| Expression pattern: |
UP |
| Associated gene: |
HIF1alpha, DDB1, DDB2, CRL4DDB2 E3 ubiquitin ligase, p27 |
| Associated microRNA: |
- |
| Biological function: |
promotes proliferation; promotes tumorigenesis; increases cell cycle progression; inhibits apoptosis |
| Molecular mechanism: |
HIF1alpha binds to the PFKFB4 promoter to induce circPFKFB4 biogenesis under hypoxia; circPFKFB4 directly binds DDB1 and DDB2 to facilitate CRL4DDB2 E3 ligase assembly, stabilizes DDB2, and promotes p27 ubiquitination and degradation |
| Biological pathway or process: |
ubiquitination (promotes); cell cycle (promotes); proliferation (promotes); apoptosis (inhibits); other pathway/process (promotes) |
| Detected method: |
Q
M
|
| Validation methods: |
Microarray; RT-qPCR; Back-Splice Junction PCR / divergent primers PCR; RNase R Treatment; Actinomycin D / DRB Stability Assay; Sanger Sequencing; Nuclear-Cytoplasmic Fractionation; FISH / smFISH; ISH (In Situ Hybridization); Clinical Sample Validation; RIP (RNA Immunoprecipitation); RNA Pull-Down; Co-IP; Luciferase Reporter Assay; ChIP / ChIP-seq; Transfection; CCK8; EdU Staining; Colony Formation Assay; Annexin V/PI Flow Cytometry; Cell Cycle Assay; TUNEL; Western Blot; In Vivo Animal Model; IHC (Immunohistochemistry); Survival Analysis; ROC Analysis; Bioinformatics Analysis |
| Clinical significance: |
Highly expressed in BC tissues/cell lines; positively correlated with advanced clinical stage; higher expression associated with poor prognosis; potential diagnostic value (ROC AUC 0.677); independent predictor of poor prognosis |
| Description: |
circPFKFB4 (hsa_circ_0124008) is induced by hypoxia in BC and is up-regulated in tumors, where high expression predicts poor prognosis. It promotes BC cell proliferation and tumor growth by binding DDB1/DDB2 to enhance CRL4DDB2 assembly and drive p27 ubiquitination and degradation, facilitating cell-cycle progression under hypoxia. |
| Confidence score: |
0.904 |