转移前龛是肿瘤转移的重要条件，主要由原发部位的肿瘤细胞通过外泌体等多种形式对靶器官微环境进行“改造”而形成。目前已有报道肿瘤干细胞来源的外泌体可以促进转移前龛的形成，microRNA作为外泌体的成分之一，在这一过程中发挥重要作用。我们前期研究发现，miR-1207-5p可以下调β-catenin蛋白水平调控肿瘤干细胞活性，影响肿瘤微环境中的血管生成和肿瘤相关巨噬细胞的功能，抑制肿瘤转移和生长，但其分子机制还未明确。本项目将从非编码RNA和蛋白质修饰方面研究miR-1207-5p对β-catenin的分子调控机制，通过动物模型、高通量测序和质谱分析研究miR-1207-5p对肿瘤干细胞转录组及其外泌体成分的影响，深入解析miR-1207-5p对转移前龛的调控作用。我们的研究成果将为肿瘤转移的防治提供新的靶点。

Pre-metastatic niche is a favorable microenvironment for subsequent metastases and invasion of cancer cells in secondary organs and tissue sites and is mainly established through a complex interaction of factors that derived from primary tumor, including exosomes. It has been reported that the cancer stem cell (CSC)-derived exosomes could promote pre-metastatic niche formation and the microRNAs in exosomes might play a key role in the regulation. Our previous studies confirmed that the miR-1207-5p could regulate the CSC behavior by inhibiting β-catenin expression and had significant effect on angiogenesis and the functions of tumor-associated macrophages in tumor microenvironment. However, the underlying mechanisms are still unclear. In this project, we propose to identify the roles of miR-1207-5p in pre-metastatic niche formation from two aspects. i) To reveal the mechanism of miR-1207-5p in regulating β-catenin expression through non-coding RNA interaction and post-translational modification. ii) To detect the effect of miR1207-5p on CSC transcriptome and the constituent of exosomes through high-throughput sequencing, mass spectrometry and animal models. Our findings would provide a potential target for prevention and treatment of cancer metastasis and invasion.