长链非编码RNA-BMOR调控乳腺癌脑转移作用与机制研究

乳腺癌是女性最高发的癌症类型，约有15-30%乳腺癌会发生脑转移。脑转移病人呈现极差预后，现有治疗手段无法有效延长大多数脑转移病人生存期。长链非编码RNA（LncRNA）被认为是癌症临床诊疗应用的优秀候选靶标，然而LncRNA在乳腺癌脑转移中的作用及其机制还缺乏深入研究。我们课题组通过研究比较特异脑转移乳腺癌细胞系和其祖细胞之间的转录组差异表达LncRNA，挖掘并鉴定得到一个功能未知LncRNA，命名为BMOR，已通过小鼠乳腺癌脑转移模型证实BMOR促进乳腺癌脑转移的作用，并已筛选得到HNRNPK与FUS等BMOR互作蛋白和包括ADD3与SPARC等BMOR靶基因。本项目将进一步应用转录组、基因组、蛋白质组等组学手段结合生物信息学分析和生化分子实验验证，以及体内外脑转移实验和临床样本数据分析，揭示BMOR调控乳腺癌脑转移的作用与机理，探讨乳腺癌脑转移的病理机制，有重要的科学价值和临床意义。

Breast cancer is a major cancer type in women. 15–30 % of patients with metastatic breast cancer will develop brain metastases during the course of the disease Current therapies are largely palliative and fail to improve survival for the majority of patients. Many lncRNAs exhibit cell- and/or tissue/tumor-specific expression, making them excellent candidates for therapeutic applications. However, the role and mechanism of lncRNAs in brain metastasis of breast cancer are largely unknown. We identified an unknown function lncRNA, designated as Brain Metastasis-associated Oncogenic long non-coding RNA (BMOR) via investigating the differentially expressed lncRNAs between the transcriptomes of brain metastasis breast cancer cells and their parental cells. We have characterized BMOR is a real lncRNA, and proved oncogenic role of BMOR in promoting brain metastasis. To investigate how BMOR promotes brain metastasis, we have identified several BMOR interacting proteins, including HNRNPK and FUS, and BMOR targeting genes, including ADD3 and SPARC. In current proposal, we will further explore the mechanism of BMOR in promoting brain metastasis of breast cancer. We intend to uncover the function of BMOR in brain metastasis of breast cancer to improve the understanding of molecular mechanism in brain metastasis.