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 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 miR21-3p 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. (C) 2020 Elsevier Inc. All rights reserved.