| Expression pattern: |
UP |
| Associated gene: |
KLF6, DNMT1/3a, NLRP3, Klotho |
| Associated microRNA: |
miR-124-3p, miR-148b-3p |
| Biological function: |
circHIPK3 aggravates SAKI inflammatory responses, promotes NLRP3/caspase-1-mediated pyroptosis, accelerates cell senescence, and worsens kidney injury; circHIPK3 silencing alleviates kidney injury, inflammation, and senescence and enhances HK-2 cell viability. |
| Molecular mechanism: |
circHIPK3 functions as a cytoplasmic ceRNA that competitively binds miR-124-3p to upregulate KLF6 and activate NLRP3/caspase-1-mediated pyroptosis; it also binds miR-148b-3p to upregulate DNMT1/3a, increase Klotho promoter methylation, reduce Klotho expression, and accelerate cell senescence. |
| Biological pathway or process: |
ceRNA regulation (promotes); pyroptosis (promotes); inflammation (promotes); other pathway/process (promotes) |
| Detected method: |
Q
|
| Validation methods: |
RNase R Treatment; RT-qPCR; Clinical Sample Validation; ELISA; Transfection; CCK8; Western Blot; In Vivo Animal Model; H&E Staining; Nuclear-Cytoplasmic Fractionation; RIP (RNA Immunoprecipitation); RNA Pull-Down; Luciferase Reporter Assay; ChIP / ChIP-seq; MSP (Methylation-Specific PCR); Bioinformatics Analysis |
| Clinical significance: |
circHIPK3 was elevated in serum of SAKI patients and correlated positively with TNF-alpha and IL-6 and negatively with IL-10, suggesting association with inflammatory status in SAKI. |
| Description: |
circHIPK3 is up-regulated in SAKI patient serum, SAKI mouse kidney tissues, and LPS-induced HK-2 cells. It aggravates SAKI inflammation through the miR-124-3p/KLF6/NLRP3/caspase-1 pyroptosis pathway and accelerates cell senescence through the miR-148b-3p/DNMT1/3a/Klotho promoter methylation axis. Silencing circHIPK3 protects against kidney injury, reduces inflammatory responses and senescence, and improves HK-2 cell viability. |
| Confidence score: |
0.8081 |