| Expression pattern: |
UP |
| Associated gene: |
TIM-3, AGO2 |
| Associated microRNA: |
miR-449c-5p |
| Biological function: |
induces NK cell dysfunction/exhaustion, promotes immune evasion and HCC progression, and contributes to resistance to anti-PD1 therapy; inhibits NK cell-derived IFN-gamma and TNF-alpha secretion |
| Molecular mechanism: |
Exosomal circUHRF1 is transferred into NK cells, binds/sponges miR-449c-5p (AGO2-associated), leading to increased TIM-3 expression and NK cell exhaustion; associated with anti-PD1 resistance |
| Biological pathway or process: |
immune regulation (promotes); other pathway/process (promotes); ceRNA regulation (promotes) |
| Detected method: |
Q
|
| Validation methods: |
RT-qPCR; RNase R Treatment; Sanger Sequencing; circRIP; RIP (RNA Immunoprecipitation); RNA Pull-Down; Luciferase Reporter Assay; Transfection; ELISA; Western Blot; IHC (Immunohistochemistry); In Vivo Animal Model; Survival Analysis; Cohort Study; Clinical Sample Validation; Bioinformatics Analysis |
| Clinical significance: |
Increased circUHRF1 indicates poor clinical prognosis in HCC; plasma exosomal circUHRF1 is increased in HCC patients and associated with decreased NK cell proportion and decreased NK cell tumor infiltration; higher circUHRF1 correlates with resistance to anti-PD1 therapy |
| Description: |
circUHRF1 (hsa_circ_0048677), derived from UHRF1, is up-regulated in HCC tissues and enriched in HCC-cell-derived exosomes. It is transferred to NK cells and functions as a ceRNA to sequester/degrade miR-449c-5p, thereby increasing TIM-3 expression, inducing NK cell exhaustion, promoting immune evasion, and contributing to anti-PD1 therapy resistance. |
| Confidence score: |
0.8681 |