乳腺癌是女性最常见的恶性肿瘤之一，其死因主要是转移和复发。文献报道血管内皮生长因子受体Flt-1表达水平与乳腺癌转移和复发密切相关，但Flt-1在乳腺癌中的功能和作用机制目前还不清楚。在上一个自然基金项目资助下我们证实了miR-10b能够抑制Flt-1的mRNA和蛋白表达；低氧刺激能够促进Flt-1的表达，且miRNAs参与了这一过程。这为Flt-1的功能研究提供了新的线索。本项目拟研究和验证调节Flt-1表达的miRNA分子；阐明低氧环境下miRNAs对Flt-1的调控作用机制，揭示Flt-1对乳腺癌转移和血管生成的影响的机制。在此基础上结合临床资料，探讨Flt-1及其相关的miRNAs与乳腺癌预后和治疗的关系。这些研究将有助于阐明乳腺癌转移和血管生成机制，为乳腺癌的诊断和治疗提供新的实验依据和新的靶点，具有潜在的临床应用价值。

Breast cancer is one of the most common malignant tumor in wowan, the main cause of its death are tumor metastasis and relapse. Flt-1 has been identified as a key component of a 'poor prognosis gene signature' that is strongly predictive of a short interval to distant metastases and Flt-1 expression in primary tumors has been correlated with a high risk of metastasis and relapse.However，the function of Flt-1 in breast cancer remains largely unknown. With supported by National Natural Science Foundation of China，we have previously identified Flt-1 is a potential target of miR-10b,and miR-10b inhibited Flt-1 expression; hypoxic stimulation promoted the expression of Flt-1 in breast cancer;and miRNAs were involved in this process. To examine the function of Flt-1 in breast cancer, we plan to screen and validate miRNAs regulated expression of Flt-1,explore its molecular mechanism by hypoxia and extensively implicated in breast cancer progression.On this basis, we also want to explore the relationship between the Flt-1 and its associated miRNAs and breast cancer prognosis and treatment by clinical data.These studies will help us clarify breast cancer metastasis and angiogenesis process, and provide a new experimental evidence and a new potential target for breast cancer .