Suo Yuhong, Wang Yu, Su Yu, Wang Qianyi, Jia Jidong, Zhao Xinyan
Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China.
State Key Laboratory of Digestive Health, Beijing, China.
J Transl Autoimmun. 2025 Aug 6;11:100303. doi: 10.1016/j.jtauto.2025.100303. eCollection 2025 Dec.
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.
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.
自身免疫性肝炎（AIH）是一种相对罕见的肝脏疾病病因，若不进行干预，预后较差。铁死亡是一种经典的细胞死亡形式，在多种疾病中起关键作用，但其在AIH中的作用仍不清楚。因此，我们研究了铁死亡在AIH中的作用及其机制。
在此，我们使用在线公共数据库和工具进行了广泛的生物信息学分析，包括基因本体论、京都基因与基因组百科全书以及基因集富集分析。使用铁死亡相关检测试剂盒、定量实时聚合酶链反应和蛋白质免疫印迹分析，通过临床组织和细胞样本验证结果。
我们在对照组和AIH组之间获得了449个差异表达的微小RNA（DEmiRNAs）。其中，通过评估hsa-miR-122-5p和hsa-miR-143-3p的诊断价值、表达水平和靶基因数量，筛选出它们作为潜在的关键微小RNA。富集分析显示hsa-miR-122-5p与铁死亡相关途径之间存在显著关联。体外实验证实，hsa-miR-122-5p抑制SLC7A11的表达，从而促进AIH中的铁死亡。
总之，我们的研究表明，hsa-miR-122-5p作为一个潜在的治疗靶点，通过抑制SLC7A11的表达促进铁死亡，这为AIH的发病机制提供了新的见解，并为创新治疗策略铺平了道路。
