miR-31调控乳腺干细胞的功能研究

项目名称： miR-31调控乳腺干细胞的功能研究

项目编号： No.31271584

项目类型： 面上项目

立项/批准年度： 2013

项目学科： 生物科学

项目作者： 于政权

作者单位： 中国农业大学

项目金额： 80万元

中文摘要： 乳腺干细胞精确地调控自我更新和分化两种行为，用于维持乳腺组织自身各种细胞的均衡。这种干细胞调控机制的失控往往与癌症发生密切相关。在研究乳腺干细胞的基因表达谱时，我们发现了一个在乳腺干细胞特异表达而且在乳腺癌中高表达的microRNA，miR-31。 在前期工作中，我们建立了miR-31过表达的转基因小鼠。我们发现miR-31过表达可以通过激活Wnt信号通路活性来促进小鼠乳腺干细胞的自我更新，而抑制细胞分化。这表明miR-31很可能在乳腺干细胞的调控起到关键作用。在此基础上，本项目采用基因敲除，转基因小鼠模型和乳腺癌小鼠模型，结合乳腺细胞系和乳腺癌细胞系，全方位深入探讨miR-31在乳腺干细胞和乳腺癌中的功能。该课题将为乳腺癌的诊断和治疗提供更为充分的科学依据，为药物设计提供新的靶点，具有重要的科学意义和应用价值。

中文关键词： microRNA；乳腺干细胞；乳腺癌；Wnt；NFkB

英文摘要： Mammary gland homeostasis is maintained by multipotent mammary stem cell (maSC) precisely regulating its self-renewal and differentiation. The abnormality of the regulational mechanism is highly associated with tumorigenesis. Among our microRNA profilings of mammary gland stem cell, miR-3 is specifically expressed mammary gland stem cell, and highly expressed in human breast cancer as well. To study miR-31 function, we established inducible miR-31 transgenic mice. We found that overexpression of miR-31 can promote mammary stem cell self-renewal, but inhibit cell differentiation by activating Wnt signaling pathway. It suggested that miR-31 is a key regulator on mammary gland behavior. In this proposal, we will deeply study the role of miR-31 in mammary gland stem cell and breast cancer using miR-31 conditional knockout mouse, miR-31 transgenic mouse, MMTV-Her2 mouse, mammary cell line, and breast cancer cell line systems. This research is highly significant to provide scientific evidences for the diagnosis and therapy of breast cancer, and to develop new targets for drug designation as well.

英文关键词： microRNA；乳腺干细胞；乳腺癌；Wnt；NFkB