lincRNA-UFC1在肝癌发生发展中的作用及其机制探讨

我们预实验证明，lincRNA-UFC1是肝癌复发和预后不良的分子标志物；与miR-34a直接结合，半衰期被缩短从而表达水平降低；与HuR直接结合，进而稳定β-catenin mRNA的表达，促进肝癌细胞的EMT过程。据此我们首次提出：lincRNA-UFC1是肝癌复发转移的关键基因之一。本项目拟通过肿瘤体内外实验及转基因动物实验探讨lincRNA-UFC1在肝癌中的生物学功能；其次利用RIA-Seq、RNA pull down、质谱等技术探讨lincRNA-UFC1促进肝癌复发的分子机制；最后通过临床多中心大样本检测lincRNA-UFC1及其相关蛋白质、miRNA在预警肝癌复发转移及判断预后方面的作用。本项目完成可望揭示lincRNA-UFC1在肝癌发生发展中的作用机制，对肝癌复发转移、预后判断具有重要的理论及临床价值，为肝癌治疗的新靶点提供充分的理论依据。

We have demonstrated that overexpression of lincRNA-UFC1 correlated with tumor recurrence and poor prognosis in patients with hepatocellular carcinoma (HCC). Our data have been proved that miR-34a could bind to lincRNA-UFC1 and decrease its expression level through reducing its half-life. Interaction of lincRNA-UFC1 and HuR leads to stabilization expression of β-catenin, which further promotes the HCC cell epithelial-to-mesenchymal transition (EMT). Based on our preliminary data, we first present that lincRNA-UFC1 is one of the key genes in HCC recurrence. To test the hypothesis, firstly, we will explore the physiological and functional roles of lincRNA-UFC1 in HCC by mouse xenograpt and transgene zebrafish model; secondly, we will deeply understand the mechanism of lincRNA-UFC1 in HCC using RIA-seq，RNA pull down assay and mass spectrometry; last but not least, the effect of lincRNA-UFC1 and its related effectors will be identified by clinical multicenter sample in HCC. From this work, the functional role of lincRNA-UFC1 in HCC progression will be explored and this will be helpful to discover lincRNA-UFC1 as a potential therapeutic target in HCC.