| Expression pattern: |
UP |
| Associated gene: |
YWHAG, RAF1, ERK, MEK1/2, Trametinib |
| Associated microRNA: |
miR-6884-5p |
| Biological function: |
Promotes ICC cell proliferation, colony formation, tumor growth, and Trametinib resistance; inhibits apoptosis; does not affect invasion and migration abilities. |
| Molecular mechanism: |
circNOX4 acts as a ceRNA by sponging hsa-miR-6884-5p to upregulate YWHAG; YWHAG binds RAF1, enhances RAF1 phosphorylation, activates RAF/MEK/ERK signaling, promotes p-ERK nuclear translocation, and reduces Trametinib anti-tumor efficacy. |
| Biological pathway or process: |
ERK (promotes); MAPK (promotes); proliferation (promotes); apoptosis (inhibits); cell cycle (promotes); ceRNA regulation (promotes); drug resistance (promotes); other pathway/process (promotes) |
| Detected method: |
Q
|
| Validation methods: |
Back-Splice Junction PCR / divergent primers PCR; RNase R Treatment; Actinomycin D / DRB Stability Assay; RT-qPCR; FISH / smFISH; Nuclear-Cytoplasmic Fractionation; Clinical Sample Validation; RIP (RNA Immunoprecipitation); RNA Pull-Down; Co-IP; Luciferase Reporter Assay; Transfection; CCK8; EdU Staining; Colony Formation Assay; Annexin V/PI Flow Cytometry; In Vivo Animal Model; IHC (Immunohistochemistry); IF (Immunofluorescence); Western Blot; Survival Analysis; ROC Analysis; Bioinformatics Analysis; RNA-seq; Cohort Study |
| Clinical significance: |
High circNOX4 expression is associated with larger tumors, advanced stage-T, higher TNM stage, poorer overall survival and recurrence-free survival, and diagnostic value with ROC AUC 0.767; it may serve as a diagnostic marker, prognostic indicator, therapeutic target, and predictor of Trametinib response. |
| Description: |
circNOX4 is an upregulated circRNA in ICC derived from the NOX4 gene and is associated with aggressive clinicopathological features and poor survival. It promotes ICC proliferation and tumor growth while inhibiting apoptosis by sponging hsa-miR-6884-5p to increase YWHAG, which interacts with RAF1 and activates RAF/MEK/ERK signaling. circNOX4 also reduces Trametinib sensitivity, supporting its potential as a diagnostic/prognostic biomarker and therapeutic target. |
| Confidence score: |
0.8999 |