| Expression pattern: |
UP |
| Associated gene: |
Sox9, AGO2, GRP78 |
| Associated microRNA: |
miR-616-5p, miR-508-5p, miR-561-5p, miR-328-5p, miR-761 |
| Biological function: |
promotes ECM synthesis (Collagen II, Aggrecan) and suppresses inflammatory cytokines (IL-1beta, TNF-alpha, PGE2) in NP cells, suggesting a protective role in IVDD |
| Molecular mechanism: |
ceRNA mechanism: circ-4099 sponges miR-616-5p to relieve inhibition of Sox9; TNF-alpha induces circ-4099 transcription via MAPK/NF-kappaB signaling and GRP78 |
| Biological pathway or process: |
NF-kappaB (promotes); MAPK (promotes); ceRNA regulation (promotes); inflammation (inhibits); other pathway/process (promotes) |
| Detected method: |
Q
M
|
| Validation methods: |
Microarray; RNase R Treatment; RT-qPCR; divergent primers PCR; Sanger Sequencing; FISH / smFISH; RIP (RNA Immunoprecipitation); RNA Pull-Down; Luciferase Reporter Assay; Transfection; ELISA; Western Blot; Bioinformatics Analysis; Nuclear-Cytoplasmic Fractionation; In Vivo Animal Model |
| Clinical significance: |
Circ-4099 may be a protective factor in IVD degeneration and a potential therapeutic target to restore NP cell function |
| Description: |
In IVDD, circ-4099 is upregulated in degenerated human NP tissues and is induced by TNF-alpha via MAPK/NF-kappaB-related signaling and GRP78-dependent transcriptional regulation. Functionally, circ-4099 acts as a cytoplasmic ceRNA that sponges miR-616-5p, relieving repression of Sox9 to enhance ECM components (Collagen II, Aggrecan) and reduce inflammatory mediators, suggesting a protective/compensatory role in disc degeneration. |
| Confidence score: |
0.8095 |