项目名称： 利用诱导多能性干细胞技术建立鼻咽癌致病模型

项目编号： No.81502353

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 陈琪

作者单位： 中山大学

项目金额： 18万元

中文摘要： 鼻咽癌是高发于我国南方的恶性肿瘤，与Epstein-Barr virus（EBV）密切相关。由于不是每个EBV携带者都会患鼻咽癌，EBV感染后鼻咽上皮细胞癌变过程的研究极为困难。.诱导多能性干细胞是通过向体细胞中转入某些转录因子从而得到的与胚胎干细胞类似的具有多能性的细胞。这些细胞可以分化为多种体细胞，且具有其来源细胞的基因组特征并保留有一定程度的表观遗传记忆。据此可知，来源于正常上皮细胞与不同鼻咽癌细胞的诱导多能性干细胞在分化过程中对EBV的易感性与稳定性不尽相同，其重新癌变的倾向性也不同。.本项目拟建立不同来源的诱导多能性干细胞在分化为上皮细胞过程中被EBV感染后重新癌变的模型，研究细胞基因组和表观遗传学特性在鼻咽癌致病中的作用。同时利用该模型可以追踪鼻咽癌相关基因在细胞癌变过程中的作用并探讨其相关机制，为鼻咽癌致病机理的研究提供新的思路，对鼻咽癌的预防有重要意义。

中文关键词： 鼻咽癌；诱导多能性干细胞；EB病毒

英文摘要： The Epestein-Barr Virus (EBV)-associated nasopharyngeal carcinoma (NPC) is prevalent in South China. Not every EBV-carrieers got NPC, making the tracing of carcinogenesis of EBV-infected nasopharyngeal epithelial cells extremely difficult..The induced pluripotent stem cells are pluripotent cells derived from somatic cells by transcription factor-based reprogramming, with much similarities with embryonic stem cells. They can not only differentiate to many types of somatic cells but also maintain the same genetic background and certain epigenetic memories of the original cells, so that they may appear different in susceptibility to EBV infection, stability in EBV latency and canceration tendency..This project will first model the canceration process of the EBV-infected epithelial cells, which are derived from the induced pluripotent stem cells of normal nasopharyngeal epithelial cells or different NPCs. Then, the relationships between genetic and epigenetic background with nasopharyngeal carcinogenesis will be discussed. With our carcinogenesis model, the canceration process caused by seleted NPC-related genes can be traced and elucidated. This model will provide new tools for research on the mechanism of nasopharyngeal carcinogenesis, and is of important value in the prevention of NPC development.

英文关键词： nasopharyngeal carcinoma;induced pluripotent stem cell;epstein-barr virus