Targeting epigenetic and posttranslational modifications regulating ferroptosis for the treatment of diseases

作者：Yumin Wang, Jing Hu, Shuang Wu, Joshua S. Fleishman, Yulin Li, Yin-Shi Xu, Wailong Zou, Jinhua Wang, Yukuan Feng, Jichao Chen, Hongquan Wang · 发表于：Signal Transduction and Targeted Therapy · 年份：2023 · DOI：10.1038/s41392-023-01720-0 · 被引用次数：207 · 研究领域：Epigenetics and DNA Methylation、Ferroptosis and cancer prognosis、RNA modifications and cancer

Ferroptosis, a unique modality of cell death with mechanistic and morphological differences from other cell death modes, plays a pivotal role in regulating tumorigenesis and offers a new opportunity for modulating anticancer drug resistance. Aberrant epigenetic modifications and posttranslational modifications (PTMs) promote anticancer drug resistance, cancer progression, and metastasis. Accumulating studies indicate that epigenetic modifications can transcriptionally and translationally determine cancer cell vulnerability to ferroptosis and that ferroptosis functions as a driver in nervous system diseases (NSDs), cardiovascular diseases (CVDs), liver diseases, lung diseases, and kidney diseases. In this review, we first summarize the core molecular mechanisms of ferroptosis. Then, the roles of epigenetic processes, including histone PTMs, DNA methylation, and noncoding RNA regulation and PTMs, such as phosphorylation, ubiquitination, SUMOylation, acetylation, methylation, and ADP-ribosylation, are concisely discussed. The roles of epigenetic modifications and PTMs in ferroptosis regulation in the genesis of diseases, including cancers, NSD, CVDs, liver diseases, lung diseases, and kidney diseases, as well as the application of epigenetic and PTM modulators in the therapy of these diseases, are then discussed in detail. Elucidating the mechanisms of ferroptosis regulation mediated by epigenetic modifications and PTMs in cancer and other diseases will facilitate the developmen...