| Expression pattern: |
UP |
| Associated gene: |
PKP3, METTL3, YTHDC1, PD-L1, OTUB1, FXR1 |
| Associated microRNA: |
miR-328-3p, miR-3173-5p |
| Biological function: |
promotes tumor immune evasion by inhibiting CD8+ T cell responses and compromising antitumor immunity |
| Molecular mechanism: |
m6A modification (METTL3/YTHDC1-dependent) promotes circIGF2BP3 circularization; circIGF2BP3 sponges miR-328-3p and miR-3173-5p to upregulate PKP3; PKP3 stabilizes OTUB1 mRNA via FXR1, increasing PD-L1 deubiquitination and immune escape |
| Biological pathway or process: |
immune regulation (inhibits); ceRNA regulation (promotes); other pathway/process (promotes) |
| Detected method: |
Q
M
|
| Validation methods: |
Microarray; Bioinformatics Analysis; RT-qPCR; RNase R Treatment; Sanger Sequencing; divergent primers PCR; Actinomycin D / DRB Stability Assay; FISH / smFISH; Nuclear-Cytoplasmic Fractionation; Luciferase Reporter Assay; RIP (RNA Immunoprecipitation); RNA Pull-Down; Transfection; Flow Cytometry（Non-apoptosis/cycle）; Annexin V/PI Flow Cytometry; IF (Immunofluorescence); ELISA; Western Blot; In Vivo Animal Model; IHC (Immunohistochemistry); Survival Analysis |
| Clinical significance: |
high circIGF2BP3 expression correlated with shorter overall survival and was an independent prognostic marker in NSCLC |
| Description: |
circIGF2BP3 is upregulated in NSCLC and suppresses CD8+ T cell-mediated antitumor immunity. It acts as an m6A-regulated cytoplasmic ceRNA that sponges miR-328-3p/miR-3173-5p to increase PKP3, ultimately promoting OTUB1-dependent PD-L1 deubiquitination and tumor immune evasion, and high expression predicts poor overall survival. |
| Confidence score: |
0.8816 |