Claudin-Low型三阴性乳腺癌(TNBC)恶性程度高、预后差。研究发现，RNA结合蛋白U2AF65异常表达与肿瘤相关。前期证实：1.在U2AF65低表达的Claudin-Low型TNBC细胞中，上调U2AF65能抑制细胞迁移、侵袭；2.调控HCG18的表达可改变TNBC细胞形态；3.miR-155-5p过表达激活乳腺癌增殖通路。4.软件预测发现HCG18、miR-155-5p、ELF4之间存在联系。通过系列工作进一步提出U2AF65/HCG18/miR-155-5p/ELF4通路调控claudin-Low型TNBC细胞迁移和侵袭的工作假说。为证实这一假说，项目将采用RT-PCR、免疫共沉淀、荧光素酶基因报告实验等技术，明确潜在调控通路各位点的相互作用方式，观察其对迁移和侵袭等肿瘤生物学行为的影响。项目将为TNBC临床病情评估与风险预测，及潜在的靶向治疗提供新的思路和方向。

Claudin-low subtype of triple negative breast cancer (TNBC) has a high degree of malignancy and poor prognosis. Study reveals that U2AF65, an RNA-binding protein, is relative to cancer. Our previous work confirmed that: 1.Claudin-low subtype of TNBC represented a lower expression of U2AF65, and upregulating U2AF65 could inhibit cell invasion and migration. 2.Regulating the expression of HCG18 can change the morphology of cell.3. Overexpression of miR-155-5p activates the proliferation of breast cancer. 4. Online application predicts the relationship between HCG18, miR-155-5p and ELF4. Thus, a series of subsequent experiments were performed and the hypothesis of U2AF65/HCG18/miR-155-5p/ELF4 signaling pathway in regulating claudin-low TNBC migration and invasion was further proposed. To explore this hypothesis, the interactions and characteristics between each potential regulatory point, and characteristics of tumor biological behavior, including migration and invasion will be confirmed and observed, through overexpression/silence of each point in pathway and application of inhibitor/agonist, by various molecular biology technology, such as RT-PCR, immune coprecipitation, luciferase report gene molecular biology technology. The implelmentation of the project will provide new ideas and directions for clinical assessment and risk prediction, as well as potential targeted therapy.