miR-21及miR-214双向调节乳腺癌细胞骨转移的分子机制研究

项目名称： miR-21及miR-214双向调节乳腺癌细胞骨转移的分子机制研究

项目编号： No.81201820

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 肿瘤学1

项目作者： 晁腾飞

作者单位： 华中科技大学

项目金额： 27万元

中文摘要： 骨转移是晚期乳腺癌的常见并发症，严重影响患者生活质量。已有研究表明miRNAs与乳腺癌密切相关，但miRNAs在乳腺癌骨转移中的作用尚不明确。申请者在前期预实验中发现，与乳腺癌原发灶相比，骨转移组织中miR-21(升高)与miR-214(下降)表达量存在显著性差异。生物信息学分析及预实验揭示miR-21/miR-214的靶基因参与了多条骨转移信号通路，两者的调节作用相反。本研究以乳腺癌细胞及小鼠作为研究体系，结合生物信息学和分子生物学实验，预测并验证miR-21/miR-214的靶基因，调查它们对骨转移通路下游信号分子表达的影响，明确miR-21/miR-214双向调节乳腺癌骨转移的分子机制；另外计划通过miRNA芯片筛查并研究其它可能参与乳腺癌骨转移的miRNAs，完善miRNAs参与乳腺癌骨转移的分子机制，为晚期乳腺癌骨转移患者提供新的治疗靶点。

中文关键词： 乳腺癌；骨转移；微小RNA；环形RNA；

英文摘要： Bone metastasis is a common complication of advanced breast cancer and has a serious impact on the quality of patients' life. It has been suggested that a variety of miRNAs involved in breast cancer development and growth, but the mechanism of miRNAs in breast cancer bone metastases is not clear. In the preliminary experiment, we found there is significant differences in expression levels of miR-214 (decreased) and miR-21(increased) in bone metastases tissues and breast cancer tissues. Bioinformatics analysis and our preliminary experiments have suggested target genes of miR-21/miR-214 involved in multiple bone metastases signaling pathways, which implied they played opposite regulation on the bone metastasis. This study will adopt breast cancer cell lines and mice as research systems, combined with bioinformatics and molecular biology experiments to predict and verify miR-21/miR-214 target genes, and investigate their impact on the expression of downstream signaling molecules in the pathways. In addition, miRNA microarray will be applied to investigate other miRNAs that may be involved in breast cancer bone metastases. The aim of the study is to clarify the molecular mechanisms of bi-directional regulation miR-21 and miR-214 on breast cancer bone metastasis and to provide new therapeutic targets for advanced br

英文关键词： breast cancer；bone metastasis；miRNAs；circRNAs；