Low-level arsenic species exposure and plasma lncRNA signature in healthy Chinese adults: A profile and functional analysis

Chronic exposure to arsenic (As) is known to disrupt epigenetic regulation. However, the relationship of arsenic species and methylation capacity with circulating long non-coding RNAs (lncRNAs) remains poorly understood. We investigated the associations of urinary arsenic species and arsenic methylation capacity with 1362 plasma lncRNAs in 160 Chinese adults from the community-dwelling population. Arsenate [As(V)] was inversely associated with five lncRNAs, while the primary methylation index (PMI) was positively related t o eight lncRNAs (FDR < 0.15). Tissue specificity analysis using the Genotype-Tissue Expression (GTEx) database revealed enriched expression of these lncRNAs in As-targeted organs, such as skin and kidney. Notably, plasma levels of lncRNA AATBC were associated with the expression in leukocytes of itself and adjacent genes (P < 0.05), suggesting that leukocytes may be its source or target. The identified lncRNAs were primarily involved in oxidative stress, inflammation, and carcinogenesis pathways. Significant association between the identified lncRNAs and lipid damage biomarker 8-iso-prostaglandin F2α (8-isoPGF 2α ) was further confirmed our findings. Overall, these results identified novel genome-wide changes in lncRNAs within plasma and leukocytes, offering new mechanistic insights into the epigenetic regulation underlying the health hazards of chronic low-level arsenic exposure. • Exposure to arsenic species was associated with altered plasma levels of lncRNAs. • Arsenic species-related lncRNAs showed tissue-specific expression. • These lncRNAs were enriched in oxidative stress, inflammation, and carcinogenesis. • As-related lncRNA AATBC participated in lipid damage, plausibly linked to 8-isoPGF 2α .