Copper (Cu) is widely used in animal husbandry [1], serving as a growth promoter [2], resisting bacteria [3], and enhancing immunity [4]. However, excessive intake of Cu can result in Cu deposition in organisms, which leads to toxic effects on the liver, kidney, digestive tract, and other organs [[5], [6], [7]]. Our earlier research established that the broilers’ liver tissue was obviously damaged after being fed with a high dose of Cu for a long time. Further study discovered that the mitochondrial structure and function of broiler liver tissue were damaged, and the cells apoptosis [8].

MicroRNAs (miRNAs), known as small endogenous RNAs, interact with the 3′UTR of the target mRNA to adversely affect the translation activity of many proteins [9]. miRNAs play a guiding hand in regulating various biological and metabolic processes, involving cell growth [10], proliferation [11], differentiation [12], and cell death [13]. Meanwhile, the mounting evidence also confirmed that autophagy can be regulated and modulated by miRNAs [14]. Autophagy is a conserved cellular self-degradation process for damaged or aged cellular constituent reutilization. During pathological process, autophagy might be a preservation strategy for cells. For instance, miR-100-5p enhanced autophagy levels, which helped to alleviate osteoarthritis and maintain cartilage homeostasis [15]. However, autophagy activation is regarded as a double-edged sword, leading to cellular damage. Overexpression of miR-215-5p triggered autophagy through targeting PI3K, which was the reason of myocardial injury [16]. Our previous investigation has found that Cu overload contributes to mitochondrial dysfunction and mitophagy, which is regulated by miR-1285 in pig jejunal epithelial cells [17]. However, the regulation mechanism of miRNA on the autophagy induced by Cu exposure in the chicken hepatocytes remains uncertain. Based on high-throughput miRNA sequencing of liver tissue, miR-455-3p was noticed to be repressed under a Cu exposure situation, which motivated us to further explore its potential regulatory mechanism.

To the extent of our knowledge, the molecular mechanism of miR-455-3p regulation of Cu-induced hepatocytes in chickens remains unclear. Therefore, we aimed to elucidate that miR-455-3p might be a potential regulator of autophagy in hepatocytes. Our research obtained novel information regarding the mechanism of Cu (II) toxicity and provides a basis for further revealing the mechanism of chronic Cu poisoning.