| Expression pattern: |
UP |
| Associated gene: |
FXR1, TRIM56, ELF4, IRF4 |
| Associated microRNA: |
- |
| Biological function: |
induces M2 polarization of macrophages; promotes anti-inflammatory phenotype in macrophages; induces exhaustion/dysfunction of cytotoxic CD8+ T cells; restrains sensitivity to anti-PD1 treatment |
| Molecular mechanism: |
circZNF451 forms a complex with TRIM56 and FXR1, acting as a scaffold to enhance TRIM56-mediated ubiquitination and degradation of FXR1, thereby activating the ELF4-IRF4 pathway in macrophages |
| Biological pathway or process: |
immune regulation (promotes); macrophage polarization (promotes) |
| Detected method: |
Q
H
S
|
| Validation methods: |
circRNA-seq; RT-qPCR; RNase R Treatment; Sanger Sequencing; FISH / smFISH; Nuclear-Cytoplasmic Fractionation; Clinical Sample Validation; Survival Analysis; Bioinformatics Analysis; RNA Pull-Down; RIP (RNA Immunoprecipitation); Luciferase Reporter Assay; Transfection; Co-IP; Western Blot; Flow Cytometry（Non-apoptosis/cycle）; ELISA; ChIP / ChIP-seq; In Vivo Animal Model; IHC (Immunohistochemistry); IF (Immunofluorescence) |
| Clinical significance: |
elevated/exosomal circZNF451 is associated with poor prognosis of LUAD patients and predicts sensitivity to PD1 blockade (higher in PD than PR) |
| Description: |
In LUAD, exosomal circZNF451 is up-regulated in patients resistant to PD1 blockade and associates with poor prognosis. Mechanistically, it scaffolds TRIM56 and FXR1 in macrophages to promote FXR1 ubiquitination/degradation, activating the ELF4-IRF4 program to drive M2-like polarization and suppress CD8+ T cell cytotoxicity, reducing anti-PD1 efficacy. |
| Confidence score: |
0.8926 |