硫丹诱导miR-22表达变化与人内皮细胞损伤和功能失调的关联

项目名称： 硫丹诱导miR-22表达变化与人内皮细胞损伤和功能失调的关联

项目编号： No.21207012

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 环境化学

项目作者： 徐丹

作者单位： 大连海事大学

项目金额： 25万元

中文摘要： 硫丹是一类具有持久性、高毒性和生物富集特征的持久性有机污染物，由于其潜在的致癌致突变和内分泌干扰素作用，与人类许多疾病的发生有关。目前对于硫丹致病的分子机制研究仍多限于蛋白编码基因, 而非蛋白编码基因miRNA基因是否参与和如何调控硫丹导致基因表达失调，是一个急需认识的关键科学问题。miR-22是一种在转录后水平调控蛋白表达的小分子RNA，参与增殖，老化及凋亡等多种细胞学过程。我们前期的研究发现硫丹引起人脐静脉内皮细胞毒性、细胞周期阻滞、老化和凋亡，并特异性诱导了miR-22表达上调。因此本课题将在明确不同剂量的硫丹对miR-22表达变化的规律的基础上，进一步揭示miR-22对内皮细胞生物学功能的影响及对内皮细胞中特异性靶基因的调控作用，阐述miR-22变化与硫丹所诱导的内皮细胞损伤的关联，从miRNAs水平揭示硫丹引起人内皮细胞功能失调的分子机制，为硫丹致病的诊断和预防提供生物标志物。

中文关键词： 硫丹；miR-22；细胞毒性；内皮功能失调；生物标志物

英文摘要： Endosulfan is a class of persistent organic pollutants characterized by persistence, toxicity and bioaccumulation in organisms. Endosulfan has been implicated increasingly in a variety of human diseases due to its potential carcinogenicity, mutagenicity and endocrine disruptor effects. Recent studies about the molecular mechanism of human diseases induced by endosulfan are mostly limited on protein-coding genes, but it is still unknown whether and how non-coding miRNA genes are involved in epigenetic control of gene expression when exposure to endosulfan. Therefore, it becomes a key scientific problem that urgently needs to be recognized. It is known that miR-22 is a small non-coding RNA, functions in regulating protein expression at post-transcription level. It plays a critical role in many cellular processes such as cell growth, apoptosis and cellular senescence. Our preliminary study found that endosulfan induced cytotoxicity, cell cycle arrest, senescence and apoptosis in human umbilical vein endothelial cells. Interestingly, miR-22 was specifically upregulated by endosulfan. In this project, we will clarify the dose-effect of endosulfan on miR-22 expression. Based on it, we will observe the characteristic effect of miR-22 on biological functions in human endothelial cells. Further, we will analyze complica

英文关键词： endosulfan；miR-22；cytotoxicity；endothelial dysfunction；biomarker