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

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.

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.

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.

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.