Circulating MicroRNAs in association with urinary arsenic: A community-based multi-center study in China

The profile of plasma miRNAs in association with arsenic exposure remains largely unclear. We aim to identify plasma miRNAs assoicated with urinary arsenic using a two-stage design in Chinese population. The discovery group, Shimen panel, consists of 19 high vs. low arsenic-exposed pairs selected from 1095 residents in an arsenic-contaminated area. The validation group, Wuhan-Zhuhai panel, consists of 53 community-dwelling participants with moderate arsenic exposure. Plasma miRNAs were measured by microarray in the Shimen panel and by sequencing in the Wuhan-Zhuhai panel. Arsenic levels in urine and plasma were quantified using inductively coupled plasma mass spectrometry. During the discovery stage, 16 miRNAs were found to be differentially expressed between high and low urinary arsenic groups in the Shimen panel (fold change >2, P < 0.05). Seven miRNAs (miR-101-3p, miR-142-3p, miR-148a-3p, miR-15a-5p, miR-199a-3p, miR-27b-3p, and miR-340-5p) were validated to have a positive association with log-transformed urinary arsenic levels in the Wuhan-Zhuhai panel (P < 0.05). Furthermore, five of the seven miRNAs were also associated with arsenic in plasma. The identified miRNAs were primarily associated with cancer-related pathways. These identified miRNAs would serve as crucial biomarkers for arsenic exposure, elucidating the epigenetic mechanisms underlying arsenic-induced toxicity and carcinogenesis.