利用课题组前期建立的适合肿瘤研究的lncRNA组学平台，本课题将探索lncRNA调控恶性肿瘤转移的功能，及其差异表达的机制。通过高通量技术检测食管癌与乳腺癌原发灶和转移灶配对的临床组织样本差异表达的lncRNA，同时系统识别与肿瘤转移调控蛋白相互作用的lncRNA。探索DNA甲基化、组蛋白修饰和转录因子对差异lncRNA转录的调控，以及lncRNA在细胞内转运、修饰和降解的机制，以明确候选lncRNA差异表达的原因。利用体外细胞培养和体内荷瘤鼠模型，通过干预lncRNA表达和关键候选lncRNA的转基因/基因敲除鼠模型，探索lncRNA调控肿瘤细胞可塑性、肿瘤转移和对治疗耐受的作用。最后检测候选lncRNA在肿瘤临床标本的表达和定位，分析其与肿瘤转移和患者预后的关系。本研究将识别一批具有肿瘤转移调控功能的lncRNA，解析其差异表达的机制，为肿瘤转移的早期诊断和靶向转移癌的治疗提供新思路。

We have established the research platforms to study long noncoding RNAome, lncRNA-protein interaction, tumor cell plasticity, and tumor micro-environment. We will also perform RNA immunoprecipitation-deep sequencing of metastasis-associated proteins to identify their interacting lncRNAs in paired primary and metastasis esophageal and breast cancer samples. We will then investigate the function of these lncRNAs to regulate tumor cell plasticity and metastasis both in vitro and in vivo; study the roles of lncRNA regulating the expression, modification and function of metastasis-associated proteins; and explore the underlying molecular mechanisms to understand the regulating mode by which lncRNAs act on signal transduction. We will also isolate stromal cells in clinical tumor samples to identify stromal specific lncRNAs and investigate the roles and mechanisms by which they regulate the activation and metastasis-promoting functions of stromal cells; explore the possibility of lncRNA to act as signal molecules to target tumor cell and regulate metastasis. By carrying out this project, we will be able to understand the role and mechanisms of lncRNAs in regulating tumor cell plasticity, metastasis-associated cell signaling, and tumor micro-environment, and to provide novel targets for therapies targeting tumor metastasis.