circVEGFA inhibits apoptosis in porcine ovarian granulosa cells by binding to miR-21-3p and up-regulating TMX4 expression.

BACKGROUND: Follicular atresia is a major determinant of ovarian failure in multiparous sows. Non-coding RNAs (ncRNAs) play an important role in the regulatory mechanisms controlling apoptosis within ovarian granulosa cells (GCs). METHODS: The circular structure of circVEGFA was validated by RNase R and actinomycin D treatments. The function of circVEGFA during apoptosis in GCs was investigated by si-RNA transfection. Furthermore, competitive binding of circVEGFA and TMX4 to miR-21-3p was confirmed by a dual-luciferase reporter gene assay and co-transfection with their inhibitors or siRNA. RESULTS: In this study, we present a novel circular RNA (circRNA), circVEGFA, which shows significantly reduced expression in atretic follicles (AFs) compared to healthy follicles (HFs). CONCLUSIONS: The study demonstrates that circVEGFA increases TMX4 expression and inhibits apoptosis in GCs through competitive binding to miR-21-3p. This study contributes to the understanding of circRNA regulation after follicular atresia.