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miRNA-21-3p targeting of FGF2 suppresses autophagy of bovine ovarian granulosa cells through AKT/mTOR pathway.

It is widely thought that the main reason for ovarian follicular atresia is apoptosis of granulosa cells, however, accumulating evidence suggests that autophagy plays a role in the fate of… Click to show full abstract

It is widely thought that the main reason for ovarian follicular atresia is apoptosis of granulosa cells, however, accumulating evidence suggests that autophagy plays a role in the fate of granulosa cells. Although epigenetic regulation including miR-21-3p associated with autophagy process has been reported in many cancer types, nevertheless, the mechanism of miR-21-3p in bovine ovary is poorly understood. In the present study, bovine ovarian granulosa cells (BGCs) were used as a model to elucidate the autophagy and role of miR-21-3p in a cattle ovary. The results from gene expression and tagged autophagosomes showed the autophagy in BGCs and miR-21-3p was identified as an important miRNA regulating autophagy of BGCs. The current results indicated that FGF2 was a validated target of miR-21-3p in autophagy regulation of BGCs according to the results from FGF2 luciferase reporter assays and FGF2 overexpression (oe-FGF2) or small interference (si-FGF2). Transfection of miR-21-3p mimic and si-FGF2 plasmids resulted in decreasing phosphorylated AKT and mTOR, while transfection of miR-21-3p inhibitor and oe-FGF2 increased the phosphorylated level of AKT and mTOR in BGCs. These data indicate that regulation of miR-21-3p on BGCs autophagy through AKT/mTOR pathway. In summary, this study suggests that miR-21-3p targets FGF2 to inhibit BGCs autophagy by repressing AKT/mTOR signaling.

Keywords: bovine ovarian; granulosa cells; mir; akt mtor

Journal Title: Theriogenology
Year Published: 2020

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