| Expression pattern: |
DN |
| Associated gene: |
hnRNPA2B1, ACSL4 mRNA, ACSL4, SETDB1, METTL14, H3K9me3 |
| Associated microRNA: |
- |
| Biological function: |
circSCYL2 suppresses breast cancer brain metastasis, inhibits cancer cell crossing of the blood-brain barrier, reduces brain metastatic burden, promotes ferroptosis, increases cancer cell death, and decreases tumor proliferation marker Ki67 in vivo. |
| Molecular mechanism: |
circSCYL2 competitively binds the m6A reader hnRNPA2B1, blocks hnRNPA2B1 recognition of m6A-modified ACSL4 mRNA and recruitment of SETDB1, reduces H3K9me3 at the ACSL4 promoter, enhances ACSL4 transcription, and promotes ferroptosis to inhibit brain metastasis. |
| Biological pathway or process: |
ferroptosis (promotes); metastasis (inhibits); proliferation (inhibits); migration (inhibits); m6A modification (other); other pathway/process (other) |
| Detected method: |
Q
|
| Validation methods: |
RT-qPCR; RNA-seq; Bioinformatics Analysis; Transfection; Transwell Assay; Flow Cytometry（Non-apoptosis/cycle）; RNA Pull-Down; Western Blot; RIP (RNA Immunoprecipitation); FISH / smFISH; IF (Immunofluorescence); MeRIP / MeRIP-seq; Luciferase Reporter Assay; Co-IP; ChIP / ChIP-seq; Nuclear-Cytoplasmic Fractionation; In Vivo Animal Model; H&E Staining |
| Clinical significance: |
circSCYL2 has potential as a biomarker for predicting the risk of brain metastasis in BC patients and as a therapeutic target for suppressing brain metastasis, but clinical validation remains required. |
| Description: |
circSCYL2 is downregulated in breast cancer cells from brain metastases. Its overexpression suppresses brain metastatic colonization and BBB crossing by promoting ACSL4-dependent ferroptosis. Mechanistically, circSCYL2 binds hnRNPA2B1 and disrupts m6A-dependent hnRNPA2B1/SETDB1-mediated H3K9me3 repression at the ACSL4 promoter, thereby enhancing ACSL4 transcription. |
| Confidence score: |
0.7233 |