| Expression pattern: |
DN |
| Associated gene: |
YTHDF2, RAB22A, PI3K |
| Associated microRNA: |
- |
| Biological function: |
Protects against chondrocyte senescence and alleviates osteoarthritis progression by promoting autophagy; circHIPK2 depletion exacerbates senescence and cartilage degeneration. |
| Molecular mechanism: |
m6A-dependent YTHDF2-mediated decay reduces circHIPK2 stability; circHIPK2 directly binds RAB22A to disrupt RAB22A-PI3K association, inhibiting PI3K-AKT-mTOR signaling and restoring autophagic flux. |
| Biological pathway or process: |
PI3K/AKT/mTOR (inhibits); autophagy (promotes); cellular senescence (inhibits); proliferation (other) |
| Detected method: |
Q
H
S
|
| Validation methods: |
RNA-seq; RT-qPCR; FISH / smFISH; Nuclear-Cytoplasmic Fractionation; Back-Splice Junction PCR / divergent primers PCR; RNase R Treatment; Sanger Sequencing; Actinomycin D / DRB Stability Assay; Clinical Sample Validation; Transfection; Western Blot; RIP (RNA Immunoprecipitation); MeRIP / MeRIP-seq; RNA Pull-Down; Bioinformatics Analysis; In Vivo Animal Model; IHC (Immunohistochemistry); IF (Immunofluorescence); Flow Cytometry（Non-apoptosis/cycle）; Cell Cycle Assay; TUNEL; H&E Staining |
| Clinical significance: |
Potential therapeutic target and prognostic biomarker for cartilage aging in OA. |
| Description: |
circHIPK2 is down-regulated in osteoarthritis cartilage and acts as a chondroprotective circRNA. YTHDF2 recognizes m6A-modified circHIPK2 and promotes its degradation, weakening circHIPK2-RAB22A binding, enhancing RAB22A-PI3K interaction, activating PI3K-AKT-mTOR signaling, impairing autophagy, and accelerating chondrocyte senescence; restoring circHIPK2 (AAV or LNP delivery) alleviates OA progression in DMM mice. |
| Confidence score: |
0.8817 |