SATB1竞争结合miRNA-200a-3p调控ZEB1表达影响子宫内膜癌转移的机制研究

子宫内膜癌转移严重影响病人预后且机制不明。前期证实特异性核基质结合区结合蛋白1（SATB1）在内膜癌中表达与淋巴转移相关。预实验：相对于病灶局限于子宫的内膜癌组织，病灶超出子宫的癌组织SATB1高表达；生信预测E-盒结合锌指蛋白1（ZEB1）与SATB1呈mRNA表达正相关；细胞系中敲减或过表达SATB1，ZEB1表达分别降低或提高；生信及Luciferase证实miRNA-200a-3p可靶向结合SATB1 mRNA和ZEB1 mRNA。由此假设SATB1 mRNA作为ceRNA与ZEB1 mRNA竞争结合miRNA-200a-3p，导致ZEB1上调，促进上皮间质转化（EMT）而使内膜癌转移增强。项目拟利用分子生物学实验验证三者ceRNA关系，运用体内外实验探索该关系对内膜癌EMT和转移的影响，从ceRNA调控水平探索EMT相关内膜癌转移机制，为指导临床判断内膜癌进展和促进预后奠定基础。

Endometrial cancer metastasis seriously affects the prognosis of patients and the mechanism is unknown. In our previous study, we have confirmed that the expression of Special AT-rich binding protein 1 (SATB1) is closely related to lymphatic metastasis in endometrial cancer. Then the results of pre-experiments have shown that SATB1 is higher expressed in endometrial cancer tissues whose lesions are beyond the uterus than the ones whose lesions are confined to the uterus. In addition, we predicted that it had a positive correlation between the expression of Zinc finger E-box binding homeobox 1 (ZEB1) mRNA and SATB1 mRNA by bioinformatics. Moreover, knock-down or over-expression of SATB1 led to the decreased or increased ZEB1 expression in cell lines, respectively. Furthermore, using bioinformatics prediction and Luciferase experiments, we got the results that miRNA-200a-3p could target SATB1 mRNA and ZEB1 mRNA. Therefore, it is hypothesized that SATB1 mRNA, as a ceRNA, may competitively target miRNA-200a-3p with ZEB1 mRNA and cause up-regulation of ZEB1, which further promotes epithelial-to-mesenchymal transition (EMT) and enhances the ability of endometrial cancer metastatic. In order to validate this hypothesis, we are going to verify the ceRNA relationship among SATB1 mRNA, miRNA-200a-3p and ZEB1 mRNA by molecular biology experiment. Next, we will apply experiments in vivo and in vitro to check the effect of the relationship on EMT and metastatic ability in endometrial cancer, which explore the mechanism of EMT-related endometrial cancer metastasis from the level of ceRNA regulation. All of these conclusions are beneficial to laying a foundation for guiding gynecologists to judge the degree of endometrial cancer progression and promote prognosis.