Deletion of miR-122-5p Exacerbated Hyperthyroidism-Induced Liver Injury by Regulating Ferroptosis.

The aim of this study was to evaluate the effect and mechanism of miR-122-5p on hepatic injury induced by hyperthyroidism. Male Sprague Dawley rats were divided into three groups: a normal thyroid function group (sham), a levothyroxine (LT4)-induced hyperthyroidism group (T4 sodium), and a hyperthyroidism group treated with a miR-122-5p inhibitor (T4 sodium + antagomir-122-5p). Liver tissue pathology, ferroptosis and inflammatory markers, and miR-122-5p expression were assessed. Finally, rat hepatocytes (BRL-3A) were treated with carbon tetrachloride (CCL4) to explore the role of the miR-122-5p/CCDC6 axis in hepatocyte injury. We found that miR-122-5p was expressed at low levels in liver tissues from hyperthyroid rats. Inhibition of miR-122-5p aggravated liver tissue injury. Additionally, in hyperthyroid rats, inflammatory factors, iron content, and markers of ferroptosis were upregulated by miR-122-5p inhibitors. Mechanistically, miR-122-5p was found to bind to CCDC6 and negatively regulate CCDC6 expression. Furthermore, miR-122-5p deletion induced hepatocyte injury by exacerbating the ferroptosis process and mitochondrial damage in CCL4-treated hepatocytes, a process dependent on CCDC6 expression. The miR-122-5p/CCDC6 axis plays a protective role in hyperthyroidism-induced liver injury and serves as a potential target for the clinical treatment of hyperthyroidism-associated liver disease.