| Expression pattern: |
UP |
| Associated gene: |
CCL22 |
| Associated microRNA: |
miR-1184 |
| Biological function: |
promotes LUAD cell proliferation and migration/invasion; inhibits apoptosis; promotes immune resistance/CTL exhaustion; promotes tumor growth in vivo; may drive resistance to anti-PD-1 immunotherapy |
| Molecular mechanism: |
ceRNA mechanism: circ_0004140 sponges miR-1184 to increase CCL22 expression, promoting malignant phenotypes and immune suppression/CTL exhaustion; CCL22/CCR4 axis involved; combination of C-021 (CCL22 inhibitor) and anti-PD-1 reduces tumor growth and improves survival in xenografts |
| Biological pathway or process: |
proliferation (promotes); migration (promotes); invasion (promotes); apoptosis (inhibits); immune regulation (other); ceRNA regulation (promotes); drug resistance (promotes) |
| Detected method: |
Q
|
| Validation methods: |
RT-qPCR; Sanger Sequencing; RNase R Treatment; Actinomycin D / DRB Stability Assay; FISH / smFISH; RNA Pull-Down; Luciferase Reporter Assay; Transfection; CCK8; Transwell Assay; Wound Healing Assay; Annexin V/PI Flow Cytometry; Western Blot; IHC (Immunohistochemistry); In Vivo Animal Model; Survival Analysis; Bioinformatics Analysis; Clinical Sample Validation |
| Clinical significance: |
High circ_0004140 expression is correlated with poor prognosis and shorter overall survival in LUAD patients |
| Description: |
circ_0004140 (derived from YAP1) is up-regulated in LUAD and correlates with poor prognosis. It promotes proliferation, migration/invasion and suppresses apoptosis, and contributes to immune resistance/CTL exhaustion by sponging miR-1184 to upregulate CCL22. Targeting the CCL22/CCR4 axis (C-021) combined with anti-PD-1 reduced xenograft tumor growth and improved survival, suggesting circ_0004140 as a therapeutic target linked to anti-PD-1 resistance. |
| Confidence score: |
0.8711 |