Effects of Subtoxic Concentrations of Atrazine, Cypermethrin, and Vinclozolin on microRNA-Mediated PI3K/Akt/mTOR Signaling in SH-SY5Y Cells

Abstract

Endocrine-disrupting chemicals (EDCs) are different natural and synthetic chemicals that may interfere with several mechanisms of the endocrine system producing adverse developmental, metabolic, reproductive, and neurological effects in both human beings and wildlife. Among pesticides, numerous chemicals have been identified as EDCs. MicroRNAs (miRNAs) can regulate gene expression, making fine adjustments in mRNA abundance and regulating proteostasis. We hypothesized that exposure to low doses of atrazine, cypermethrin, and vinclozolin may lead to effects on miRNA expression in SH-SY5Y cells. In particular, the exposure of SH-SY5Y cells to subtoxic concentrations of vinclozolin is able to downregulate miR-29b-3p expression leading to the increase in the related gene expression of ADAM12 and CDK6, which may promote a pro-oncogenic response through the activation of the PI3K/Akt/mTOR pathway and counteracting p53 activity. A better understanding of the molecular mechanisms of EDCs could provide important insight into their role in human disease.

A Silent Threat: Exploring the Impact of Endocrine Disruption on Human Health

“…EDCs have been shown to affect the neuronal system in both animals and humans. Using novel bioinformatics analyses, Dr. Hrelia and her team published a study in this Special Issue [ 6 ] and revealed that exposure of a neuroblastoma cell line, SH-SY5Y, to subtoxic concentrations of vinclozolin (VNZ) dysregulated microRNA (miR-29-3p) expression as well as perturbed the expression of its downstream ADAM12 and CDK6, which may, in turn, activate the PI3K/Akt/mTOR signaling pathway and suppress tumor suppressor p53 level. This observation was specific to VNZ as the authors compared the effects with two other EDCs, atrazine and cypermethrin, which are commonly used in the agriculture industry.…”