miR-7 promotes apoptosis and autophagy of granulosa cells by targeting KLF4 via JAK/STAT3 signaling pathway in chickens

Abstract

Granulosa cell (GC) death, which leads to follicular atresia, primarily occurs through apoptosis and autophagy. miRNAs are known to be key regulators of autophagy and apoptosis. Although miR-7 acting as a key regulator of follicular atresia, its precise role in granulosa cell autophagy and apoptosis remains to be fully elucidated. In this study, we found that miR-7 was highly expressed in the follicle based on qPCR analysis. Subsequently, transfection of miR-7 inhibitors and mimics downregulated or upregulated the expression of miR-7 and promoted autophagic and apoptotic processes in chicken follicle granulosa cells. Mechanistically, through dual-luciferase reporter gene assays, we validated that KLF4 is a target gene of miR-7. Contrarily, KLF4 was found to negatively regulate autophagy and apoptosis in follicular granulosa cells as evidenced by genetic intervention of KLF4 silencing and overexpression. Furthermore, JAK/STAT3 signaling pathway was confirmed to mediate the regulation of miR-7-KLF4 axis on GC autophagy and apoptosis. These findings offer evidences of the crucial involvement of the miR-7-KLF4 signaling axis in determining autophagy and apoptosis of GCs. This study could offer an important theoretical basis for the use of molecular-assisted breeding in chickens.