| Expression pattern: |
UP |
| Associated gene: |
CBL, LMO7, MST1, YAP, CCNA2, CCNH, CCND1 |
| Associated microRNA: |
- |
| Biological function: |
inhibits osteogenesis, promotes adipogenesis, and inhibits proliferation of BMSCs in senile osteoporosis; ASO knockdown promotes bone formation in aged mice |
| Molecular mechanism: |
circSTX12 binds CBL to reduce ubiquitination-mediated degradation of MST1, activates Hippo pathway and inhibits YAP nuclear translocation to shift BMSC fate toward adipogenesis and away from osteogenesis; circSTX12 binds and sequesters LMO7 in cytoplasm, reducing transcription of CCNA2/CCNH/CCND1 to inhibit proliferation |
| Biological pathway or process: |
Hippo/YAP (promotes); osteogenesis (inhibits); adipogenesis (promotes); proliferation (inhibits); ubiquitination (inhibits) |
| Detected method: |
Q
H
|
| Validation methods: |
divergent primers PCR; Back-Splice Junction PCR; Sanger Sequencing; RNase R Treatment; RT-qPCR; Nuclear-Cytoplasmic Fractionation; FISH / smFISH; RNA Pull-Down; Bioinformatics Analysis; Western Blot; RIP (RNA Immunoprecipitation); Co-IP; Transfection; CCK8; EdU Staining; Colony Formation Assay; Cell Cycle Assay; In Vivo Animal Model; H&E Staining; IHC (Immunohistochemistry); IF (Immunofluorescence); ROC Analysis; CUT&Tag sequencing and analysis |
| Clinical significance: |
circSTX12 is increased in bone tissues/BMSCs from osteopenia/osteoporotic patients and ROC analysis was performed to evaluate diagnostic ability of gene expression |
| Description: |
circSTX12 is up-regulated in senile osteoporosis bone/BMSCs and shifts BMSC fate toward adipogenesis while suppressing osteogenesis and proliferation. Mechanistically, it binds CBL to inhibit MST1 ubiquitination/degradation, activating Hippo signaling and limiting YAP nuclear signaling during differentiation, and it sequesters LMO7 in the cytoplasm to reduce CCNA2/CCNH/CCND1 transcription and inhibit proliferation. ASO-mediated knockdown of circStx12 improves bone formation in aged mice. |
| Confidence score: |
0.8839 |