| Expression pattern: |
UP |
| Associated gene: |
PKR, IKKbeta, RELA, IkappaBalpha |
| Associated microRNA: |
- |
| Biological function: |
Promotes metastasis (migration and invasion) and supports chemotherapy-induced senescence-associated proinflammatory SASP in NPC; circWDR37 deficiency enhances chemotherapy-induced senescence but inhibits metastasis. |
| Molecular mechanism: |
circWDR37 binds PKR (dsRBMs domain) and induces PKR homodimerization and phosphorylation, which activates NF-kappaB signaling to induce CCND1 and SASP gene transcription. |
| Biological pathway or process: |
NF-kappaB (promotes); metastasis (promotes); migration (promotes); invasion (promotes); proliferation (promotes); ceRNA regulation (other); other pathway/process (other) |
| Detected method: |
Q
S
M
|
| Validation methods: |
Back-Splice Junction PCR / divergent primers PCR; Sanger Sequencing; RNase R Treatment; Actinomycin D / DRB Stability Assay; RT-qPCR; Nuclear-Cytoplasmic Fractionation; FISH / smFISH; RNA Pull-Down; RIP (RNA Immunoprecipitation); Co-IP; Luciferase Reporter Assay; Transfection; Transwell Assay; Colony Formation Assay; In Vivo Animal Model; H&E Staining; IHC (Immunohistochemistry); Western Blot; Clinical Sample Validation; Cohort Study; Survival Analysis; Bioinformatics Analysis; Microarray |
| Clinical significance: |
High circWDR37 expression indicates unfavorable prognosis and is associated with distant metastasis; low circWDR37 levels associate with better response and survival benefit from cisplatin or gemcitabine induction chemotherapy. |
| Description: |
In nasopharyngeal carcinoma, circWDR37 is upregulated in highly metastatic cells and promotes chemotherapy-induced senescence-associated metastasis. It binds PKR in the cytoplasm, induces PKR homodimerization/phosphorylation, activates NF-kappaB, and increases CCND1 and proinflammatory SASP gene transcription, leading to enhanced migration/invasion. Clinically, high circWDR37 associates with poor survival and reduced induction-chemotherapy benefit. |
| Confidence score: |
0.9016 |