本团队前期建立了适合肿瘤研究的长非编码RNA组学方法和lncRNA与蛋白相互作用的研究体系，及肿瘤微环境和肿瘤细胞可塑性的体内外模型。在此基础上，本项目将系统研究lncRNA调控恶性肿瘤转移的作用和机制。利用食管癌和乳腺癌原发灶和转移灶的配对临床组织样本，通过系统识别筛选转移癌中差异表达的lncRNA，在体内外模型中研究lncRNA调控肿瘤细胞可塑性和肿瘤转移的功能。并探索lncRNA调控转移相关蛋白表达、修饰和功能的作用，明确其相互作用的分子机理，阐明lncRNA对转移信号传导的调节模式。在肿瘤临床标本分离间质细胞，识别间质细胞特异的lncRNA，研究其调控间质细胞激活和促转移的功能和机理，并探索其作为信号分子通过细胞外泌体穿梭微环境靶向肿瘤细胞，调控肿瘤转移的作用和机制。本研究将阐明lncRNA在肿瘤细胞可塑性、肿瘤转移信号传导和肿瘤微环境调控中的机制，并为肿瘤转移干预措施提供新靶点。

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.