长非编码RNA对成瘤性乳腺癌干细胞分化和自我更新的调控作用研究

项目名称： 长非编码RNA对成瘤性乳腺癌干细胞分化和自我更新的调控作用研究

项目编号： No.81472731

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： 于风燕

作者单位： 中山大学

项目金额： 75万元

中文摘要： 乳腺癌干细胞是乳腺癌发生、发展、转移和治疗后复发的根源。申请人前期研究发现微小RNA（miRNA）对乳腺癌干细胞自我更新、多向分化和治疗抵抗等具有调控作用。近年发现长非编码RNA（lncRNA）可与miRNA相互调控，并与干细胞的发育和肿瘤的发生等有紧密的联系。因此，本课题拟进一步探索调控乳腺癌干细胞生物学特性的lncRNA的功能及与miRNA表达的相互调控机制。首先分析乳腺癌干细胞和非癌干细胞lncRNA的表达差异，对比前期研究中乳腺癌干细胞的miRHA表达谱，寻找特异表达的目标lncRNA。探索干预lncRNA水平对乳腺干细胞自我更新能力、多向分化潜能、体内成瘤能力及化疗耐药等生物学特性的调控作用，从而观察它们对乳腺癌干细胞成瘤和转移的影响。进一步研究lncRNA与miRNA之间的互相调控关系，阐明lncRNA参与调控乳腺癌干细胞特性的分子信号通路的机制。

中文关键词： C21_乳腺肿瘤；肿瘤干细胞；非编码RNA

英文摘要： Breast cancer stem cells (BCSCs) are the source of oncogenesis, development, metastasis and recurrence of breast cancer. Our previous studies revealed that a panel of microRNAs regulated many aspects of the stem cell-like properties of breast cancer cells,such as self-renewal, multipotent differentiation,epithelial-mesenchymal transition(EMT), and chemotherapeutic resistance. Recently, long non-coding RNA (lncRNA) has been reported to mutually regualte miRNA,and closly corralated with the development of stem cell and tumor occurrence. Therefore, our research is proposed to further explore the function of lncRNAs which regulate the biological characteristics of BCSCs and mutual regulation mechanism with the expression of miRNA. We will first analysis the difference expression of lncRNA between BCSCs and non-cancer stem cells, and compare with miRNA expression spectrum in the previous study, look for specific expression of lncRNA. Then we will explore whether lncRNA regulate the self-renewal, multi-differentiation potential, oncogenesis and resistance to chemotherapy of BCSCs in vivo and in vitro, when the level of lncRNA was incresed or decreased. Further, we will study the regulatory mechanism between lncRNA and miRNA, elucidate the signaling pathways of lncRNA in participating in the regulation of the stemness of BCSCs.Investigating the machiner that govern lncRNA expression in BCSCs will not only help us to extend the knowledge of molecular basis for the stemness of BCSCs, but also guide us to develop novel approaches that may manipulate lncRNA expression for therapeutic purposes.

英文关键词： Breast cancer;cancer stem cells;non-coding RNA