恶性胸腔积液（MPE）是肺癌预后不良标志，治疗手段有限。研究显示血管生成素2（Ang2）通过结合酪氨酸激酶型受体2（Tie2）参与淋巴管产生，在恶性胸腔积液发展过程中发挥关键作用。课题组前期研究发现，miR-93在MPE患者预后较好组胸腔积液中显著高表达，数据库预测及分子实验证实miR-93参与调控Ang2表达。因此我们推测：miR-93可能通过调控Ang2抑制淋巴管形成，并抑制MPE产生。本项目拟通过分子和细胞水平实验探究miR-93调控Ang2/Tie2轴在淋巴管形成过程中的功能，解析MPE发生机制，阐明miR-93在MPE形成中的调控作用；通过构建MPE动物模型，合成化学修饰miR-93激动剂和拮抗剂，观察胸腔内局部给药对MPE转归的影响，评价其潜在治疗价值。期望从转录后水平这个新视角，拓展对MPE产生机制的认识，为抗淋巴管生成及淋巴道转移治疗提供理论基础，探索MPE局部治疗新策略。

The presence of malignant pleural effusion (MPE) is an important sign of recurrent or advanced malignancies and has short life expectancy. In spite of its frequent occurrence in clinical arena, limited studies have been reported on the management of MPE and patients in general have little improvement from available therapies. Angiotensin 2 (Ang2) binding to Tie2 receptor is involved in angiogenesis and lymphangiogenesis. Studies of the molecular mechanisms of MPE have found that new blood and lymph vessel formation are important in the development of MPE. Our previous studies have found that, for lung adenocarcinoma patients, the level of miR-93 in MPE was significantly higher in good prognosis group than that in poor prognosis group. Database prediction and molecular experiments confirmed that miR-93 involved in regulating the expression of Ang2. Therefore, we hypothesize that miR-93 may regulate the expression of Ang2 and implicate the development of MPE by inhibiting angiogenesis and lymphangiogenesis. In the current study, we focused on the targeted regulation of miR-93 to Ang2 / Tie2 axis and further investigate the role of miR-93 in MPE pathogenesis and MPE control. Through the establishment of MPE nude mice model, we try to evaluate therapeutic effects of miR-93 against MPE. Through this project, we expect to expand the knowledge of post-transcriptional regulation mechanism of MPE, reveal the role of miR-93 in the development of MPE and build the theoretical basis of miRNA gene therapy.