选择性剪接CD44调控乳腺癌细胞干性，与乳腺癌侵袭转移密切相关。但剪接因子NOVA1调控CD44的具体功能和机制仍不清楚。前期研究表明：①剪接因子NOVA1在乳腺癌细胞(尤其是三阴性乳腺癌)中的表达显著下降，NOVA1可抑制乳腺癌细胞的侵袭能力(体外)；②CD44为NOVA1下游潜在靶基因。本项目拟回答以下科学问题：1.表达：剪接因子 NOVA1和CD44选择性剪接体的表达是影响肿瘤进展和患者生存预后的重要因素；2.功能：NOVA1与CD44选择性剪接体的功能(体内和体外)；3. 机制：NOVA1参与乳腺癌细胞EMT表型转化过程中CD44的剪接表达从而影响肿瘤细胞的侵袭与转移；4.转化：PPARγ激动剂可诱导NOVA1表达，药物诱导NOVA1的表达从而调控乳腺癌细胞EMT表型转化抑制肿瘤的侵袭与转移。本项目旨在阐明 NOVA1通过调控 CD44选择性剪接抑制乳腺癌转移的功能和分子机制。

Metastasis is the main cause of death in breast cancer patients, and the splicing of CD44 regulates the stemness of breast cancer cells, which is closely related to breast cancer invasion and metastasis. However, the function and mechanism of splicing factors NOVA1 on regulating CD44 remain unclear. Previous studies have shown that: ①The expression of splicing factor NOVA1 in breast cancer cells (especially triple-negative breast cancer) is significantly reduced, and overexpression of NOVA1 can inhibit the invasion ability of breast cancer cells (in vitro); ②CD44 is a potential downstreamtarget of NOVA1. This project intends to answer the following points: 1. Metastasis is the main cause of death in breast cancer patients, and the splicing of CD44 regulates the stemness of breast cancer cells, which is closely related to breast cancer invasion and metastasis. However, the function and mechanism of splicing factors NOVA1 on regulating CD44 remain unclear. Previous studies have shown that: ①The expression of splicing factor NOVA1 in breast cancer cells (especially triple-negative breast cancer) is significantly reduced, and overexpression of NOVA1 can inhibit the invasion ability of breast cancer cells (in vitro); ②CD44 is a potential downstream target of NOVA1. This project intends to answer the following points: 1. Expression: The expression of the NOVA1 and CD44 in breast cancer, and the correlation between expression and survival in breast cancers; 2. Function: The function of NOVA1 and the alternative spliceosomes of CD44 (in vivo and in vitro); 3. Mechanism: NOVA1 participates in the splicing expression of CD44 during the EMT phenotype transformation of breast cancer cells to affect the invasion and metastasis of tumor cells; 4. Transformation: PPARγ agonists can induce the expression of NOVA1 to regulate the EMT phenotype transformation of breast cancer cells and thus inhibit tumor invasion and metastasis. This project aims to clarify the function and molecular mechanism of NOVA1 that inhibit breast cancer metastasis by regulating the alternative splicing of CD44.