Analysis of miRNA and mRNA expression in the dysregulation of insulin secretion in MIN6 cells exposed to microcystin-leucine-arginine

Abstract

Microcystin -leucine-arginine (MC-LR), produced by freshwater cyanobacteria, is a potential pancreatic β-cell toxin. In this study, the function of the mouse pancreatic β-cell line, MIN6, was evaluated after MC-LR exposure, and the underlying molecular mechanisms were explored. Exposure to MC-LR for 24 h was found to inhibit cell viability and impair insulin secretion. Such findings indicate that β-cell function would be impaired following MC-LR treatment. The microarray results revealed altered miRNA and mRNA expression profiles that might be responsible for the abnormal function of MIN6 cells. Further, miRNA-gene network analysis demonstrated that miR-29b-3p, miR-6967-5p, miR-3473, miR-7061-5p, Xkr4, Tmem178b, Scp2, Ypel2, and Kcnj11 are key miRNAs and genes in the MC-LR-induced MIN6-cell toxicity. The altered expression levels of several miRNAs (e.g., miR-320-5p, miR-770-5p, miR-99a-3p, and miR-375-5p) and genes (e.g., Pklr and Gpd2) involved in insulin secretion or the onset of diabetes were also identified in MIN6 cells after treatment with MC-LR. Collectively, these findings provide evidence of the toxic effects of MC-LR on β-cells and the underlying molecular mechanisms of its glycometabolism toxicity. MCs may thus possibly play an important role in the development of diabetes mellitus in humans.

Keywords: Insulin secretion; Microarray; Microcystin-LR; Pancreatic β-cells; miRNA and mRNA expression.