| Expression pattern: |
DN |
| Associated gene: |
HSP60, SMURF1, RKIP, c-Myc, PD-L1 |
| Associated microRNA: |
- |
| Biological function: |
circCCNY suppresses HCC progression, inhibits proliferation, migration and invasion, enhances lenvatinib sensitivity, increases CD8+ T-cell infiltration, and suppresses immune evasion. |
| Molecular mechanism: |
circCCNY acts as a scaffold for the HSP60/SMURF1 protein complex, promotes SMURF1-mediated K48-linked ubiquitination and degradation of HSP60, releases RKIP, inactivates the MAPK signaling pathway, and downregulates the HSP60/MAPK/c-Myc/PD-L1 axis. |
| Biological pathway or process: |
MAPK (inhibits); proliferation (inhibits); migration (inhibits); invasion (inhibits); ubiquitination (promotes); immune regulation (promotes); drug resistance (inhibits) |
| Detected method: |
Q
H
S
|
| Validation methods: |
Back-Splice Junction PCR / divergent primers PCR; RNase R Treatment; Sanger Sequencing; Actinomycin D / DRB Stability Assay; RT-qPCR; circRNA-seq; FISH / smFISH; ISH (In Situ Hybridization); IHC (Immunohistochemistry); IF (Immunofluorescence); Nuclear-Cytoplasmic Fractionation; RIP (RNA Immunoprecipitation); RNA Pull-Down; Co-IP; Transfection; CCK8; Colony Formation Assay; Transwell Assay; In Vivo Animal Model; Western Blot; Flow Cytometry（Non-apoptosis/cycle）; Cohort Study; Survival Analysis; Bioinformatics Analysis |
| Clinical significance: |
High circCCNY expression correlates with better overall survival and recurrence-free survival; low circCCNY expression is associated with lenvatinib resistance; circCCNY may serve as a biomarker for predicting HCC sensitivity to lenvatinib and as a therapeutic target. |
| Description: |
circCCNY/hsa_circ_0000235 is downregulated in HCC tissues and lenvatinib-resistant HCC cells, and higher expression is associated with favorable survival. Functionally, circCCNY suppresses tumor progression and lenvatinib resistance while promoting antitumor immune activity. Mechanistically, it scaffolds the HSP60/SMURF1 complex to promote HSP60 ubiquitination and degradation, thereby inhibiting MAPK and HSP60/MAPK/c-Myc/PD-L1 signaling. |
| Confidence score: |
0.8949 |