| Expression pattern: |
UP |
| Associated gene: |
FTO, METTL14, NRF2, FTMT, ABCB8, Bax, Bcl-2 |
| Associated microRNA: |
- |
| Biological function: |
circ-ZNF609 knockdown protects against DOX-induced cardiotoxicity by attenuating cardiomyocyte apoptosis, reducing ROS accumulation, and ameliorating mitochondrial nonheme iron overload; circ-ZNF609 negatively regulates FTO in this context. |
| Molecular mechanism: |
m6A modification regulates circ-ZNF609 stability; circ-ZNF609 knockdown decreases total RNA m6A level in DOX-treated hearts and upregulates FTO by inhibiting Fto mRNA degradation, thereby reducing apoptosis/oxidative stress and mitochondrial iron overload. |
| Biological pathway or process: |
apoptosis (inhibits); oxidative phosphorylation (other); mitochondrial function (promotes); ferroptosis (inhibits); inflammation (not specified); m6A modification (other) |
| Detected method: |
Q
|
| Validation methods: |
RT-qPCR; Actinomycin D / DRB Stability Assay; Dot Blot; Transfection; TUNEL; Western Blot; In Vivo Animal Model; IF (Immunofluorescence); H&E Staining |
| Clinical significance: |
circ-ZNF609 inhibition represents a potential therapy for DOX-induced cardiotoxicity. |
| Description: |
In DOX-induced cardiotoxicity models, circ-ZNF609 is upregulated in cardiomyocytes. Silencing circ-ZNF609 protects the heart/cardiomyocytes by reducing apoptosis, oxidative stress, and mitochondrial nonheme iron overload, and it acts in part by upregulating FTO (via inhibiting Fto mRNA degradation) within an m6A-regulated circuit affecting circ-ZNF609 stability. |
| Confidence score: |
0.5699 |