Regulation of Ferroptosis by MicroRNAs

Abstract

Ferroptosis is a form of iron-dependent cell death characterized by the accumulation of lipid reactive oxygen species (ROS). Increasing evidence suggests that ferroptosis is associated with reduction of glutathione (GSH) and inactivation of glutathione peroxidase 4 (GPX4). In addition, peroxidation of polyunsaturated fatty acids (PUFAs) is believed to be another reason for the initiation and execution of ferroptosis. Although first identified in cancer cells, ferroptosis has been significantly implicated in the neurodegenerative diseases (i.e., Alzheimer’s, Parkinson’s, and Huntington’s diseases), stroke, traumatic brain injury, acute renal failure, drug-induced hepatotoxicity, hepatic and heart ischemia/reperfusion injury and T-cell immunity. MicroRNAs (miRNAs) are 20–23-nucleotide small RNA molecules that control gene expression by reducing the translation and stability of mRNAs in many cellular processes. Recent studies have shown that miRNAs-mediated posttranscriptional regulation of gene expression represents an integral part of the ferroptosis regulatory network and may have a substantial effect on ferroptosis-related physiological and pathological conditions. This chapter summarizes the current knowledge of miRNA regulation of ferroptosis and attempts to integrate this novel regulatory layer into the known ferroptosis pathways. Since miRNAs are important biomarkers and several miRNA-targeted therapeutics have reached clinical development, a better understanding of the interaction between miRNAs and ferroptosis may ultimately benefit the diagnosis and treatment of many severe diseases in the future.