| Expression pattern: |
DN |
| Associated gene: |
FOXO1, FTO |
| Associated microRNA: |
miR-642a-5p |
| Biological function: |
attenuates oxidative stress-induced mitochondrial dysfunction and cellular senescence/apoptosis in granulosa cells; protects ovarian function and fertility in POI models |
| Molecular mechanism: |
FTO-mediated m6A demethylation increases circBRCA1 stability/expression; exosomal circBRCA1 functions as a ceRNA sponge of miR-642a-5p to upregulate FOXO1 |
| Biological pathway or process: |
mitochondrial function (promotes); apoptosis (inhibits); cell cycle (inhibits); ceRNA regulation (promotes) |
| Detected method: |
Q
|
| Validation methods: |
RT-qPCR; RNase R Treatment; Sanger Sequencing; Back-Splice Junction PCR / divergent primers PCR; Actinomycin D / DRB Stability Assay; FISH / smFISH; Nuclear-Cytoplasmic Fractionation; MeRIP / MeRIP-seq; Luciferase Reporter Assay; RNA Pull-Down; Transfection; Western Blot; In Vivo Animal Model; TUNEL; IF (Immunofluorescence); IHC (Immunohistochemistry); TEM |
| Clinical significance: |
circBRCA1 is decreased in serum and GCs of POI patients, correlates with ovarian reserve indicators, and is expected to be a novel biological marker for POI |
| Description: |
circBRCA1 (hsa_circ_0043949), derived from BRCA1 and enriched in HucMSC exosomes, is down-regulated in serum and granulosa cells of POI patients. Exosomal circBRCA1 alleviates oxidative stress-induced granulosa cell mitochondrial dysfunction and senescence by acting as a ceRNA that sponges miR-642a-5p, thereby upregulating FOXO1; its stability/expression is enhanced by FTO-mediated m6A demethylation. Clinically, circBRCA1 correlates with ovarian reserve indicators and is proposed as a potential biomarker/therapeutic target for POI. |
| Confidence score: |
0.8435 |