| Expression pattern: |
UP |
| Associated gene: |
PARP1, IL1B, IL1beta, PD-L1 |
| Associated microRNA: |
- |
| Biological function: |
circADAMTS12 promotes breast cancer metastatic colonization in the brain, protects cancer cells from microglia-mediated cytotoxic killing and phagocytosis, induces microglial anti-inflammatory M2-like polarization, upregulates inflammatory cytokine/chemokine expression including IL1B/IL1beta, and increases PD-L1 expression in cancer cells and microglia to suppress antitumor immunity. |
| Molecular mechanism: |
circADAMTS12 binds and activates PARP1 in cancer cells, increasing PARylation and IL1B/IL1beta expression; IL1beta-containing conditioned medium promotes microglial M2-like polarization, while circADAMTS12 also upregulates PD-L1 in cancer cells and microglia to inhibit microglial phagocytosis and T-cell antitumor immunity. |
| Biological pathway or process: |
metastasis (promotes); macrophage polarization (promotes); immune regulation (inhibits); inflammation (promotes); other pathway/process (promotes) |
| 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; Clinical Sample Validation; RIP (RNA Immunoprecipitation); RNA Pull-Down; Transfection; Flow Cytometry（Non-apoptosis/cycle）; In Vivo Animal Model; ELISA; Western Blot; IHC (Immunohistochemistry); Survival Analysis; Bioinformatics Analysis |
| Clinical significance: |
Serum circADAMTS12 is elevated in patients with breast cancer with B2BM compared with patients without brain metastasis and is proposed as a potential biomarker and immunotherapy target for B2BM. |
| Description: |
circADAMTS12 is an upregulated oncogenic circRNA in breast-to-brain metastasis. It binds and activates PARP1 to induce IL1B/IL1beta expression, promotes microglial M2-like polarization, upregulates PD-L1 in cancer cells and microglia, and suppresses microglia- and T-cell-mediated antitumor immunity. Targeting circADAMTS12 reduces brain metastatic colonization and can synergize with PD-L1 blockade in immunocompetent mouse models. |
| Confidence score: |
0.8769 |