| Expression pattern: |
UP |
| Associated gene: |
PD-L1, STAT3, p-STAT3, IL-6, ANXA1, USP7 |
| Associated microRNA: |
- |
| Biological function: |
promotes proliferation; promotes migration and invasion; promotes immune evasion; promotes resistance/poor response to anti-PD-L1 immunotherapy |
| Molecular mechanism: |
Enhances IL-6-driven JAK-STAT3 activation to promote p-STAT3 binding on PD-L1 promoter and increase PD-L1 transcription; physically binds ANXA1 to block USP7-ANXA1 interaction, shifting USP7 toward PD-L1 deubiquitination to increase PD-L1 stability |
| Biological pathway or process: |
JAK/STAT (promotes); ubiquitination (other); proliferation (promotes); migration (promotes); invasion (promotes); immune regulation (other) |
| Detected method: |
Q
H
M
|
| Validation methods: |
Microarray; RT-qPCR; Clinical Sample Validation; RNase R Treatment; Actinomycin D / DRB Stability Assay; Back-Splice Junction PCR / divergent primers PCR; FISH / smFISH; Nuclear-Cytoplasmic Fractionation; RNA-seq; Bioinformatics Analysis; Western Blot; ChIP / ChIP-seq; RIP (RNA Immunoprecipitation); Co-IP; RNA Pull-Down; Transfection; CCK8; EdU Staining; Colony Formation Assay; Transwell Assay; Wound Healing Assay; TUNEL; ELISA; IHC (Immunohistochemistry); In Vivo Animal Model; ROC Analysis; Survival Analysis; ddPCR |
| Clinical significance: |
circNF1 is elevated in ESCC tissues and serum, has diagnostic value (ROC AUC in tissue and serum), correlates with anti-PD-L1 immunotherapy efficacy, and high circNF1 tends to indicate worse overall survival |
| Description: |
circNF1 is upregulated in ESCC tissues and serum and promotes ESCC proliferation, migration/invasion, and immune escape. It increases PD-L1 by activating the IL-6/JAK-STAT3 pathway to enhance PD-L1 transcription and by binding ANXA1 to favor USP7-mediated PD-L1 deubiquitination, stabilizing PD-L1 and reducing CD8+ T-cell antitumor activity. Clinically, higher circNF1 is associated with poorer response to anti-PD-L1 therapy and worse overall survival. |
| Confidence score: |
0.8991 |