miR-183/-96/-182基因簇对乳腺癌诊断及治疗作用的机制研究

项目名称： miR-183/-96/-182基因簇对乳腺癌诊断及治疗作用的机制研究

项目编号： No.31201056

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 遗传学与生物信息学、细胞生物学

项目作者： 朱曲波

作者单位： 中南大学

项目金额： 23万元

中文摘要： 乳腺癌是乳房腺上皮细胞在多种致癌因子作用下, 生长增殖机制失常而引起的疾病。本项目将对乳腺癌中高度表达的miR-183/-96/-182基因簇进行深入研究，达到诊断及治疗乳腺癌的目的。研究内容包括：1）通过RNA印记法比较不同类型乳腺癌中miR-183/-96/-182基因簇的表达量。2）通过5'-RACE及启动子分析研究miR-183/-96/-182基因簇自身调控机理。3）通过RT-PCR,蛋白印记及荧光素酶分析确定部分miR-183/-96/-182基因簇靶向基因及其对乳腺癌的调控机理。4）操纵miR-183/-96/-182基因簇表达，改变癌细胞属性。本研究能确定miR-183/-96/-182基因簇靶向治疗的乳腺癌类型；阐明miR-183/-96/-182基因簇自身及其对靶向基因的调控机理；从而降低乳腺的肿瘤发生率，迁移速度和侵入性。

中文关键词： miR-183/-96/-182；乳腺癌；细胞增殖；转录调控；抗癌药物

英文摘要： Breast cancer is a family of diseases that involve unregulated breast epithelial cell growth and division, which is caused by many different carcinogenic factors. This project try to figure out a new strategy for breast cancer diagnosis and treatment based on the intensive studies on miR-183/-96/-182 cluster which is highly expressed in breast cancer.The specific aims of this project include: 1) Compare the expression levels of miR-183/-96/-182 cluster in different types of breast cancer by northern blot. 2)Research on the regulation mechanism of miR-183/-96/-182 cluster itself by 5'-RACE and promoter analysis. 3)Confirm partial target genes of miR-183/-96/-182 cluster and find out miR-183/-96/-182 cluster's function on breast cancer by RT-PCR, western blot and luciferase reporter assay. 4)Observe the impacts of miR-183/-96/-182 on breast cancer cells after changing its expression level. Our work can determine the specific breast cancer types that can be treated by miR-183/-96/-182 cluster targeted therapy; understand the regulation mechanism of miR-183/-96/-182 cluster itself and its function on its target genes; and finally reduce the tumorigenesis,migration and invasion of breast cancer by regulating the expression level of miR-183/-96/-182 cluster.

英文关键词： miR-183/-96/-182；breast cancer；cell proliferation；transcription regulation；anti-cancer drugs