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Effects of Subtoxic Concentrations of Atrazine,Cypermethrin, and Vinclozolin on microRNA-Mediated PI3K/Akt/mTOR Signaling in SH-SY5Y Cells
Authors:Agnese Graziosi,Giulia Sita,Camilla Corrieri,Sabrina Angelini,Roberta d’  Emmanuele di Villa Bianca,Emma Mitidieri,Raffaella Sorrentino,Patrizia Hrelia,Fabiana Morroni
Affiliation:1.Department of Pharmacy and BioTechnology—FaBiT, Alma Mater Studiorum—University of Bologna, via Irnerio 48, 40126 Bologna, Italy;2.Department of Pharmacy, School of Medicine and Surgery, University of Study of Naples—Federico II, via Montesano 49, 80131 Naples, Italy;3.Department of Molecular Medicine and Medical Biotechnology, School of Medicine and Surgery, University of Study of Naples—Federico II, via Pansini 5, 80131 Naples, Italy
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.
Keywords:atrazine   cypermethrin   vinclozolin   endocrine-disrupting chemicals   neurotoxicity   microRNA
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