| Expression pattern: |
UP |
| Associated gene: |
WTAP, METTL3, METTL14, SOX9, YTHDF2 |
| Associated microRNA: |
- |
| Biological function: |
Promotes rheumatoid arthritis progression; inhibits chondrocyte proliferation, migration and anabolism; promotes chondrocyte apoptosis and catabolism; regulates chondrocyte metabolic balance. |
| Molecular mechanism: |
circFTO binds and facilitates assembly of the WTAP/METTL3/METTL14 m6A methyltransferase complex, increasing global m6A and enhancing m6A modification on SOX9 3’UTR, leading to reduced SOX9 mRNA stability; YTHDF2 mediates SOX9 mRNA degradation in an m6A-dependent manner. |
| Biological pathway or process: |
m6A modification (promotes); mRNA stability (inhibits); apoptosis (promotes); proliferation (inhibits); migration (inhibits); other pathway/process (other) |
| Detected method: |
Q
S
|
| Validation methods: |
RNA-seq; RT-qPCR; RNase R Treatment; Actinomycin D / DRB Stability Assay; FISH / smFISH; RNA Pull-Down; RIP (RNA Immunoprecipitation); Co-IP; Transfection; CCK8; Transwell Assay; TUNEL; Western Blot; In Vivo Animal Model; H&E Staining; Bioinformatics Analysis; Clinical Sample Validation |
| Clinical significance: |
Increased expression of circFTO in synovial tissues from patients with RA; circFTO suggested as a therapeutic target for RA. |
| Description: |
Exosomal circFTO derived from RA fibroblast-like synoviocytes is up-regulated in RA and aggravates disease by impairing chondrocyte proliferation/migration and anabolic activity while promoting apoptosis and catabolism. Mechanistically, circFTO interacts with and promotes assembly of the WTAP/METTL3/METTL14 m6A writer complex, increasing m6A on SOX9 mRNA and reducing SOX9 mRNA stability via YTHDF2-dependent decay. circFTO knockdown alleviates arthritis phenotypes in the CIA mouse model. |
| Confidence score: |
0.8354 |