| Expression pattern: |
DN |
| Associated gene: |
CPSF6 |
| Associated microRNA: |
miR-17-5p, miR-93-5p |
| Biological function: |
sponges AD-relevant miRNAs and sequesters AD-associated RBP CPSF6; circGigyf2 deficiency potentiates neuronal apoptotic responses upon insults |
| Molecular mechanism: |
ceRNA-like miRNA sponging (miR-17-5p/miR-93-5p) increasing their silencing activity when circGigyf2 is reduced; RBP sequestration of CPSF6 affecting proximal polyadenylation site processing efficiency of CPSF6 targets |
| Biological pathway or process: |
ceRNA regulation (promotes); apoptosis (inhibits) |
| Detected method: |
Q
S
|
| Validation methods: |
RNase R Treatment; RNA-seq; Bioinformatics Analysis; RT-qPCR; divergent primers PCR; RNA Pull-Down; Western Blot; Transfection; In Vivo Animal Model; TUNEL |
| Clinical significance: |
circGIGYF2 levels in AD patients’ cortices are negatively correlated with dementia severity (clinical dementia rating) in BM36 and BM44 |
| Description: |
circGigyf2/circGIGYF2 is progressively down-regulated at the irreversible progression stage of AD in 5xFAD mouse cortex and in specific human AD subcortical regions, correlating with dementia severity. Its reduction releases sponged miR-17-5p/miR-93-5p and CPSF6, enhancing miRNA silencing and CPSF6-mediated proximal polyadenylation, which promotes vulnerability to neuronal apoptosis. |
| Confidence score: |
0.717 |