ACSF2-mediated ferroptosis is involved in ulcerative colitis

Abstract

Aims: To investigate the role of ferroptosis-related genes in the induction into ulcerative colitis (UC) and provide new strategies for the prevention and treatment of UC.

Materials and methods: We screened the UC dataset from the GEO database and obtained ferroptosis-related genes from FerrDB and GeneCards. The R package "CancerSubtypes" was performed to identify the UC subtypes, followed by Short Time-series Expression Miner (STEM) analysis. The key genes were further screened by machine learning algorithms (LASSO and SVM-RFE). WB and IHC verified the changes in the expression content of ACSF2 in vivo and in vitro models. The changes in intracellular ROS and Fe^{2 +} levels were detected.

Key findings: Through bioinformatics analysis, we selected the ferroptosis-related gene ACSF2 (acyl CoA synthetase family member 2), which is significantly associated with immune-related pathways "Toll-like receptor signaling pathway", "NF-kappa B signaling pathway" and "NOD-like receptor signaling pathway". The expression of ACSF2 was significantly down-regulated in UC animals, Salmonella typhimurium colitis models and cell models, while the ferroptosis inhibitor Fer-1 reversed the expression of ACSF2 in LPS-induced cell models, indicating that the ferroptosis-related gene ACSF2 plays an important role in mediating ferroptosis and inflammation, and is expected to become a new target for further research.

Significance: Ferroptosis is closely associated with the development of UC, and the ferroptosis-related gene ACSF2 can be used as a potential biomarker for the diagnosis and treatment of UC.

Keywords: ACSF2; Ferroptosis; Machine learning; Ulcerative colitis.