| Expression pattern: |
UP |
| Associated gene: |
WTAP, EP300, EIF4A3, IGF2BP3, IGF2BP2, IGF2BP1, hnRNPA2B1, PD1 |
| Associated microRNA: |
miR-127-5p |
| Biological function: |
promotes HCC growth and metastasis; promotes CD8+ T-cell dysfunction/exhaustion; promotes resistance to anti-PD1 immunotherapy |
| Molecular mechanism: |
ceRNA sponge of miR-127-5p to upregulate WTAP forming circCCAR1/miR-127-5p/WTAP feedback loop; WTAP-mediated m6A modification recruits IGF2BP3 to enhance circCCAR1 stability; hnRNPA2B1-dependent exosomal packaging; direct binding to PD1 protein to inhibit ubiquitination-mediated proteasomal degradation and stabilize PD1 in CD8+ T cells |
| Biological pathway or process: |
proliferation (promotes); migration (promotes); invasion (promotes); metastasis (promotes); apoptosis (promotes); immune regulation (promotes); ceRNA regulation (promotes); m6A modification (promotes); ubiquitination (inhibits); drug resistance (promotes) |
| Detected method: |
Q
H
M
|
| Validation methods: |
Microarray; RT-qPCR; Back-Splice Junction PCR / divergent primers PCR; Sanger Sequencing; Actinomycin D / DRB Stability Assay; RNase R Treatment; Nuclear-Cytoplasmic Fractionation; FISH / smFISH; Clinical Sample Validation; Survival Analysis; Bioinformatics Analysis; Transfection; CCK8; Colony Formation Assay; Wound Healing Assay; Transwell Assay; In Vivo Animal Model; IHC (Immunohistochemistry); H&E Staining; ELISA; Western Blot; Flow Cytometry（Non-apoptosis/cycle）; TUNEL; RIP (RNA Immunoprecipitation); RNA Pull-Down; Luciferase Reporter Assay; MeRIP / MeRIP-seq; Co-IP |
| Clinical significance: |
High circCCAR1 (in tumor tissue and serum exosomes) is associated with poor prognosis and can be regarded as a prognostic indicator; circCCAR1 levels correlate with vascular invasion, tumor grade, TNM stage, and tumor size |
| Description: |
circCCAR1 is up-regulated in HCC tumor tissue and enriched in circulating exosomes. It promotes HCC proliferation and metastasis via a circCCAR1/miR-127-5p/WTAP ceRNA feedback loop and is stabilized by WTAP-mediated m6A with IGF2BP3. Exosomal circCCAR1 enters CD8+ T cells and directly binds PD1 to reduce ubiquitination and proteasomal degradation, driving T-cell dysfunction and anti-PD1 resistance, and higher levels indicate poor prognosis. |
| Confidence score: |
0.8988 |