胆囊癌预后极差，在我国发病率居世界前列。长链非编码RNA（lncRNA）是肿瘤研究的热点，但涉及胆囊癌的研究少且局限。我们前期研究发现一条尚未报道的lncRNA“LINC01589”在胆囊癌组织中表达显著下调，表达水平和预后以及基因组拷贝数相关。明确其基本特征和基因组定位后，体内外实验发现敲除LINC01589能促进胆囊癌细胞侵袭转移，反之则抑制。分子机制研究表明：敲除LINC01589能显著提高其直接结合蛋白LASP1的磷酸化水平、促进后者入核；其抑癌作用与PI3K/AKT信号通路相关。本项目拟通过体内外实验，在细胞与分子水平深入研究LINC01589对胆囊癌细胞侵袭转移能力的影响、LINC01589与LASP1结合的分子基础、LINC01589/LASP1轴对靶基因及下游信号通路PI3K/AKT的调控机制，旨在阐明LINC01589在胆囊癌侵袭转移中的功能及分子机制，为治疗提供新靶点。

Gallbladder cancer (GBC) has a very poor prognosis. The incidence of GBC in China ranks the world. Recently, mounting evidences have shown that long non-coding RNAs (lncRNAs) are hot topic in cancer research. Yet, few studies about lncRNAs and GBC were reported. In our previous study, an unreported lncRNA "LINC01589" was found significantly down-regulated in gallbladder cancer tissue, and the expression level of it was associated with prognosis and the number of copies of the genome. After defining its basic characteristics and genomic localization, it was found that the knockout of LINC01589 could promote the invasion and metastasis of gallbladder cancer cells in vitro and in vivo. The molecular mechanism study showed that the knockout of LINC01589 significantly enhanced the phosphorylation level of the direct binding protein LASP1 and promoted it transportation to the nucleus. The antitumor effect of LINC01589 is correlated with PI3K/AKT signaling pathway. This project will deeply explore the effect of LINC01589 on invasion and metastasis of gallbladder cancer cell, the molecular basis of LINC01589 combing with LASP1 and the regulatory mechanism of LINC01589/LASP1 axis targeting genes and downstream signal pathway PI3K/AKT from the view of cell and molecular level in vivo and in vitro. The aim of this study is to clarify the function and molecular mechanism of LINC01589 in GBC invasion and metastasis, which could provide new targets for therapy.