GPX8 deficiency-induced oxidative stress reprogrammed m6A epitranscriptome of oral cancer cells

• Published in: Epigenetics 2023-12, Vol.18 (1), p.2208707-2208707
• Main Authors: Chen, Xun, Yuan, Lingyu, Zhang, Lejia, Chen, Liutao, He, Yi, Wang, Chao, Wu, Jie, Chen, Shangwu, Zhao, Wei, Yu, Dongsheng
• Format: Article
• Language: English
• Subjects: A modification; A regulatory genes; Alpha-Ketoglutarate-Dependent Dioxygenase FTO - genetics; DNA Methylation; glutathione peroxidase 8 (GPX8); Humans; Hydrogen Peroxide - metabolism; m6a modification; m6a regulatory genes; Mouth Neoplasms - genetics; Oxidative Stress; Peroxidases - genetics; Peroxidases - metabolism; reactive oxygen species (ROS); Research Paper; RNA-Binding Proteins - genetics; RNA-Binding Proteins - metabolism; Transcriptome
• ISSN: 1559-2294; 1559-2308
• DOI: 10.1080/15592294.2023.2208707

Glutathione peroxidase 8 (GPX8) is a key regulator of redox homoeostasis. Whether its antioxidant activity participates in the regulation of m 6 A modification is a crucial issue, which has important application value in cancer treatment. In this study, MeRIP-seq was used to explore the characteristics of transcriptome-wide m 6 A modification in GPX8-deficient oral cancer cells. Oxidative stress caused by the lack of GPX8 resulted in 1,279 hyper- and 2,287 hypo-methylated m 6 A peaks and 2,036 differentially expressed genes in GPX8-KO cells. Twenty-eight differentially expressed genes were related to the cell response to oxidative stress, and half of them changed their m 6 A modification. In GPX8-KO cells, m 6 A regulators IGF2BP2 and IGF2BP3 were upregulated, while FTO, RBM15, VIRMA, ZC3H13, and YTHDC2 were downregulated. After H 2 O 2 treatment, the expression changes of RBM15, IGF2BP2, and IGF2BP3 were further enhanced. These data indicated that GPX8-mediated redox homoeostasis regulated m 6 A modification, thereby affecting the expression and function of downstream genes. This study highlights the possible significance of GPX8 and the corresponding m 6 A regulatory or regulated genes as novel targets for antioxidant intervention in cancer therapy. Lack of GPX8 caused oxidative stress of oral cancer cells. Oxidative stress induced by GPX8 deficiency reprogrammed m 6 A epitranscriptome. GPX8 deletion-caused oxidative stress regulated expression of m 6 A regulatory genes. m 6 A modification of antioxidant genes is the adaptive response of cells to oxidative stress.