| Expression pattern: |
UP |
| Associated gene: |
RBM4, NBR1 mRNA, MHC-I |
| Associated microRNA: |
- |
| Biological function: |
promotes autophagy, induces MHC-I degradation, suppresses CD8+ T cell cytotoxicity, and promotes tumor immune escape and tumor growth in RCC |
| Molecular mechanism: |
circGRAMD4 binds RBM4 and forms a ternary complex with RBM4 and NBR1 mRNA to stabilize NBR1 mRNA, increasing NBR1 expression and promoting autophagy-mediated MHC-I degradation |
| Biological pathway or process: |
autophagy (promotes); immune regulation (other); other pathway/process (other) |
| Detected method: |
Q
S
M
|
| Validation methods: |
Microarray; RNA-seq; Bioinformatics Analysis; RT-qPCR; Back-Splice Junction PCR / divergent primers PCR; Sanger Sequencing; RNase R Treatment; Actinomycin D / DRB Stability Assay; Nuclear-Cytoplasmic Fractionation; FISH / smFISH; RNA Pull-Down; RIP (RNA Immunoprecipitation); Luciferase Reporter Assay; Transfection; Western Blot; IF (Immunofluorescence); IHC (Immunohistochemistry); Flow Cytometry（Non-apoptosis/cycle）; In Vivo Animal Model; Clinical Sample Validation; Cohort Study; Survival Analysis |
| Clinical significance: |
High circGRAMD4 expression is associated with dismal OS and PFS and poor prognosis in RCC patients. |
| Description: |
circGRAMD4 is up-regulated in RCC and promotes immune escape. It binds the RBP RBM4 and facilitates formation of a ternary complex with NBR1 mRNA to stabilize NBR1, thereby enhancing autophagy-dependent degradation of MHC-I, impairing antigen presentation and CD8+ T cell cytotoxicity. High circGRAMD4 associates with poor OS/PFS and its inhibition synergizes with PDCD1 blockade in PDX models. |
| Confidence score: |
0.8981 |