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

• Published in: International journal of molecular sciences Vol. 23; no. 23; p. 14538
• Main Authors: Graziosi, Agnese, Sita, Giulia, Corrieri, Camilla, Angelini, Sabrina, d'Emmanuele di Villa Bianca, Roberta, Mitidieri, Emma, Sorrentino, Raffaella, Hrelia, Patrizia, Morroni, Fabiana
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 22.11.2022; MDPI
• Subjects: 1-Phosphatidylinositol 3-kinase; AKT protein; Atrazine; Atrazine - toxicity; Cell Line, Tumor; Cypermethrin; Endocrine disruptors; Endocrine Disruptors - toxicity; Endocrine system; endocrine-disrupting chemicals; Epigenetics; Gene expression; Herbicides; Hormones; Humans; microRNA; MicroRNAs - genetics; MicroRNAs - metabolism; miRNA; Molecular modelling; Neuroblastoma - genetics; neurotoxicity; Oxazoles - toxicity; p53 Protein; Pesticides; Phosphatidylinositol 3-Kinases - metabolism; Proto-Oncogene Proteins c-akt - metabolism; Pyrethrins - toxicity; TOR protein; TOR Serine-Threonine Kinases - genetics; Vinclozolin; Wildlife; microRNA; cypermethrin; neurotoxicity; atrazine; vinclozolin; endocrine-disrupting chemicals
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms232314538

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.