长链非编码RNA在镉毒作用中的表达谱筛选及功能研究

项目名称： 长链非编码RNA在镉毒作用中的表达谱筛选及功能研究

项目编号： No.81202236

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 预防医学、地方病学、职业病学、放射医学

项目作者： 周志衡

作者单位： 广州医科大学

项目金额： 23万元

中文摘要： 研究显示：长链非编码RNA(lncRNA)与DNA损伤与修复、DNA甲基化及组蛋白乙酰化有关。项目申请人在前期研究发现，镉能引起DNA损伤与DNA修复基因表达下调，并引起异常甲基化和乙酰化。但其机制是否与lncRNA的调控有关？未见报道。本项目拟通过高通量的LncRNA芯片和生物信息学技术筛选出镉恶性转化人支气管上皮细胞（16HBE）中LncRNA差异表达谱，通过镉作业人群进行验证，并进一步运用LncRNA过表达技术和LncRNA沉默技术探索和验证镉毒作用中LincRNA在细胞周期，细胞凋亡、DNA损伤、DNA修复和DNA甲基化和组蛋白乙酰化中的调控功能;经过表遗传逆转,探索LncRNA和甲基化和乙酰化的互调控作用。本项目将为寻找LncRNA作为镉毒早期生物标志物的研究奠定基础，为探讨镉毒性和致癌机制研究提供新的思路，对阐明LncRNA在镉毒性中的的调控功能有积极的意义。

中文关键词： 长链非编码RNA；镉；人支气管上皮细胞；生物标记物；

英文摘要： Recent studies have shown that long noncoding RNAs (lncRNA) are known to play important regulatory roles in DNA damage, DNA damage, DNA repair genes expression , DNA methylation and histone acetylation.We previously established a model system of morphological cell transformation with Cadmium chloride (CdCl2) in human bronchial epithelial cells (16HBE) and found that Cadmium can produce genotoxic and mutagenic events, arrest cell growth ,obviously cause apoptosis and DNA damage, inhibit DNA repair gene expression and epigenetic changes. However, It is not known whether the DNA damage and repair, epigenetic changes regulated by lncRNA in Cadmium toxicity.In the current study, our arm is to identify abnormal expression profiling of lncRNA via lncRNA microarray in 16HBE cells induced by cadmium. Bioinformatic analysis of predicted target genes(gene ontology, pathway and network analysis) will be done for further research. The abnormal expression of lncRNA will be tested in human bronchial epithelial cells line induced by cadmium, rat model of chronic Cadmium exposure, and Cadmium exposed workers.The main regulation function of lncRNA to cell cycle, cell apoptosis, DNA damage, DNA repair genes expression , DNA methylation and histone acetylation will be verificated by Technology of over expression and RNA interferenc

英文关键词： LncRNAs；Cadmium；Human bronchial epithelial cells；Biomarker；