Significance: Aberrant redox homeostasis, characterized by the enhancement of intracellular reactive oxygen species (ROS) and antioxidant defenses, is among the well-known cancer hallmarks. Understanding the regulatory mechanisms of redox homeostasis in cancer cells has become the focus of many studies. Epigenetic and post-translational modifications (PTMs), as pivotal regulators of multiple biological processes, play critical roles in tumorigenesis and development. Recent Advances: DNA and RNA methylation are important forms of epigenetic modifications. Recent evidence suggests that DNA/RNA methylation and PTMs can modulate redox homeostasis in multiple manners including affecting key molecules in ROS production, elimination, and redox-related signaling, thereby participating in tumor progression. Critical Issues: The regulatory effects of DNA/RNA methylation and PTMs on ROS are of crucial importance for tumor progression. In this review, we introduce the dual role of ROS in cancer, and then focus on the mechanistic role of DNA/RNA methylation and PTMs, especially ubiquitination and acetylation, in regulating redox homeostasis to involve in cancer progression. Future Directions: A complete understanding of how epigenetics and PTMs function in the regulation of redox homeostasis in cancer progression might expand a new direction for the progression mechanisms and therapeutic targets of cancer. Antioxid. Redox Signal. 39, 531-550.
Keywords: DNA methylation; ROS; m6A; post-translational modifications; redox homeostasis.