Analysis Of Gene Expression Profiling And Disease Pediction In HUVEC-C Cells Exposed To Endosulfan

Endosulfan is widely used as an organochlorine pesticide which was classified into persistent organic pollutants by the Stockholm Convention in 2011.Endosulfan is widespread in environmental medium characterized by high toxicity,persistence,bioaccumulation and fluidity.Therefore,it has a long-term harm to human health which cannot be ignored.Our previous study found that endosulfan could induce vascular endothelial toxicity,resulting in cell cycle arrest,apoptosis and inflammation.Endosulfan-induced endothelial dysfunction is thought to be closely related to human diseases.To reveal the molecular mechanism in endosulfan-induced endothelial toxicity and the connection between endosulfan and human diseases,I studied the effect of endosulfan on gene expression profile in human vascular endothelial cells and predicted human diseases related to endosulfan exposure.In this study,DNA microarray was performed to analyze gene expression profile in human vascular endothelial cells exposed to 20,40 and 60 ?M endosulfan.GO and KEGG-Pathway analysis were used to confirm the connection between phenotypic changes and gene expression alteration due to endosulfan exposure.Further,NextBio and Metacore database were combined to predict the most relevant human disease,cardiovascular disease,and cancers that are associated with endosulfan exposure.Key genes in the pathogenesis of prostate cancer was also selected.Finally,I investigated the effect of endosulfan on the pregression of prostate cancer and function of key gene related to prostate cancer.The results demonstrated that endosulfan increased the number of altered genes in a dose-dependent manner.Endosulfan-induced changes in various biological processes and signal pathways were consistent with phenotypic changes of endothelial injury due to endosulfan exposure.These down-regulated genes were associated with cytoskeleton organization at the low dose(20?M),and involved in cell cycle and apoptosis at the high dose(60?M).Those up-regulated genes were linked to inflammatory response and transcriptional misregulation in cancer at the higher doses(40 and 60?M).Endosulfan may be relevant to human digestive system diseases,metabolic diseases and cancers including liver cancer,prostate cancer and leukemia.PTP4A3 is a key gene in prostate cancer associated with endosulfan Endosulfan improved the PTP4A3 mRNA expression level to promote the migration ability of prostate cancer.This study will provide a scientific basis for molecular mechanism of human diseases induced by endosulfan.