| Expression pattern: |
UP |
| Associated gene: |
BRPF3, KAT7, U2AF2 |
| Associated microRNA: |
- |
| Biological function: |
promotes fibrosis-related markers expression and promotes cardiac fibroblast proliferation and migration, exacerbating cardiac fibrosis |
| Molecular mechanism: |
circ-CELF1 binds BRPF3 to inhibit ubiquitin-proteasomal degradation, promotes BRPF3 nuclear translocation and recruitment of KAT7, increases H3K14ac at Celf1 promoter to activate Celf1 transcription and feedback enhances circ-CELF1 biogenesis, with downstream suppression of Smad7 |
| Biological pathway or process: |
fibrosis (promotes); proliferation (promotes); migration (promotes); other pathway/process (promotes) |
| Detected method: |
Q
|
| Validation methods: |
RT-qPCR; RNase R Treatment; Sanger Sequencing; FISH / smFISH; Nuclear-Cytoplasmic Fractionation; Clinical Sample Validation; RIP (RNA Immunoprecipitation); RNA Pull-Down; Transfection; EdU Staining; Wound Healing Assay; Western Blot; IF (Immunofluorescence); Co-IP; ChIP / ChIP-seq; In Vivo Animal Model; H&E Staining; IHC (Immunohistochemistry) |
| Clinical significance: |
potential diagnostic biomarker and therapeutic target for cardiac fibrosis |
| Description: |
circ-CELF1 is up-regulated in mouse MI/TGF-beta1 cardiac fibrosis models and promotes fibroblast activation, proliferation and migration, thereby aggravating fibrosis. It binds BRPF3 to inhibit its ubiquitin-proteasomal degradation and enhance nuclear BRPF3, which recruits KAT7 to increase H3K14ac at the Celf1 promoter, activating Celf1 transcription and forming a positive feedback loop that boosts circ-CELF1 biogenesis while suppressing Smad7. |
| Confidence score: |
0.8586 |