Attenuated AKT signaling by miR-146a-5p interferes with chicken granulosa cell proliferation, lipid deposition and progesterone biosynthesis.

Steroid hormones play a crucial role in the growth and maturation of poultry ovarian follicles, with progesterone secretion by granulosa cells (GC) being essential. According to our previous transcriptome analysis, it apparented that miR-146a-5p expressions were upregulated in the follicles undergoing atresia. In this study, we delved the depth to explore the underlying mechanisms by miR-146a-5p in the regulation of follicle functions in chicken. The study demonstrated that miR-146a-5p suppressed cell growth, lipids accumulation, and progesterone biosynthesis in chicken GC. Through targeting association validations, we identified delta 4-desaturase, sphingolipid 1 (DEGS1) as capable of interacting with miR-146a-5p. Co-transfection experiments further confirmed that DEGS1 reversed the impairment of GC functions by miR-146a-5p. Moreover, we discovered that miR-146a-5p suppressed AKT phosphorylation, while DEGS1 enhanced AKT phosphorylation. Phosphatidylinositol-3 kinase (PI3K) inhibitor (LY294002) studies showed that miR-146a-5p would inhibit AKT phosphorylation by governing the DEGS1/AKT pathway, which in turn regulates GC function. In summary, the findings revealed that miR-146a-5p suppressed cell growth, lipid deposition, and progesterone biosynthesis via the DEGS1/AKT pathway. These results may further enrich our understandings of how non-coding RNA regulates productive performance in chickens.