Cross‐Talk between Oxidative Stress and m⁶A RNA Methylation in Cancer

Abstract

Oxidative stress is a state of imbalance between oxidation and antioxidation. Excessive ROS levels are an important factor in tumor development. Damage stimulation and excessive activation of oncogenes cause elevated ROS production in cancer, accompanied by an increase in the antioxidant capacity to retain redox homeostasis in tumor cells at an increased level. Although moderate concentrations of ROS produced in cancer cells contribute to maintaining cell survival and cancer progression, massive ROS accumulation can exert toxicity, leading to cancer cell death. RNA modification is a posttranscriptional control mechanism that regulates gene expression and RNA metabolism, and m6A RNA methylation is the most common type of RNA modification in eukaryotes. m6A modifications can modulate cellular ROS levels through different mechanisms. It is worth noting that ROS signaling also plays a regulatory role in m6A modifications. In this review, we concluded the effects of m6A modification and oxidative stress on tumor biological functions. In particular, we discuss the interplay between oxidative stress and m6A modifications.

Melatonin: Regulation of Viral Phase Separation and Epitranscriptomics in Post-Acute Sequelae of COVID-19

“…Cancer cells with aberrant oxidative and antioxidant systems often exhibit dynamic crosstalks between oxidative stress and m 6 A modifications where intracellular ROS levels can change the levels of m 6 A methylation but may also be regulated by m 6 A modifications [866]. An analysis of RNA-seq assays for mouse neuroblastoma (Neuro-2A) cells treated with paraquat (PQ)-an oxidative stress-inducing herbicide-revealed that both oxidative stress as well as antioxidative stress can generate distinct transcriptome distributions of m 6 A peaks that modified circular RNAs (circRNAs) in treated cells, where PQ-treated cells presented abundant m 6 A peaks across the CDS region but exhibited less peaks in the 3′-UTR region; whereas cells pretreated with the antioxidant N-acetylcysteine (NAC) demonstrated the exact opposite effect.…”

Potential Impact of N6-Methyladenosine RNA Methylation on Vision Function and the Pathological Processes of Ocular Diseases: New Discoveries and Future Perspectives

“…The involvement of m6A modification in redox homeostasis is evidenced by the following findings. The level of m6A methylation is increased globally in response to oxidative stress [170,171]. Hypoxic preconditioning treatment-induced protection of myoblast heart cells (H9c2) from H 2 O 2 is associated with a significant increase in the total level of m6A methylation and METTL3 expression [170]; however, inhibition of m6A methylation attenuates the protection [170].…”

“…Hypoxic preconditioning treatment-induced protection of myoblast heart cells (H9c2) from H 2 O 2 is associated with a significant increase in the total level of m6A methylation and METTL3 expression [170]; however, inhibition of m6A methylation attenuates the protection [170]. Additional studies have shown that kidney injury and dysfunction induced by excess ROS production are regulated by m6A RNA methylation [171,172].…”

“…Therefore, oxidative stress and cell death are induced in HEK293T renal cells owing to decreased PGC-1α expression. In addition, FTO has been demonstrated to inhibit apoptosis induced by oxidative stress by regulating the expression of BAX and Bcl-2 [175], suggesting that m6A methylation is closely associated with oxidative stress [171].…”

“…Chen et al [270] mapped m6A modification in four cell types with different degrees of pluripotency and found that reprogramming of mouse embryonic fibroblasts to pluripotent stem cells was boosted under increased m6A levels, whereas it was hindered under reduced m6A levels. Metabolic reprogramming in hepatocellular carcinoma cells was also mediated by m6A modification [171], suggesting that m6A modification regulation may restore normal cell functions under various pathological conditions.…”