miR-4719/miR-6082调控BRIT1信号网络介导乳腺癌化疗耐受的研究

项目名称： miR-4719/miR-6082调控BRIT1信号网络介导乳腺癌化疗耐受的研究

项目编号： No.81472487

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： 张波

作者单位： 华中科技大学

项目金额： 72万元

中文摘要： 化疗耐受严重影响乳腺癌化疗疗效，阐明化疗抵抗机制至关重要。微小RNA（microRNA）和BRIT1及DNA损伤修复作为肿瘤研究靶点备受关注，但尚未见两者相互作用调控化疗抵抗的报道。本课题组既往研究证实了BRIT1能调控p53，且与DNA损伤修复密切相关。进一步的研究显示，BRIT1是调控乳腺癌化疗耐药的关键分子，且与miR-4719/miR-6082相关。为进一步探索miR-4719/miR-6082靶向BRIT1介导乳腺癌化疗抵抗的分子机制，本项目拟在乳腺癌细胞中，通过干预miR-4719/miR- 6082靶向BRIT1，获得其调节乳腺癌化疗敏感性的直接实验依据，揭示miR-4719/miR-6082通过靶向BRIT1信号通路导致乳腺癌化疗耐受的分子机制，阐明miR-4719/miR- 6082调控BRIT1信号在乳腺癌化疗耐受中的作用和临床意义，为逆转肿瘤耐药提供新思路和新靶点。

中文关键词： C21_乳腺肿瘤；BRIT1；微小RNA；化疗耐受

英文摘要： Chemoresistance severely affects the efficacy of chemotherapy in breast cancer, thus, it's essential to clarify the mechanism of chemoresistance. Increasing attention are focused on microRNA and BRIT1 due to their widely targets. Our previous studies demonstrated that BRIT1 regulates p53 and plays a role in the DNA damage and repair pathway, which results in the chemoresistance in breast cancer, which was associated with miR-4719/miR-6082. In order to clarify the molecular mechanisms of miR-4719/miR-6082 targeting BRIT1 and regulating the chemoresistance of breast cancer, based on our breast cancer models in vitro and in vivo, we plan to get the directly evidence that of miR-4719/miR-6082 mediates the chemoresistance by targeting BRIT1. Then we would like to clarify the mechanism of miR-4719/miR-6082 in regulating BRIT1 signal pathway and contributing to the chemoresistance of breast cancer. Finally, we will demonstrate the clinical significance of miR-4719/miR-6082 and BRIT1 signal pathway in chemoresistance of breast cancer. Our project will provided a novel insight of chemoresistance and novel targets in reversing the chemoresistance of breast cancer.

英文关键词： breast cancer;BRIT1;MicroRNA;chemoresistance