Cross-Regulation Between Redox and Epigenetic Systems in Tumorigenesis: Molecular Mechanisms and Clinical Applications

Significance: Redox and epigenetics are two important regulatory processes of cell physiological functions. The cross-regulation between these processes has critical effects on the occurrence and development of various types of tumors. Recent Advances: The core factor that influences redox balance is reactive oxygen species (ROS) generation. The ROS functions as a double-edged sword in tumors: Low levels of ROS promote tumors, whereas excessive ROS induces various forms of tumor cell death, including apoptosis and ferroptosis as well as necroptosis and pyroptosis. Many studies have shown that the redox balance is influenced by epigenetic mechanisms such as DNA methylation, histone modification, chromatin remodeling, non-coding RNAs (microRNA, long non-coding RNA, and circular RNA), and RNA N6-methyladenosine modification. Several oxidizing or reducing substances also affect the epigenetic state. Critical Issues: In this review, we summarize research on the cross-regulation between redox and epigenetics in cancer and discuss the relevant molecular mechanisms. We also discuss the current research on the clinical applications. Future Directions: Future research can use high-throughput methods to analyze the molecular mechanisms of the cross-regulation between redox and epigenetics using both in vitro and in vivo models in more detail, elucidate regulatory mechanisms, and provide guidance for clinical treatment. Antioxid. Redox Signal. 39, 445-471.