上皮间质转化(EMT)是结直肠癌等恶性肿瘤转移的关键所在。我们研究发现miR-519可抑制结直肠癌的发生发展，但其调控机制尚未阐明。研究表明lncRNA-XIST可促进多种恶性肿瘤的侵袭转移。预实验结果显示：XIST在结直肠癌组织中高表达，且与miR-519的表达呈负相关；XIST存在miR-519的结合位点，且下调XIST可抑制结肠癌细胞中miR-519潜在靶基因TAB3的表达；下调 XIST可抑制结直肠癌细胞发生EMT，并降低细胞的侵袭转移能力。据此我们推测：XIST通过竞争性结合miR-519上调TAB3表达进而促进结直肠癌EMT和侵袭转移。本项目通过构建稳定转染细胞株及裸鼠肿瘤在体模型，明确XIST对结直肠癌EMT和侵袭转移的影响。结合生物信息学分析，并通过分子生物学技术阐明XIST调节miR-519/TAB3轴的分子机制。本研究结果将为阐明结直肠癌的侵袭转移机制提供新的理论依据.

Epithelial-mesenchymal transition (EMT) is key to colorectal cancer (CRC) metastasis. Our previous study have confirmed that miR-519 inhibits the progression of CRC, but its regulatory mechanism is unclear. The previous studies have showed that lncRNA-XIST play an important role in the occurrence and development of tumor. Our preliminary studies suggest that XIST was significantly elevated in the CRC tissues, and the expression of XIST was negatively correlated with miR-519 expression in CRC tissues. XIST knockdown could inhibit EMT, migration and invasion of the CRC cells. In addition, bioinformatics analysis revealed that XIST has the binding sites of miR-519, and TAB3 may be the downstream target gene of miR-519. Furthermore, knockdown of XIST could reduce the expression of TAB3 in CRC cells. Therefore, we speculated that XIST promotes the EMT and metastasis of CRC mediator of by acting as a ceRNA (competing endogenous RNA) for miR-519, thereby increasing expression of its target TAB3. To test this hypothesis and investigate the mechanism of its action, we will construct stale stable transfection cell lines and in vivo tumor model, observe the effect of XIST on EMT and metastasis in CRC. Furthermore, we will clarify the mechanism through which XIST regulates miR-519/TAB3 axis by bioinformatics analysis and molecular biological methods. These results will provide the new theoretical basis for clarifying the mechanism of CRC invasion and metastasis.