| Expression pattern: |
DN |
| Associated gene: |
AGO2, SIRT6, BIRC5 (Survivin), ATP2A2 (SERCA2a) |
| Associated microRNA: |
miR-330-5p |
| Biological function: |
CircITCH ameliorates doxorubicin-induced cardiomyocyte injury and dysfunction, reduces cellular/mitochondrial oxidative stress and DNA damage, inhibits cell death, improves contractile function and calcium handling, and partly prevents DOXIC in mice. |
| Molecular mechanism: |
CircITCH acts as an endogenous sponge of miR-330-5p, thereby upregulating SIRT6, BIRC5 (Survivin), and ATP2A2 (SERCA2a) through a ceRNA mechanism. |
| Biological pathway or process: |
ceRNA regulation (other); apoptosis (inhibits); mitochondrial function (promotes); fibrosis (inhibits); other pathway/process (inhibits); drug resistance (other) |
| Detected method: |
Q
B
H
S
|
| Validation methods: |
Back-Splice Junction PCR / divergent primers PCR; RNase R Treatment; Sanger Sequencing; circRNA-seq; RT-qPCR; Northern Blot; FISH / smFISH; ISH (In Situ Hybridization); Nuclear-Cytoplasmic Fractionation; Clinical Sample Validation; RIP (RNA Immunoprecipitation); RNA Pull-Down; Luciferase Reporter Assay; Bioinformatics Analysis; Transfection; CCK8; IF (Immunofluorescence); Western Blot; In Vivo Animal Model; H&E Staining |
| Clinical significance: |
CircITCH is downregulated in autopsy specimens from cancer patients with DOX-induced cardiomyopathy and represents a potential therapeutic target for DOXIC. |
| Description: |
CircITCH (hsa_circ_0001141), an ITCH-derived human circRNA, is downregulated in DOX-induced cardiotoxicity. It protects cardiomyocytes and mouse hearts from DOXIC by sponging miR-330-5p and relieving repression of SIRT6, BIRC5/Survivin, and ATP2A2/SERCA2a, thereby reducing oxidative stress, DNA damage and cell death while improving contractile function and calcium handling. |
| Confidence score: |
0.8581 |