Twist-1在肿瘤血管生成及上皮间充质转变中都发挥着重要的作用，从而也影响着肿瘤的发生和发展，但其作用的分子机制有待深入研究阐明。前期共筛选出11个Twist-1可能直接调控的miRNAs，确定2个血管生成拟态(VM)相关和5个上皮间充质转变（EMT）相关。本项目拟通过细胞增殖、迁移、侵袭、管腔形成和小鼠移植瘤模型等功能实验首先探索明确Twist-1相关miRNAs调控的VM及EMT的具体环节、靶基因及其作用机制，与肿瘤血管生成及肿瘤生长和转移的关系，然后选择临床病理标本验证Twist-1、相关miRNAs、靶基因构成的VM及EMT调控网络与临床肿瘤表现的关系，探讨该网络各节点在临床诊断、治疗和预后中的意义。本项目将从miRNAs及其功能通路角度阐明Twist-1对VM及EMT的调控机制，为发展基于血管生成及上皮间充质转变的肿瘤分子诊断、治疗和预后新策略奠定基础。

Twist-1 plays an important role in the process of tumor angiogenesis and epithelial mesenchymal transition ,which also influence the tumorgenesis and development of tumor, but its molecular mechanism need further to clarify. In the previous study,11 kinds of miRNAs those may be directly regulated by Twist-1 were screened .Two kinds of vasculogenic mimicry (VM) related miRNAs and five kinds of epithelial mesenchymal transition (EMT) associated miRNAs were selected. The project plan to the identify the target genes and their mechanism of action of Twist-1 related miRNAs in the process of VM and EMT by cell proliferation assay, m migration assay, invasion assay,3D Matrigel culture and mouse xenograft model to find their relationship with tumor angiogenesis and tumor growth and metastasis.Thereafter , clinical pathology specimens will be used to verify the relationship between Twist-1, related miRNAs and target genes to constitute the regulatory networks of the VM and EMT and clinical oncology performance. Their significance in clinical diagnosis, treatment and prognosis will also be discussed.This project will elucidate the regulatory role and its mechnism of Twist-1 on VM and EMT through the functional pathway of miRNAs .This will lay a foundation for the development of new strategies of molecular tumor diagnosis, treatment and prognosis based on angiogenesis and epithelial mesenchymal transition.