| Expression pattern: |
UP |
| Associated gene: |
CD39, ENTPD1, CD73 |
| Associated microRNA: |
miR-488-3p, miR-1298 |
| Biological function: |
promotes immunosuppressive microenvironment, induces M2-like macrophage polarization, impairs CD8+ T cell function, and confers anti-PD1 resistance in HCC |
| Molecular mechanism: |
exosomal circTMEM181 sponges miR-488-3p to upregulate CD39 (ENTPD1) in macrophages, cooperating with tumor-cell CD73 to activate the ATP-adenosine pathway and drive anti-PD1 resistance |
| Biological pathway or process: |
immune regulation (promotes); other pathway/process (promotes); apoptosis (not specified) |
| Detected method: |
Q
H
S
|
| Validation methods: |
RNA-seq; RT-qPCR; Sanger Sequencing; Back-Splice Junction PCR / divergent primers PCR; ISH (In Situ Hybridization); FISH / smFISH; RIP (RNA Immunoprecipitation); RNA Pull-Down; Luciferase Reporter Assay; Transfection; Flow Cytometry（Non-apoptosis/cycle）; IHC (Immunohistochemistry); In Vivo Animal Model; Western Blot; ELISA; Survival Analysis; Bioinformatics Analysis |
| Clinical significance: |
elevated circTMEM181 is associated with poor response to anti-PD1 therapy and is related to short overall survival and early recurrence after operation in HCC patients |
| Description: |
circTMEM181 is up-regulated in HCC, especially in anti-PD1-resistant patients, and high expression predicts poor prognosis. HCC cells secrete exosomal circTMEM181, which sponges miR-488-3p in macrophages to increase CD39 (ENTPD1), cooperating with tumor-cell CD73 to activate the ATP-adenosine pathway, suppress CD8+ T cell function, and drive anti-PD1 resistance. |
| Confidence score: |
0.8652 |