Urinary total arsenic, arsenic species, and arsenic methylation capacity: an integrative profiling analysis of microRNAs in plasma and leukocytes.

Arsenic exposure remains a leading environmental health concern. MicroRNA (miRNA) dysregulation may provide a mechanistic link to arsenic-related diseases, yet the associations of arsenic species and arsenic methylation capacity with miRNA profiles in plasma and leukocytes remain largely unexplored. In a community-based population of 160 Chinese adults, we characterized the miRNA signatures of urinary arsenic species [arsenate, As(V); arsenite, As(III); monomethylarsonate, MMA; dimethylarsinate, DMA], their summed concentration (ƩAs), and arsenic methylation capacity. We further explored their potential origins, target genes, and functional pathways using RNA-seq data and public databases. After adjusting for multiple comparisons (FDR < 0.15), we identified 80 plasma miRNAs and 9 leukocyte miRNAs associated with As(V), 2 leukocyte miRNAs associated with inorganic arsenic [iAs = As(V) + As(III)], 6 plasma miRNAs associated with MMA, and 2 plasma miRNAs associated with secondary methylation index (SMI = DMA/MMA). Notably, 65 % (52/80) of the As(V)-related plasma miRNAs were located in chromosome 14q32. Most of these identified plasma miRNAs showed high enrichment in lymphocytes and arsenic-target organs, such as adrenal gland and brain. In miRNA-mRNA co-expression analysis, the identified miRNAs primarily targeted NRBF2, NUP50, OSBPL11, and SIRPD, and may be involved in pathways related to cancer, inflammation and immune function, and oxidative stress. Our findings provided novel insights into the miRNA regulatory mechanisms involved in arsenic exposure response at low to moderate levels.