长非编码RNA UICLM在结直肠癌肝转移中的作用及其分子机制

Liver metastasis is one of the leading causes of death in colorectal cancer (CRC ) patients. Previously, We found that microRNA-214 inhibits CRC liver metastasis by regulating FGFR1 expression (Chen DL et al., Hepatology, 2014). In this project, We performed lncRNA microarray to identify the differentially expressed lncRNA between CRC tissues with and without liver metastasis and found lncRNA UICLM was significantly up-regulated in tissues with liver metastasis. Moreover, up-regulation of UICLM induces epithelial-mesenchymal transition (EMT), and promotes the migration and invasion of CRC cells. Futhermore, We found UICLM activated the Akt/GSK-3β/Snail signaling pathway in CRC cells. On this basis, We intend to carry on this project, to explore the the role and detailed molecular mechanism of UICLM in the development of CRC liver metastasis by using CRC tissue samples, cell lines and animal models. Completion of this study will for the first time reveal the role of UICLM in CRC liver metastasis, this may provide new insights into the treatment and prevention for CRC liver metastasis.

肝转移是结直肠癌患者最主要的死亡原因之一。我们前期发现microRNA-214可靶向调控FGFR1的表达从而抑制结直肠癌肝转移的发生和发展（Chen DL et al., Hepatology, 2014），本项目拟进一步研究长非编码RNA（lncRNA）在结直肠癌肝转移中的作用。我们应用lncRNA芯片检测有肝转移和无肝转移的结直肠癌组织中的lncRNA表达谱，发现lncRNA UICLM在有肝转移的结直肠癌组织中显著上调；上调UICLM可以诱导肿瘤细胞发生上皮-间质转化，增加细胞的迁移和侵袭能力；UICLM可激活Akt/GSK-3β/Snail通路。基于此，本项目拟在结直肠癌临床组织标本、细胞系及动物接种模型中，深入探索UICLM对结直肠癌肝转移发生发展的影响及其调控的精确分子机制。本项目的完成，将首次阐明UICLM在结直肠癌肝转移中的作用，为结直肠癌肝转移的防治提供新的理论依据。

肝转移是结直肠癌患者最主要的死亡原因之一。我们前期发现microRNA-214可靶向调控FGFR1的表达从而抑制结直肠癌肝转移的发生和发展。长非编码RNA在结直肠癌肝转移中的作用机制未明。我们应用lncRNA芯片检测有肝转移和无肝转移的结直肠癌组织中的lncRNA表达谱，发现lncRNA UICLM在有肝转移的结直肠癌组织中显著上调；上调UICLM可以诱导肿瘤细胞发生上皮-间质转化，增加细胞的迁移和侵袭能力，并在动物模型中增加结直肠癌细胞肝转移的能力。进一步研究发现，上调的lncRNA UICLM可以通过作为miR-215的分子海绵调控ZEB2的表达。本研究的完成，明确了长非编码RNA在结直肠癌肝转移的作用和机制，为结直肠癌肝转移防治提供了新的思路和策略。