MiR-122-5p modulates ferroptosis via SLC7A11: A potential therapeutic target in autoimmune hepatitis

Background & aims: Autoimmune hepatitis (AIH) is a relatively rare cause of liver disease with a poor prognosis without intervention. Ferroptosis, a classical form of cell death, plays a crucial role in various diseases, but its role in AIH remains unclear. Therefore, we investigated the role of ferroptosis in AIH and its mechanism. Methods: Here, we performed extensive bioinformatic analyses using online public database and tools, including Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and Gene Set Enrichment Analysis. Ferroptosis-related assay kits, quantitative real-time polymerase chain reaction, and Western blot analysis were used to validate the results by using clinical tissues and cell samples. Results: We obtained 449 differentially expressed microRNAs (DEmiRNAs) between the control and AIH groups. Among these, hsa-miR-122-5p and hsa-miR-143-3p were screened out as potential key miRNAs by evaluating their diagnostic value, expression levels, and number of target genes. Enrichment analysis revealed a significant association between hsa-miR-122-5p and ferroptosis-related pathways. It was confirmed by in vitro assays that hsa-miR-122-5p inhibited the SLC7A11 expression, thereby promoting ferroptosis in AIH. Conclusions: To summarize, our study demonstrated that hsa-miR-122-5p, as a potential therapeutic target, promotes ferroptosis by inhibiting the expression of SLC7A11, which provides new insights into the pathogenesis of AIH and paves the way for innovative treatment strategies.