| Expression pattern: |
UP |
| Associated gene: |
NF-kappaB p65 |
| Associated microRNA: |
- |
| Biological function: |
sensitizes tumor-specific CTLs to activation-induced cell death (AICD), fostering tumor immune escape and resistance to immunotherapy |
| Molecular mechanism: |
histone lactylation activates transcription of circATXN7; circATXN7 binds NF-kappaB p65 and masks its nuclear localization signal, sequestering p65 in the cytoplasm and inactivating NF-kappaB |
| Biological pathway or process: |
NF-kappaB (inhibits); apoptosis (promotes); immune regulation (other pathway/process) |
| Detected method: |
Q
H
S
|
| Validation methods: |
circRNA-seq; Bioinformatics Analysis; RIP (RNA Immunoprecipitation); Transfection; circRNA Pull-Down; RNA Pull-Down; Luciferase Reporter Assay; RT-qPCR; RNase R Treatment; Actinomycin D / DRB Stability Assay; Nuclear-Cytoplasmic Fractionation; FISH / smFISH; ISH (In Situ Hybridization); IF (Immunofluorescence); Western Blot; In Vivo Animal Model; IHC (Immunohistochemistry); RNA-seq; Survival Analysis; Cohort Study |
| Clinical significance: |
circATXN7 upregulation in tumor-specific CTLs correlates with adverse clinical outcomes and immunotherapeutic resistance; high density of circATXN7+ cells correlates with shortened DFS/OS (and PFS in an independent cohort) and lower response to ICIs |
| Description: |
circATXN7 is upregulated in tumor-specific CTLs in KRAS-mutant tumors and promotes tumor immune escape by sensitizing CTLs to activation-induced cell death. It is induced by lactate-driven histone lactylation and directly binds NF-kappaB p65 to block its nuclear translocation, thereby inhibiting NF-kappaB activity. High circATXN7 in CTLs is associated with worse survival and reduced response to immune checkpoint inhibitors, while circATXN7 loss in CD8+ T cells improves antitumor immunity and anti-PD1/ACT efficacy. |
| Confidence score: |
0.8921 |