Bta-miR-380-3p regulates cell proliferation and adipogenesis in bovine intramuscular fat preadipocytes via targeting sterol O-acyltransferase 1.

Abstract

Intramuscular fat (IMF) deposition significantly impacts beef quality, yet microRNA (miRNA)-mediated mechanisms regulating bovine intramuscular preadipocyte development are not fully understood. This study aimed to elucidate the role of bta-miR-380-3p in preadipocyte proliferation, apoptosis, and adipogenic differentiation, identifying sterol O-acyltransferase 1 (SOAT1) as its functional target. Bta-miR-380-3p exhibited dynamic expression during adipogenesis and was highly expressed in adult bovine IMF. Gain- and loss-of-function assays showed that bta-miR-380-3p promoted DNA synthesis, cell viability, and cell-cycle progression, and reduced apoptosis-related signaling. Consistently, western blot analysis confirmed increased PCNA and CDK1 and reduced P21 after bta-miR-380-3p overexpression, whereas inhibition produced the opposite pattern. Bta-miR-380-3p also enhanced lipid droplet accumulation and upregulated adipogenic markers, with western blotting confirming increased PPARγ, FABP4, and SREBP1 protein abundance. Bioinformatics prediction, expression validation, and dual-luciferase reporter assays demonstrated that bta-miR-380-3p directly targets the SOAT1 3'UTR and negatively regulates SOAT1 expression. Functional manipulation of SOAT1 further revealed its involvement in triglyceride accumulation, adipogenic marker regulation, and proliferation-associated remodeling. Collectively, these findings reveal a bta-miR-380-3p-SOAT1 regulatory axis linking post-transcriptional control with cholesterol metabolism, preadipocyte expansion, and IMF deposition. These results provide mechanistic insight and a potential molecular target for improving marbling and meat quality traits in cattle breeding programs.