hnRNP K/E对HPV16整合的调控及其在宫颈癌变进展中的作用

项目名称： hnRNP K/E对HPV16整合的调控及其在宫颈癌变进展中的作用

项目编号： No.81473060

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： 王金桃

作者单位： 山西医科大学

项目金额： 75万元

中文摘要： HPV16与宿主细胞整合是宫颈细胞癌变的主要原因，但其机制不明。鉴于hnRNP K、E在基因转录和转录后调控中具有独特作用，且可与HPV 16不同ORF区域RNA发生特异性结合，提示，hnRNP K、E势必可通过调控HPV16基因的表达在宫颈病变的进展中发挥作用。为了验证这一假设，本研究以HPV16整合相关的关键基因E2、L1、L2 与hnRNP K、E的相互作用为切入点，从人群研究和体外实验两个层面，探讨hnRNP K、E与HPV16整合基因及宫颈病变的关系，观察hnRNP K、E与HPV16 整合基因在细胞内的定位和共定位，分析它们之间的相互作用与结合能力，同时应用siRNA干扰技术对以上生物学功能加以验证。以此综合评价hnRNP K、E对HPV16整合基因的调控及其在宫颈癌变进展中产生的效应，为深入宫颈癌的病因和发病机制研究提供新的理论依据，为探寻宫颈癌变的防治靶点开拓思路。

中文关键词： 宫颈癌变；核不均一核糖核蛋白；人乳头瘤病毒；调控机制

英文摘要： It is well known that the integration of human papillomavirus 16 (HPV 16) into the host genome is the crucial cause in the progression of cervical cancerization, but the mechanism is not precisely clear. Based on that hnRNP K/E have unique regulatory function in gene transcription and post-transcription, and can bind HPV16 gene RNA in Open Reading Frame (ORF). We hypothesize that hnRNP K/E may involve in the development of cervical cancer through regulating the HPV 16 expression. In order to confirm this hypothesis, our study will focus on the interaction between hnRNP K/E and the key integrative genes E2, L1, L2 of HPV16. We will first explore the relationship between hnRNP K/E and HPV16 integrative genes expression, as well as the association between hnRNP K/E and cervical cancer in vivo and in vitro. Then we will observe the immunofluorescent co-localization of hnRNP K/E and HPV16 genes in cervix cells and analyze their integration effects. Furthermore, to confirm such effects, we will combine vitro experiments by siRNA technology. According to these results, this study aims to evaluate the effects and possible molecular biology mechanisms of hnRNP K/E through regulating HPV16 integrative genes expression in the progression of cervical carcinomas. So may provide evidences for etiology and pathogenesis of cervical cancer and afford novel insights into the cancer management.

英文关键词： cervical canceration;hnRNP;HPV16;regulatory mechanism