| Expression pattern: |
UP |
| Associated gene: |
YBX3, ZO-1, YBX1, PCNA, p21, EIF4A3 |
| Associated microRNA: |
- |
| Biological function: |
promotes MSC senescence and cell cycle arrest; impairs proliferation and clonal expansion; promotes SASP expression; contributes to cartilage degeneration in aging-related OA |
| Molecular mechanism: |
circSERPINE2 binds YBX3 and promotes its cytoplasmic sequestration via enhancing YBX3-ZO-1 interaction, reducing YBX3 binding to the PCNA promoter, decreasing PCNA transcription and chromatin-bound PCNA, and thereby inhibiting p21 ubiquitin-mediated degradation through the ubiquitin-proteasome pathway; EIF4A3 downregulation increases circSERPINE2 production |
| Biological pathway or process: |
cell cycle (promotes); proliferation (inhibits); apoptosis (not specified); ubiquitination (promotes); mRNA stability (not specified); ceRNA regulation (not specified) |
| Detected method: |
Q
S
|
| Validation methods: |
RNA-seq; RT-qPCR; divergent primers PCR; Sanger Sequencing; RNase R Treatment; Actinomycin D / DRB Stability Assay; FISH / smFISH; Nuclear-Cytoplasmic Fractionation; RNA Pull-Down; RIP (RNA Immunoprecipitation); Co-IP; Luciferase Reporter Assay; Transfection; EdU Staining; Colony Formation Assay; Cell Cycle Assay; IF (Immunofluorescence); Western Blot; In Vivo Animal Model; Micro-CT; H&E Staining; ISH (In Situ Hybridization); Clinical Sample Validation; Bioinformatics Analysis |
| Clinical significance: |
circSERPINE2 was significantly increased in the synovium of OA patients; si-circSerpine2 showed therapeutic potential in mice with aging-related OA |
| Description: |
circSERPINE2 (hsa_circ_0005773) is up-regulated during MSC senescence and in OA patient synovium. It promotes MSC senescence by binding YBX3 and facilitating its cytoplasmic retention via ZO-1, which suppresses PCNA transcription and reduces PCNA-dependent ubiquitin-proteasome degradation of p21. In aged mice, intra-articular si-circSerpine2 alleviates joint-resident MSC senescence and cartilage degeneration in aging-related OA. |
| Confidence score: |
0.8637 |