| Expression pattern: |
UP |
| Associated gene: |
NCL, TRIM21, p53, E cadherin |
| Associated microRNA: |
- |
| Biological function: |
promotes HCC invasion and migration/metastasis; affects EMT; stabilizes NCL protein |
| Molecular mechanism: |
circ0006646 binds NCL and prevents TRIM21-NCL interaction, reducing K48-linked polyubiquitination and proteasome-mediated degradation of NCL; downstream NCL represses p53 translation via binding TP53 5′UTR, affecting E-cadherin/EMT and metastasis |
| Biological pathway or process: |
metastasis (promotes); migration (promotes); invasion (promotes); EMT (promotes); p53 signaling (inhibits); ubiquitination (inhibits) |
| Detected method: |
Q
H
S
|
| Validation methods: |
RNA-seq; RT-qPCR; Back-Splice Junction PCR / divergent primers PCR; Sanger Sequencing; RNase R Treatment; Actinomycin D / DRB Stability Assay; FISH / smFISH; Nuclear-Cytoplasmic Fractionation; ISH (In Situ Hybridization); Clinical Sample Validation; Transfection; CCK8; Transwell Assay; Wound Healing Assay; RNA Pull-Down; RIP (RNA Immunoprecipitation); Western Blot; Co-IP; IF (Immunofluorescence); In Vivo Animal Model; H&E Staining; IHC (Immunohistochemistry); Bioinformatics Analysis; Cohort Study; Survival Analysis |
| Clinical significance: |
higher expression of circ0006646 was associated with higher TNM staging; elevated expression of circ0006646 was related to worse overall survival; overexpression of circ0006646 was an independent risk factor for HCC survival |
| Description: |
circ0006646 is up-regulated in HCC and promotes invasion/migration and metastasis. It binds NCL and blocks TRIM21-mediated K48-linked polyubiquitination, stabilizing NCL protein; stabilized NCL suppresses p53 translation and reduces E-cadherin, facilitating EMT and metastasis. High circ0006646 is associated with advanced TNM stage and poorer overall survival, and its knockdown shows therapeutic potential in xenograft/PDX models. |
| Confidence score: |
0.8988 |