LncRNA-MALAT1调控FGF23/β-catenin信号通路影响子宫肉瘤侵袭转移的机制研究

子宫肉瘤虽然罕见，但侵袭性高，易远处转移及复发，预后极差。但其复发转移的分子机制尚不清楚。本课题组前期研究发现MALAT1对子宫肉瘤细胞株的侵袭转移有抑制作用，并且与FGF23及β-catenin信号通路有关，我们推测MALAT1能通过调控FGF23及β-catenin信号通路参与EMT介导的子宫肉瘤的侵袭转移。本项目以子宫肉瘤细胞株MES-SA、SK-UT-1为研究对象，通过构建MALAT1、FGF23过表达及干扰载体，体内外实验证实MALAT1参与EMT介导的US侵袭转移，并检测β-catenin信号通路、EMT标志物等表达情况。并利用荧光素酶报告系统、RNA pull-down及质谱分析技术鉴定MALAT1与FGF23的作用关系。最后，通过患者组织标本验证。本研究不但能深入了解MALAT1参与US侵袭转移的具体机制，而且有望为US的治疗提供新的候选靶点。

Uterine sarcoma (US) is a rare, aggressive and lethal gynecological cancer in women of all ages that accounts for 3-7% of all uterine cancers, presenting a higher incidence in women between 50 and 70 years old. Uterine sarcomas include leiomyosarcoma, carcinosarcoma, and endometrial stromal sarcoma according to the common histological types. The prognosis of uterine sarcomas remains poor. Regardless of which therapy can be used for uterine sarcoma, the response to treatment is unsatisfactory. However, the molecular mechanism of relapse and metastasis of US is unclear. Long non‑coding RNA metastasis associated with lung adenocarcinoma transcript 1 (MALAT1) has been reported to serve tumor‑promoting roles. Our previous research works found that silencing of MALAT1 inhibited migration, invasion when FGF23 and β-catenin expression levels were decreased. FGF23 directly bound to MALAT1 RNA by Bioinformatics and RNA immunoprecipitation (RIP) assay. Based on molecular biology, transcriptome sequencing, bioinformatics, and proteomics, we further probed into the molecular mechanism of lncRNA MALAT1/FGF23/β-catenin Pathway on the regulation of migration, invasion and epithelial‑mesenchymal transition of US in cell and animal models, and it may serve as novel clinical therapeutic targets for US.