毛蕊异黄酮通过干预LncRNA-WDR7-7-Rab27B信号通路抑制乳腺癌细胞迁移侵袭作用的研究

项目名称： 毛蕊异黄酮通过干预LncRNA-WDR7-7-Rab27B信号通路抑制乳腺癌细胞迁移侵袭作用的研究

项目编号： No.81460403

项目类型： 地区科学基金项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 田晶

作者单位： 桂林医学院

项目金额： 50万元

中文摘要： 长链非编码RNA(LncRNA)表达水平异常与肿瘤发生发展密切相关。本项目以癌细胞侵袭特性为切入点，以毛蕊异黄酮处理ER(+)乳腺癌细胞，筛选表达显著下调的LncRNA-WDR7-7及其靶基因Rab27B为研究对象。Rab27B可通过影响外泌体分泌，调节下游信号MAPK、AKT，促进肿瘤侵袭转移。结合本课题组前期实验基础，毛蕊异黄酮抑制乳腺癌细胞生长作用机制包括下游Ras-p38 MAPK、PI3K/Akt信号通路的调节，我们推测毛蕊异黄酮通过干预LncRNA-WDR7-7-Rab27B通路及其下游MAPK、AKT信号分子，抑制乳腺癌迁移侵袭。本项目拟通过细胞生物学、分子生物学和动物实验，检测LncRNA-WDR7-7、Rab27B在体内外的信号级联，探讨毛蕊异黄酮抗乳腺癌转移的信号转导通路及作用靶点，从而为乳腺癌治疗提供新的药物与靶点选择。

中文关键词： C21_乳腺肿瘤；毛蕊异黄酮；植物雌激素；长链非编码RNA；侵袭

英文摘要： Long non-coding RNAs (LncRNA), mRNA-like transcripts longer than 200nt, is involved in tumor invasion and metastasis via activation of downstream signaling pathways. Given our focus on metastasis of breast cancer, we here cover insights into the function of LncRNA-WDR7-7 that was downregulated by high concentration calycosin in ER-positive cells, as well as its target gene Rab27B. The mechanism of action of Rab27B is believed to be induction of exosome secretion and subsequent regulation of MAPK, AKT pathways, leading to migration and invasion of tumor cells. Moreover, our preliminary study suggested that selective regulation of Ras-p38 MAPK and PI3K/Akt signaling pathway is correlated with calycosin-mediated inhibitory effects in ER-positive breast cells. Therefore, we hypothesize that the LncRNA-WDR7-7-Rab27B pathwey, followed by regulation of MAPK and AKT signaling, may be responsible for calycosin-induced inhibition of metastasis. By transwell assays, scratch method, Western blot, qPCR, xenograft tumor growth and immunohistochemistry, our project will investigte the relationship among calycosin, LncRNA-WDR7-7 and Rab27B in breast cancer. The results will not only help to further ascertain calycosin-mediated signaling pathway, but also provide experimental foundation for calycosin's future clinical applications for ER-positive breast cancer.

英文关键词： breast cancer;calycosin;phytoestrogen;long non-coding RNA;metastasis