HPV E6原癌蛋白下调长链非编码RNA TUG1促进宫颈癌细胞增殖和迁移机制研究

项目名称： HPV E6原癌蛋白下调长链非编码RNA TUG1促进宫颈癌细胞增殖和迁移机制研究

项目编号： No.81472431

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 余敏敏

作者单位： 东南大学

项目金额： 70万元

中文摘要： 宫颈癌的主要致病因素为高致病基因型HPV局部持续感染，HPV DNA将以E6为主的基因片段整合到宿主细胞的DNA中，其基因产物E6原癌蛋白使细胞抑癌基因P53失活。P53能促进LncRNA TUG1的转录，TUG1可绑定PRC2调控相关基因表达。课题组前期在组织水平、细胞水平研究结果显示：宫颈癌细胞中TUG1表达下调，干扰TUG1后细胞的增殖和迁移能力增强，干扰PRC2复合物关键因子EZH2后HOXB7基因表达上调。因此提出假设：HPV E6原癌蛋白使P53失活可下调TUG1表达，TUG1可绑定PRC2进一步下调HOXB7基因，最终促进宫颈癌细胞增殖和迁移。本课题将通过大样本组织标本验证并在细胞和活体动物水平利用RIP、CHIP等技术阐述上述假设。本研究将进一步丰富宫颈癌的发病机制，为宫颈癌的早期诊断和干预提供理论依据。

中文关键词： 宫颈癌；长链非编码RNA；硫磺酸上调基因1；E6原癌蛋白；同源异型盒B7

英文摘要： The local persistent infection of human high risk HPV is a major factor that contributes to cervical cancer development.Moreover,HPV E6 DNA will be integrated into the host cell's DNA,and its' protein product would inactivate P53.P53 could promote LncRNA TUG1 transcription,and TUG1 may regulate target genes expression by binding PRC2.In our previous study,we found that TUG1 was downregulated in cervical cancer tissues compared with normal tissues,and knockdown of TUG1 expression could promote cells proliferation and invasion.Furthermore,knockdown of EZH2 expression could increase HOXB7 protein level.Therefore,we make a hypothesis that inactivation of P53 caused by HPV E6 oncoprotein leads to decreased TUG1 expression, which contributes to cervical cancer cells proliferation and invasion by regulating HOXB7 expression via binding PRC2. We will documented this mechanism by using RIP and CHIP et al methods,and our work will further our understanding about the molecular mechanisms of cervical cancer development and provide theoretical basis for early diagnosis and intervention of cervical cancer.

英文关键词： cervical cancer;long noncoding RNA(LncRNA);taurine upregulated gene 1(TUG1);E6 oncoprotein;homeobox B7(HOXB7)