| Expression pattern: |
UP |
| Associated gene: |
FUS, EP300, SLC7A11 promoter, SLC7A11 |
| Associated microRNA: |
- |
| Biological function: |
Promotes hypoxia-induced ferroptosis in human pulmonary arterial smooth muscle cells and promotes pulmonary vascular remodeling in pulmonary hypertension. |
| Molecular mechanism: |
ca-circSCN8A recruits EP300 to promote FUS lactylation, forms a ca-circSCN8A/FUS/EP300 complex through liquid-liquid phase separation, and forms an R-loop with the nonhost SLC7A11 promoter to repress SLC7A11 transcription and disrupt redox homeostasis. |
| Biological pathway or process: |
ferroptosis (promotes); other pathway/process (promotes) |
| Detected method: |
Q
|
| Validation methods: |
Back-Splice Junction PCR / divergent primers PCR; RNase R Treatment; Sanger Sequencing; RT-qPCR; FISH / smFISH; IF (Immunofluorescence); RIP (RNA Immunoprecipitation); RNA Pull-Down; Co-IP; ChIP / ChIP-seq; Transfection; In Vivo Animal Model; H&E Staining; Western Blot; Bioinformatics Analysis |
| Clinical significance: |
ca-circSCN8A is highlighted as a potential therapeutic target for pulmonary hypertension. |
| Description: |
ca-circSCN8A is up-regulated in pulmonary hypertension-related hypoxic conditions and promotes HPASMC ferroptosis and pulmonary vascular remodeling. Mechanistically, it recruits EP300 and FUS to form LLPS-associated nuclear condensates, stabilizes an R-loop at the nonhost SLC7A11 promoter, represses SLC7A11 transcription, disrupts redox homeostasis, and thereby enhances ferroptosis. |
| Confidence score: |
0.8067 |