miR-363-5p regulates liver disease via the MAPK/ERK signaling pathway by targeting CPEB2 in chicken.

The liver is vital for laying hens, metabolizing nutrients, detoxifying, producing bile for digestion, regulating energy, and synthesizing yolk precursors, directly impacting egg production and health. MicroRNAs (MiRNAs) serve as central hepatic regulators, particularly influencing egg-laying efficiency through metabolic pathway control, detoxification modulation, and vitellogenesis. While miR-363-5p is implicated in liver metabolism and development across species, its specific roles in avian hepatic function remain underexplored. This study demonstrated that miR-363-5p induces lipogenesis, oxidative stress, and inflammation in chicken hepatocytes. Additionally, this study defined the interaction mechanism between miR-363-5p and its target genes and verified the cytoplasmic-polyadenylation element binding protein 2 (CPEB2) as a target gene of miR-363-5p using dual-luciferase assays. It was also confirmed that the effect of CPEB2 knockdown on hepatocytes was the same as that of miR-363-5p overexpression, including enhanced lipogenesis, elevated oxidative stress, and pronounced inflammatory responses. Furthermore, we confirmed that the miR-363-5p/CPEB2 axis modulates the MAPK/ERK signaling pathway, contributing to hepatic steatosis in chickens. Our findings establish a novel miR-363-5p/CPEB2/MAPK regulatory axis in avian lipid metabolism, providing new insights into the pathogenesis of fatty liver disease in poultry.