TRIM25-mediated ferroptosis resistance is closely associated with poor prognosis in hepatocellular carcinoma

Objective: TRIM25 has been reported to promote hepatocellular carcinoma (HCC) cell survival by activating the Keap1-Nrf2 pathway. However, its expression profile in clinical HCC specimens and its potential role in regulating ferroptosis remain to be elucidated. This study aimed to determine the expression pattern of TRIM25 in primary HCC and its association with clinicopathological features and prognosis, utilizing both bioinformatic analysis and experimental validation in clinical samples and cell lines. In parallel, we investigated the regulatory effect of TRIM25 on ferroptosis in HCC cells, thereby offering experimental insights that could inform prognosis assessment and the development of targeted therapies for HCC. Methods: , liver cancer cell models with TRIM25 knockdown or overexpression were established. The effects of TRIM25 modulation on cell proliferation and ferroptosis susceptibility were assessed using CCK-8 assays, colony formation assays, and ferroptosis-related biochemical markers. Results: , TRIM25 silencing suppressed liver cancer cell proliferation and increased ferroptosis-related phenotypes, as indicated by increased ferrous iron and MDA levels, reduced GSH content and SOD activity, and elevated ROS and lipid peroxidation. Conversely, TRIM25 overexpression promoted proliferation, attenuated ferroptosis-related phenotypes, and reduced oxidative stress. Conclusion: TRIM25 is highly upregulated in HCC and significantly associated with poor clinical prognosis. Functionally, TRIM25 promotes tumor cell survival by reducing the sensitivity of HCC cells to ferroptosis. These findings suggest that TRIM25 may serve as a promising prognostic indicator and a potential therapeutic target for modulating ferroptosis pathways in HCC.