硫丹暴露HUVEC-C细胞的基因表达谱和疾病预测分析

发布时间：2018-03-24 06:13

本文选题：硫丹　切入点：HUVEC-C细胞　出处：《大连海事大学》2017年硕士论文

【摘要】：硫丹是一种应用广泛的有机氯农药,在2011年被斯德哥尔摩公约列为持久性有机污染物,在环境介质中广泛存在,具有高毒性、持久性、生物富集性、可长距离传输的特点,因此,其对人类健康的远期危害不能被忽视。前期研究发现硫丹具有血管内皮细胞毒性,能够引起血管内皮细胞周期阻滞、凋亡和炎症反应,导致血管内皮细胞功能失调,考虑可能与人类疾病关系密切。为了揭示硫丹暴露引起血管内皮细胞功能失调的分子机制及与人类疾病的关系,本课题探讨了硫丹对血管内皮细胞基因表达谱的影响并进行了人类疾病预测分析。本研究采用DNA microarray分析了硫丹暴露(20,40,60μM)对HUVEC-C细胞的基因表达谱的影响,利用GO分析和KEGG Pathway探讨了硫丹暴露引起的HUVEC-C细胞表型变化与基因表达变化间的关联,进一步联合NextBio和Metacore数据库预测了与硫丹暴露最相关的人类疾病、心血管疾病和癌症;筛选了促进前列腺癌发展的关键基因,最后验证了硫丹促进前列腺癌发展的作用及其关键基因的功能。结果表明,硫丹能够引起差异表达的基因数量增加,具有剂量依赖性关系。硫丹引起多种生物学过程和信号通路发生变化与硫丹引起血管内皮细胞损伤的表型变化一致。低剂量硫丹(20μM)暴露引起下调的基因主要涉及细胞骨架调节,较高剂量(40μM和60μM)硫丹暴露引起下调的基因涉及细胞周期和凋亡而上调的基因涉及炎症反应和癌的转录失调信号通路。硫丹暴露与人类的消化系统疾病、代谢疾病、心血管疾病和癌症相关。其中最相关的癌症是肝癌、前列腺癌和白血病。硫丹促进前列腺癌发展的关键基因是PTP4A3,可能通过提高PTP4A3的mRNA表达水平而促进前列腺癌的迁移能力。这项研究将为揭示硫丹暴露引起人类疾病的分子机制提供新的依据。
[Abstract]:Endosulfan, a widely used organochlorine pesticide, was listed as a persistent organic pollutant by the Stockholm Convention in 2011. It is widely present in environmental media and has the characteristics of high toxicity, persistence, bioconcentration and long distance transport. Therefore, its long-term harm to human health can not be ignored. Previous studies have found that endosulfan has vascular endothelial cell toxicity, can cause vascular endothelial cell cycle arrest, apoptosis and inflammation, leading to vascular endothelial cell dysfunction, In order to reveal the molecular mechanism of vascular endothelial cell dysfunction caused by endosulfan exposure and its relationship with human disease, In this study, the effect of endosulfan on gene expression profile of vascular endothelial cells (VECs) and the prediction of human disease were studied. DNA microarray was used to analyze the effect of endosulfan exposure on the gene expression profile of HUVEC-C cells. Go analysis and KEGG Pathway were used to explore the relationship between phenotypic changes and gene expression changes in HUVEC-C cells induced by endosulfan exposure. Furthermore, combined with NextBio and Metacore databases, the most relevant human diseases, cardiovascular diseases and cancer were predicted. The key genes for the development of prostate cancer were screened, and the role of endosulfan in promoting the development of prostate cancer and the function of the key genes were verified. The results showed that endosulfan could cause an increase in the number of differentially expressed genes, The changes in many biological processes and signal pathways induced by endosulfan are consistent with the phenotypic changes in vascular endothelial cell injury induced by endosulfan. The down-regulated genes induced by exposure to low-dose endosulfan 20 渭 M mainly involve cytoskeletal regulation. Exposure to endosulfan at a higher dose of 40 渭 M and 60 渭 M involves down-regulated genes related to cell cycle and apoptosis, while up-regulated genes involve inflammatory responses and transcriptional dysfunctional signaling pathways of cancer. Endosulfan exposure is associated with diseases of the human digestive system, metabolic diseases, Cardiovascular disease is associated with cancer. The most relevant cancer is liver cancer. Prostate cancer and leukemia. The key gene that endosulfan promotes the development of prostate cancer is PTP4A3, which may promote the migration of prostate cancer by increasing the level of mRNA expression of PTP4A3. This study will be used to reveal that endosulfan exposure causes human disease. To provide a new basis for the molecular mechanism.
【学位授予单位】：大连海事大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R114

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