated palmitoylation. It also forms a circPDIA3/miR-449a/XBP1 positive feedback loop that further increases circPDIA3 expression and reinforces OXA resistance. |
| Confidence score: |
0.9043 |