Plasma microRNA expression profiles associated with zinc exposure and type 2 diabetes mellitus: Exploring potential role of miR-144-3p in zinc-induced insulin resistance
Zi Ye, Man Cheng, Lieyang Fan, Jixuan Ma, Yingdie Zhang, Pei Gu, Y. G. Xie, Xiaojie You, Min Zhou, Bin Wang, Weihong Chen
Abstract
Zinc exposure has been linked with disordered glucose metabolism and type 2 diabetes mellitus (T2DM) development. However, the underlying mechanism remains unclear. We conducted population-based studies and in vitro experiments to explore potential role of microRNAs (miRNAs) in zinc-related hyperglycemia and T2DM. In the discovery stage, we identified plasma miRNAs expression profile for zinc exposure based on 87 community residents from the Wuhan-Zhuhai cohort through next-generation sequencing. MiRNAs profiling for T2DM was also performed among 9 pairs newly diagnosed T2DM-healthy controls. In the validating stage, plasma miRNA related to both of zinc exposure and T2DM among the discovery population was measured by qRT-PCR in 161 general individuals derived from the same cohort. Furthermore, zinc treated HepG2 cells with mimic or inhibitor were used to verify the regulating role of miR-144-3p. Based on the discovery and validating populations, we observed that miR-144-3p was positively associated with urinary zinc, hyperglycemia, and risk of T2DM. In vitro experiments confirmed that zinc-induced increase in miR-144-3p expression suppressed the target gene Nrf2 and downstream antioxidant enzymes, and aggravated insulin resistance. Our findings provided a novel clue for mechanism underlying zinc-induced glucose dysmetabolism and T2DM development, emphasizing the important role of miR-144-3p dysregulation.