转录因子NAC1通过调节FOXQ1介导上皮间质转化影响卵巢癌紫杉醇化疗耐药的作用及机制研究

项目名称： 转录因子NAC1通过调节FOXQ1介导上皮间质转化影响卵巢癌紫杉醇化疗耐药的作用及机制研究

项目编号： No.81502245

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： 高敏

作者单位： 山东大学

项目金额： 18万元

中文摘要： 化疗耐药是导致卵巢癌患者复发率高预后差的最主要原因，近年来上皮间质转化（EMT）在介导肿瘤化疗耐药中的作用受到广泛关注。我们前期研究发现转录因子NAC1高表达与卵巢癌早期复发密切相关， EMT重要调控因子FOXQ1是NAC1下游作用分子。本项目拟通过基因沉默及过表达技术，从细胞及动物实验水平全面验证NAC1-FOXQ1分子通路在卵巢癌紫杉醇化疗耐药过程中的作用；然后在分子水平阐述NAC1转录调控FOXQ1介导 EMT发生影响卵巢癌耐药的分子生物学机制；最后通过分析肿瘤组织中NAC1、FOXQ1及EMT相关分子表达，评估其独自或联合作为卵巢癌患者化疗耐药及预后分子标志物的潜在临床应用价值。该研究不仅有助于进一步揭示卵巢癌耐药的分子作用机理，而且有望为卵巢癌分子标志物及靶向治疗研究提供新的理论依据，对改善卵巢癌患者预后将起到积极作用，具有重要的临床应用价值。

中文关键词： 卵巢肿瘤；紫杉醇；化疗耐药；上皮间质转化；NAC1

英文摘要： Chemoresistance is one of the most important reasons that responsible for the high recurrence and poor prognosis of ovarian cancer. Recently, Epithelial-Mesenchymal Transition (EMT) has been concerned a lot because of its important function in regulating chemoresistance. Previously, we found transcription factor NAC1 was related to early recurrence of ovarian cancer; FOXQ1, which was well known of regulating EMT, was found to be one of NAC1’s downstream effectors. In this study, firstly, we will analysis the function of NAC1-FOXQ1 pathway in mediating paclitaxel resistance in ovarian cancer by using RNAi and gene overexpression methods in vivo and ex vivo; further more, we will explore the potential molecular mechanism of how NAC1 transcriptionally regulating FOXQ1 contributes to chemoresistance through EMT; finally, we will evaluate the possibility of NAC1、FOXQ1 and EMT relating factors acting as ovarian cancer prognosis markers. Thus, this project would be useful for further clarify the exact mechanisms of neoplasm chemoresistance and may provide new clues on ovarian cancer prevention and therapy. It should have important clinical values in improving patients prognosis.

英文关键词： ovarian cancer;paclitaxel;chemoresistance;epithelial mesenchymal transition;NAC1