| Expression pattern: |
UP |
| Associated gene: |
ALKBH5, SLUG, CRM1, QKI, EGFR |
| Associated microRNA: |
- |
| Biological function: |
inhibits hypoxia-stimulated partial EndMT; inhibits angiogenesis and post-ischemic recovery; suppresses endothelial proliferation, migration and sprouting under hypoxia |
| Molecular mechanism: |
circATXN1 binds ALKBH5 and modulates its subcellular localization (prevents nuclear retention) via phosphorylation/CRM1 interaction, thereby altering m6A demethylation of pre-SLUG mRNA, reducing SLUG mRNA stability and inhibiting partial EndMT; not via miRNA sponge; does not encode peptides |
| Biological pathway or process: |
EMT (inhibits); angiogenesis (inhibits); migration (inhibits); proliferation (inhibits); m6A modification (other pathway/process); mRNA stability (inhibits) |
| Detected method: |
Q
S
|
| Validation methods: |
RNA-seq; RT-qPCR; RNase R Treatment; Back-Splice Junction PCR / divergent primers PCR; Sanger Sequencing; FISH / smFISH; Nuclear-Cytoplasmic Fractionation; RNA Pull-Down; RIP (RNA Immunoprecipitation); Co-IP; Luciferase Reporter Assay; Actinomycin D / DRB Stability Assay; MeRIP / MeRIP-seq; Transfection; CCK8; Transwell Assay; Tube Formation Assay; In Vivo Animal Model; H&E Staining; IF (Immunofluorescence); IHC (Immunohistochemistry); Survival Analysis; Clinical Sample Validation; Bioinformatics Analysis |
| Clinical significance: |
circATXN1 expression in peripheral blood exosomes is higher in patients with myocardial infarction and lower limb ischemia than controls, suggesting it may serve as a biomarker to predict disease progression/severity/prognosis in ischemic conditions |
| Description: |
circATXN1 is up-regulated in endothelial cells under ischemic/hypoxic conditions and in ischemic tissues, and is also elevated in peripheral blood exosomes of MI and lower limb ischemia patients. Functionally, circATXN1 restrains hypoxia-induced partial EndMT and angiogenesis, whereas circATXN1 knockdown promotes partial EndMT and improves post-ischemic vascular and cardiac recovery. Mechanistically, circATXN1 binds ALKBH5 to regulate its nuclear-cytoplasmic trafficking and m6A-dependent pre-SLUG mRNA stability, thereby controlling SLUG levels. |
| Confidence score: |
0.8987 |