Identification of miRNAs induced by low-dose methylmercury exposure and their roles in inflammatory responses using human aortic endothelial cells.

BACKGROUND: Exposure to methylmercury (MeHg) is predominantly attributed to consumption of marine products. However, the general population is exposed to low MeHg levels, which can induce chronic inflammation. Although some MeHg-related microRNAs (miRNAs) have been reported, their functions remain elusive. The objective of this study was to identify the miRNAs induced by low-level MeHg exposure in a human endothelial cell line (HAECs). This study aimed to determine the specific miRNAs induced by low-level MeHg exposure using a HAECs as a potential novel and sensitive biomarker. The roles of miRNAs in inflammatory processes have been examined. METHODS: Using HAECs, a miRNA microarray assay was performed to identify miRNAs with altered expression upon exposure to a non-cytotoxic MeHg level (0.1 and 1.5 µM). The expression patterns of interleukin-6 and -8, cyclooxygenase 2 (COX-2), RelB, and prostaglandin E2 (PGE2) were examined after transfection of the identified miRNAs with mimics/inhibitors. RESULTS: Although the microarray assay identified six MeHg-specific miRNAs, miR-3613-5p, upregulated by 0.1 and 1.5 µM MeHg exposures, demonstrated the best reproducibility in HAECs. Transfection with the miR-3613-5p mimic enhanced the MeHg-induced inflammatory responses, including PGE2 and COX-2 protein levels, whereas the miR-3613-5p inhibitor suppressed these inflammatory responses. CONCLUSION: This study observed that miR-3613-5p is induced by low-dose MeHg exposure, plays a crucial role in the inflammatory process, and could serve as a novel and sensitive biomarker for low-level MeHg exposure.