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

ABSTRACT: Glutathione peroxidase 8 (GPX8) is a key regulator of redox homeostasis. Whether its antioxidant activity participates in the regulation of m6A modification is a crucial issue, which has important application value in cancer treatment. MeRIP-seq was used to explore the characteristics of transcriptome-wide m6A modification in GPX8-deficient oral cancer cells in this study. Oxidative stress caused by lack of GPX8 resulted in 1,279 hyper- and 2,287 hypo-methylated m6A 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 m6A modification. In GPX8-KO cells, m6A regulators IGF2BP2 and IGF2BP3 were upregulated, while FTO, RBM15, VIRMA, ZC3H13 and YTHDC2 were downregulated. After H2O2 treatment, the expression changes of RBM15, IGF2BP2 and IGF2BP3 were further enhanced. These data indicated that GPX8-mediated redox homeostasis regulated m6A modification, thereby affecting the expression and function of downstream genes. This study highlights the possible significance of GPX8 and the corresponding m6A regulatory or regulated genes as novel targets for antioxidant intervention in cancer therapy

ORGANISM(S): Homo sapiens

PROVIDER: GSE224718 | GEO | 2023/08/10

REPOSITORIES: GEO

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2021-10-26 | GSE165863 | GEO

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Project description:As the most common post-transcriptional RNA modification, m6A methylation extensively regulates the structure and function of RNA. The dynamic and reversible modification of m6A is coordinated by m6A writers and erasers. m6A reader proteins recognize m6A modification on RNA, mediating different downstream biological functions. mRNA m6A modification and its corresponding regulators play an important role in cancers, but its characteristics in the precancerous stage are still unclear. In this study, we used oral precancerous DOK cells as a model to explore the characteristics of transcriptome-wide m6A modification and major m6A regulator expression in the precancerous stage compared with normal oral epithelial cell HOEC and oral cancer cell SCC-9 through MeRIP-seq and RT-PCR. Compared with HOEC cells, we found 1180 hyper-methylated and 1606 hypo-methylated m6A peaks and 354 differentially expressed mRNAs with differential m6A peaks in DOK cells. Although the change of m6A modification in DOK cells was less than that in SCC-9 cells, mRNAs with differential m6A in both cell lines were enriched into many identical GO terms and KEGG pathways. Among the 20 known m6A regulatory genes, FTO, ALKBH5, METTL3 and VIRMA were slightly upregulated or downregulated in DOK cells, but the expression of 10 genes such as METTL14/16, FTO and IGF2BP2/3 changed significantly in SCC-9 cells. Our data suggest that precancerous cells showed, to some extent, changes of m6A modification. Identifying some key m6A targets and corresponding regulators in precancerous stage may provide potential intervention targets for the prevention of cancer development through epigenetic modification in the future.

2022-09-21 | GSE213714 | GEO

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