m6A demethylation of cytidine deaminase APOBEC3B mRNA orchestrates arsenic-induced mutagenesis

Abstract

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Epigenetic Dysregulations in Arsenic-Induced Carcinogenesis

“…They confirmed that A3B was a downstream target of FTO in lung tissues from As-exposed mice. FTO protein expression was positively correlated with A3B protein expression in tumor samples from human NSCLC patients [ 222 ]. Another study also confirmed that As treatment increased FTO expression, decreased m6A RNA methylation, and consequently induced malignant transformation and tumorigenesis in keratinocytes.…”

The Epitranscriptomic Mechanism of Metal Toxicity and Carcinogenesis

“…The important role of FTO up-regulation in arsenic mutagenesis has also been reported in another study. Gao et al found that short-term arsenic (2 µM) treatment in lung cancer cells up-regulated the expression of APOBEC3B (A3B), an endogenous inducer of somatic mutations leading to chromosomal instability [ 61 ]. It was determined that up-regulation of A3B is required for arsenic-induced DNA damage and mutagenesis [ 61 ].…”

“…Gao et al found that short-term arsenic (2 µM) treatment in lung cancer cells up-regulated the expression of APOBEC3B (A3B), an endogenous inducer of somatic mutations leading to chromosomal instability [ 61 ]. It was determined that up-regulation of A3B is required for arsenic-induced DNA damage and mutagenesis [ 61 ]. Mechanistic studies showed that arsenic treatment decreased the level of m6A modification near the stop codon of A3B mRNA, which increased the stability of A3B mRNA [ 61 ].…”

Transcriptome-wide m6A methylome analysis uncovered the changes of m6A modification in oral pre-malignant cells compared with normal oral epithelial cells

“…A single m 6 A regulator can exert biological function via different target genes in the same cancer ( 26 , 27 ). As described above, the same m 6 A regulator may act different functions in different tumors ( 6 – 10 ). These findings demonstrated that regulatory networks of m 6 A methylation in cancers are extremely complex and need to be further explored.…”

“…The role of m 6 A modification involves many aspects of tumors. For example, demethylase FTO-mediated m 6 A demethylation of cytidine deaminase APOBEC3B mRNA promotes arsenic-induced mutagenesis ( 6 ). FTO promotes growth and metastasis of gastric cancer through m 6 A demethylation of caveolin-1 and metabolic regulation of mitochondrial dynamics ( 7 ).…”