Gga-miR-146b-3p promotes apoptosis and attenuate autophagy by targeting AKT1 in chicken granulosa cells

Theriogenology. 2022 Sep 15:190:52-64. doi: 10.1016/j.theriogenology.2022.07.019. Epub 2022 Aug 3.

Abstract

The normal development of follicles determines the reproductive performance of females. Granulosa cells (GC) play crucial roles in follicular maturation. Numerous studies have shown that miRNAs are involved in the regulation of GC. According to our previous sequencing data, gga-miR-146b-3p was differentially expressed in normal and atretic chicken follicles. In this study, we verified that gga-miR-146b-3p attenuated proliferation and autophagy but promoted apoptosis in chicken GC. Threonine kinase1 (AKT1), a key member of the phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway, was predicted to be a target gene of gga-miR-146b-3p via bioinformatic analysis. Dual-luciferase reporter gene assays were used to determine target relationships. Moreover, knockout of AKT1 decelerated proliferation and autophagy while accelerating the apoptosis of GC. However, overexpression of AKT1 reversed these results. In summary, our results demonstrated that gga-miR-146b-3p repressed the proliferation and autophagy of chicken GC while up-regulating apoptosis by targeting AKT1 through the PI3K/AKT signaling pathway. These findings may provide great insights for further exploration of the molecular regulation of gga-miR-146b-3p and AKT1 on the functions of GC during folliculogenesis.

Keywords: Apoptosis; Autophagy; Gga-miR-146b-3p; Granulosa cells; PI3K/AKT; Proliferation.

MeSH terms

  • Animals
  • Apoptosis / genetics
  • Autophagy / genetics
  • Cell Proliferation / genetics
  • Chickens* / genetics
  • Chickens* / metabolism
  • Female
  • Granulosa Cells / metabolism
  • MicroRNAs* / metabolism
  • Phosphatidylinositol 3-Kinases / genetics
  • Phosphatidylinositol 3-Kinases / metabolism
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / metabolism

Substances

  • MicroRNAs
  • Proto-Oncogene Proteins c-akt