gga-miR-449b-5p Regulates Steroid Hormone Synthesis in Laying Hen Ovarian Granulosa Cells by Targeting the IGF2BP3 Gene

Abstract

MiRNAs have been found to be involved in the regulation of ovarian function as important post-transcriptional regulators, including regulators of follicular development, steroidogenesis, cell atresia, and even the development of ovarian cancer. In this study, we evaluated the regulatory role of gga-miR-449b-5p in follicular growth and steroid synthesis in ovarian granulosa cells (GCs) of laying hens through qRT‒PCR, ELISAs, western blotting and dual-luciferase reporter assays, which have been described in our previous study. We demonstrated that gga-miR-449b-5p was widely expressed in granulosa and theca layers of the different-sized follicles, especially in the granulosa layer. The gga-miR-449b-5p had no significant effect on the proliferation of GCs, but could significantly regulate the expression of key steroidogenesis-related genes (StAR and CYP19A1) (p < 0.01) and the secretion of P4 and E2 (p < 0.01 and p < 0.05). Further research showed that gga-miR-449b-5p could target IGF2BP3 and downregulate the mRNA and protein expression of IGF2BP3 (p < 0.05). Therefore, this study suggests that gga-miR-449b-5p is a potent regulator of the synthesis of steroid hormones in GCs by targeting the expression of IGF2BP3 and may contribute to a better understanding of the role of functional miRNAs in laying hen ovarian development.

β-Catenin regulates ovarian granulosa cell cycle and proliferation in laying hens by interacting with TCF4

“…Like in most animals, the egg production of laying hens is mainly controlled by the hypothalamic-pituitary-ovarian axis ( HPG ) ( Du et al, 2020 a). Following the elucidation of the endocrine mechanism of HPG, granulosa cells have been the focus of many studies on the mechanism of follicle growth and survival ( Wu et al, 2022 ). In vivo and in vitro experiments have shown that factors secreted by granulosa cells, including gonadal steroids, growth factors, and cytokines, are essential for granulosa cell survival and eventual follicle growth.…”

IGF2BP3 promotes the progression of colorectal cancer and mediates cetuximab resistance by stabilizing EGFR mRNA in an m6A-dependent manner

“…Recent research has identified rigosertib as a potent small molecule that can suppress tumorigenesis by downregulating IGF2BP3 [ 41 ]. Non-coding RNAs such as miR-486 [ 42 ] and gga-miR-449b-5p [ 43 ] are also attractive alternative approaches to target IGF2BP3. More detailed preclinical studies are required before these drugs can be considered a concrete possibility.…”

MFN2 regulates progesterone biosynthesis and proliferation of granulosa cells during follicle selection in hens

“…In hens, after synthesized in granulosa cells of the hierarchical follicle, P4 converts to E2 in theca cells catalysed by aromatase enzymes (Jing et al, 2018). E2 and P4 have been proved to be involved in the regulation of chicken ovarian function, as important regulators of follicle development and maturation, cell proliferation and differentiation (Du et al, 2020; Li et al, 2022; Wu et al, 2022). In this study, P4 biosynthesis in granulosa cells increased significantly during the follicle selection (SYF to F5), and it was incremental during the preovulatory hierarchical development.…”