| Expression pattern: |
UP |
| Associated gene: |
PRKDC, PD-L1, EIF4A3, AGO2 |
| Associated microRNA: |
miR-375-3p |
| Biological function: |
Promotes gastric cancer cell proliferation, tumor growth, and tumor immune escape (reducing antitumor T cell effects and promoting an immunosuppressive tumor microenvironment). |
| Molecular mechanism: |
Acts as a miR-375 sponge to upregulate PRKDC (DNA-PK), which promotes PD-L1 phosphorylation and stabilization, driving immune escape. |
| Biological pathway or process: |
proliferation (promotes); immune regulation (promotes); ceRNA regulation (promotes) |
| Detected method: |
Q
H
M
|
| Validation methods: |
Microarray; Bioinformatics Analysis; RT-qPCR; FISH / smFISH; Nuclear-Cytoplasmic Fractionation; divergent primers PCR; Back-Splice Junction PCR; Sanger Sequencing; RNase R Treatment; Actinomycin D / DRB Stability Assay; Luciferase Reporter Assay; RIP (RNA Immunoprecipitation); Transfection; CCK8; Flow Cytometry（Non-apoptosis/cycle）; IF (Immunofluorescence); Western Blot; Co-IP; In Vivo Animal Model; ELISA |
| Clinical significance: |
Higher expression in gastric cancer tissue sections (including different stages); proposed as an immune target and rationale to enhance anti-PD-L1 therapy. |
| Description: |
hsa_circ_0136666 is upregulated in gastric cancer tissues/cells and promotes proliferation and immune escape. It functions mainly as a ceRNA by sponging miR-375-3p to increase PRKDC (DNA-PK), which stabilizes PD-L1 via phosphorylation, contributing to an immunosuppressive tumor microenvironment and reduced CD8+ T-cell antitumor activity. Targeting hsa_circ_0136666 with LNP-siRNA can enhance anti-PD-L1 therapeutic efficacy in mouse tumor models. |
| Confidence score: |
0.8225 |