| Expression pattern: |
DN |
| Associated gene: |
SphK1, STAT3 |
| Associated microRNA: |
miR-124, miR-152, miR-338 |
| Biological function: |
circHIPK3 protects human osteoblasts from DEX-induced cytotoxicity by suppressing apoptosis, programmed necrosis, mitochondrial depolarization, CyPD-ANT-1 association, and cytochrome C cytosol release; circHIPK3 knockdown enhances DEX-induced cytotoxicity. |
| Molecular mechanism: |
DEX downregulates circHIPK3, causing miR-124 accumulation and downregulation of the pro-survival miR-124 targets SphK1 and STAT3; circHIPK3 overexpression reduces miR-124 levels and attenuates DEX-induced cell death. |
| Biological pathway or process: |
apoptosis (inhibits); mitochondrial function (promotes); ceRNA regulation (other); other pathway/process (inhibits) |
| Detected method: |
Q
|
| Validation methods: |
RT-qPCR; Clinical Sample Validation; Transfection; MTT; ELISA; Annexin V/PI Flow Cytometry; Western Blot |
| Clinical significance: |
circHIPK3 levels are reduced in human necrotic femoral head tissues from DEX-taking patients, suggesting a potential protective target for DEX-associated osteoblast injury and osteonecrosis. |
| Description: |
This study shows that human circHIPK3 is downregulated by DEX in human osteoblasts and decreased in necrotic femoral head tissues from DEX-taking patients. Functionally, circHIPK3 overexpression protects osteoblasts from DEX-induced apoptosis and programmed necrosis, whereas circHIPK3 knockdown worsens cytotoxicity. Mechanistically, circHIPK3 downregulation promotes miR-124 accumulation and reduction of pro-survival targets SphK1 and STAT3, defining a circHIPK3-miR-124-related protective cascade. |
| Confidence score: |
0.5414 |