| Expression pattern: |
DN |
| Associated gene: |
CDK9, FUNDC1 promoter, FUNDC1 mRNAs, FUNDC1 protein |
| Associated microRNA: |
miR-5002-3p, miR-502-5p, miR-6778-3p |
| Biological function: |
Maintains extracellular matrix homeostasis in NPCs; promotes mitophagy; reduces ROS; inhibits cellular senescence; delays IVDD progression under oxidative stress |
| Molecular mechanism: |
Nuclear circFUNDC1 binds CDK9 and recruits it to the FUNDC1 promoter via complementary nucleotides to transactivate FUNDC1 transcription, increasing FUNDC1 mRNA/protein and promoting mitophagy (positive feedback loop). |
| Biological pathway or process: |
mitochondrial function (promotes); apoptosis (other); proliferation (other); ceRNA regulation (inhibits); fibrosis (other); oxidative phosphorylation (other); autophagy (promotes); senescence (inhibits); other pathway/process (other) |
| Detected method: |
Q
H
|
| Validation methods: |
RT-qPCR; FISH / smFISH; Back-Splice Junction PCR / divergent primers PCR; RNase R Treatment; Sanger Sequencing; Nuclear-Cytoplasmic Fractionation; Transfection; RNA Pull-Down; RIP (RNA Immunoprecipitation); Luciferase Reporter Assay; RNA-seq; Western Blot; IHC (Immunohistochemistry); IF (Immunofluorescence); In Vivo Animal Model; Bioinformatics Analysis; Flow Cytometry(Non-apoptosis/cycle); H&E Staining |
| Clinical significance: |
inverse correlation of circFUNDC1 levels with disease severity in clinical samples of IVDD; potential therapeutic target for IVDD |
| Description: |
circFUNDC1 is down-regulated in end-stage IVDD NPCs and predominantly nuclear. It binds CDK9 and recruits it to the FUNDC1 promoter to enhance FUNDC1 transcription/protein, promoting mitophagy, reducing ROS and senescence, and maintaining ECM anabolic factor expression, thereby delaying IVDD progression under oxidative stress. |
| Confidence score: |
0.8516 |