| Expression pattern: |
UP |
| Associated gene: |
MyD88, NF-kappaB, IL6, STAT3 |
| Associated microRNA: |
miR-203a-3p |
| Biological function: |
Induces iCAF phenotype in fibroblasts; promotes PDAC progression by enhancing IL6 secretion; promotes tumorigenesis and metastasis; enhances gemcitabine resistance |
| Molecular mechanism: |
ceRNA mechanism: circCUL2 sponges miR-203a-3p, derepresses MyD88 and activates MyD88-dependent NF-kappaB signaling, increasing IL6 secretion; IL6 activates STAT3 signaling in pancreatic cancer cells |
| Biological pathway or process: |
NF-kappaB (promotes); JAK/STAT (promotes); inflammation (promotes); proliferation (promotes); migration (promotes); invasion (promotes); metastasis (promotes); drug resistance (promotes); ceRNA regulation (promotes) |
| Detected method: |
Q
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; RNA Pull-Down; Luciferase Reporter Assay; Transfection; ELISA; Western Blot; Colony Formation Assay; Transwell Assay; Wound Healing Assay; EdU Staining; In Vivo Animal Model; IHC (Immunohistochemistry); H&E Staining; Clinical Sample Validation; Cohort Study; Survival Analysis; ROC Analysis; Bioinformatics Analysis |
| Clinical significance: |
High circCUL2 expression in PDAC tissues correlates with lymph node metastasis and late clinical stage, predicts poorer OS and DFS, and has diagnostic value by ROC analysis. |
| Description: |
circCUL2 is up-regulated in PDAC stroma/CAFs and drives normal fibroblasts toward an inflammatory CAF (iCAF) phenotype. It acts as a ceRNA sponge for miR-203a-3p to increase MyD88 and activate NF-kappaB signaling, elevating IL6 secretion, which in turn activates STAT3 in PDAC cells to promote proliferation, migration/invasion, tumor growth and metastasis; high circCUL2 associates with poor patient survival. |
| Confidence score: |
0.8909 |