| Expression pattern: |
UP |
| Associated gene: |
G3BP1, DDX3X, BRCA1, Brca1, NF-kappaB |
| Associated microRNA: |
- |
| Biological function: |
Promotes pro-inflammatory macrophage polarization, stress granule formation, inflammatory signalling, pro-inflammatory cytokine secretion, fibroblast activation, fibrosis, and adverse cardiac remodelling after MI; inhibition promotes anti-inflammatory macrophage polarization, improves cardiac function, reduces inflammation and fibrosis, and supports cardiac healing. |
| Molecular mechanism: |
circHIPK2 physically interacts with G3BP1 to promote stress granule formation and activate downstream inflammatory cascades including NF-kappaB signalling; BRCA1/Brca1 promotes circHIPK2 biogenesis independently of the host gene. |
| Biological pathway or process: |
inflammation (promotes); immune regulation (promotes); macrophage polarization (other); fibrosis (promotes); NF-kappaB (promotes); autophagy (inhibits); apoptosis (promotes); migration (promotes); oxidative phosphorylation (other); other pathway/process (promotes) |
| Detected method: |
Q
S
|
| Validation methods: |
Back-Splice Junction PCR / divergent primers PCR; RNase R Treatment; Sanger Sequencing; Actinomycin D / DRB Stability Assay; RT-qPCR; RNA-seq; FISH / smFISH; IF (Immunofluorescence); Nuclear-Cytoplasmic Fractionation; Clinical Sample Validation; RIP (RNA Immunoprecipitation); RNA Pull-Down; Luciferase Reporter Assay; Transfection; Wound Healing Assay; TUNEL; In Vivo Animal Model; H&E Staining; IHC (Immunohistochemistry); Western Blot; Bioinformatics Analysis |
| Clinical significance: |
circHIPK2 is highly expressed in cardiac tissues and PBMCs from heart failure patients, elevated in ICM tissue, associated with inflammatory gene signatures, and proposed as a promising therapeutic target for MI, inflammatory cardiac conditions, and heart failure. |
| Description: |
circHIPK2 is a HIPK2-derived circRNA upregulated in inflammatory cardiac macrophages after MI and in human HF/ICM-related samples. It promotes pro-inflammatory macrophage polarization by interacting with G3BP1 to facilitate stress granule formation and downstream NF-kappaB-linked inflammatory signalling. Macrophage-specific circHIPK2 inhibition reduces inflammation, cytokine secretion, fibroblast activation and fibrosis, improves post-MI cardiac function, and shows translational therapeutic potential in human myocardial slice co-culture models. |
| Confidence score: |
0.8816 |