| Expression pattern: |
DN |
| Associated gene: |
valosin-containing protein (VCP), Med12 |
| Associated microRNA: |
- |
| Biological function: |
Inhibits diabetic cardiomyopathy progression and suppresses diabetic cardiomyocyte pyroptosis; DICAR deficiency induces cardiac dysfunction, hypertrophy and fibrosis, while DICAR overexpression alleviates these phenotypes. |
| Molecular mechanism: |
DICAR binds VCP via its junction domain, modulating VCP function and thereby regulating VCP-mediated Med12 protein degradation through the ubiquitin-proteasome pathway, which affects cardiomyocyte pyroptosis. |
| Biological pathway or process: |
pyroptosis (inhibits); apoptosis (other); other pathway/process (other) |
| Detected method: |
Q
M
|
| Validation methods: |
Microarray; Bioinformatics Analysis; RNase R Treatment; RT-qPCR; Back-Splice Junction PCR / divergent primers PCR; Sanger Sequencing; FISH / smFISH; Transfection; RIP (RNA Immunoprecipitation); RNA Pull-Down; Western Blot; Co-IP; In Vivo Animal Model; IHC (Immunohistochemistry); H&E Staining |
| Clinical significance: |
DICAR levels in PBMCs and plasma are decreased in T2DM patients versus healthy controls; proposed as a biomarker for diabetes and a potential nucleic-acid drug candidate for DCM. |
| Description: |
DICAR (mm9_circ_008009; conserved human hsa_circ_0131202) is down-regulated in diabetic hearts and in AGEs-treated cardiomyocytes and protects against diabetic cardiomyopathy by inhibiting cardiomyocyte pyroptosis. Mechanistically, DICAR binds VCP via its junction domain, affecting VCP-mediated ubiquitin-proteasome degradation of Med12, thereby modulating pyroptosis; circulating DICAR in PBMCs/plasma is reduced in T2DM patients and may serve as a biomarker/therapeutic candidate. |
| Confidence score: |
0.8462 |