AS3MT is related to relative RNAs and base modifications of p53 in workers exposed to arsenic

Abstract

Abstract AS3MT, the key enzyme involved in the methylation of arsenic, is closely associated with DNA methylation. However, the relationship between them is not known. In this study, we recruited workers from four arsenic plants and individuals who resided in villages far away from the four plants. Arsenic compounds, relative indices, 28 relative RNAs, and base modifications of exons 5–8 of p53 were detected separately. Several methods were used to analyze the associations between them. We found that the AS3MT RNA was closely associated with lncRNAs, miRNAs, and mRNAs related to miRNA production and maturation, tumorigenesis, and base modifications of p53, they probably have causal relationships. Arsenic compounds and the relative indices of metabolic transformation might have limited roles. Base modifications of exons 7 and 8 of p53 had significant synergistic effects on the expression of the AS3MT RNA and a series of genetic indices. But miR-190, miR-548, and the base modifications of exon 5 of p53 had substantial inhibitory effects. This study showed that the AS3MT RNA could strongly affect genotoxicity and carcinogenesis, which is initiated by arsenic or AS3MT but greatly influenced by other factors. There was a close interaction among the AS3MT RNA, relative mRNAs, lncRNAs, the miRNA networks, and the base modifications of different fragments of p53.