中文摘要
化学致癌因素是人类恶性肿瘤高发的主要病因,有效地识别和评价环境有害化学物的致突变、致癌性,对肿瘤的防治起着重要的作用。基于长链非编码RNA(LncRNA)在生物体重要生命活动中发挥着极广泛的调控作用,与人类肿瘤密切相关,其异常表达存在于多种肿瘤发生、发展过程中。本研究项目将在深化提出的“通道假说”和前期研究工作基础上,筛选致突变/可疑致癌物甲基丙烯酸环氧丙酯(GMA)致16HBE细胞由正常演变为恶性细胞过程不同阶段差异LncRNA;通过分析在多个时间点上以同/异模式变化LncRNA,确定GMA诱导细胞恶变特异LncRNA,绘制相关基因表达调控网络图;结合前期差异表达基因和甲基化基因等研究结果,以及构建的生物信息学分析模型,预测锁定LncRNA功能,研究其对靶基因的调控作用,探讨GMA致细胞恶变的演变过程中特异LncRNA功能及其作用,寻找可用于环境有害化学物暴露监测的分子标志物。
英文摘要
Chemical carcinogen is the main causes of human malignant tumors. The capability of recognition and assess the mutagenicity and oncogenicity of chemicals would play an important role in prevention and control of cancer. Long non-coding RNA (LncRNA) exerts comprehensive regulatory effect throughout the biological activities and is closely associated with human cancer. The abnormal expression of LncRNA can be detected at initiation and development stage in many human cancers. This research, based on the channel hypothesis and previous study, is to screen the difference of related LncRNA in the development of malignant transformation of 16HBE (human bronchial epithelial) cells induced by Glycidyl methacrylate (GMA), a mutagenic and suspected carcinogenic chemical. The specific LncRNA will be confirmed through gradual comparison in different stage followed by network diagrams about regulation of related gene expression. Combined with the previous research about differential expression gene and DNA methylation gene, the established bio-information analysis model is to predict and verify the function of LncRNA as well as the regulation effect on target gene. The outcomes about the function and mechanism of the specific LncRNA in the cell malignant transformation induced by GMA can be helpful in searching for molecular marker used in exposure monitor of environmental hazardous chemicals.
