胆囊癌是胆道系统最常见恶性肿瘤，预后不佳，积极开展相关研究意义重大，长链非编码RNA（lncRNA）是目前胆囊癌研究的新热点。申请者在前期研究中利用胆囊癌肝转移灶与原发灶进行lncRNA芯片筛选，发现lncRNA-LEMD1具有调控胆囊癌细胞侵袭转移的重要作用，并且LEMD1可以与IMP3相互结合并调控其蛋白水平的变化。因此我们提出科学假说LEMD1结合IMP3从而促进胆囊癌细胞侵袭转移。本项目拟进行以下研究：1.明确LEMD1分子特性及在胆囊癌组织及细胞中的生物学特征； 2.确定LEMD1对胆囊癌细胞侵袭转移的调控作用及分子机制； 3.动物体内探索针对LEMD1及相应信号通路的治疗效果； 4.明确LEMD1与胆囊癌发生及预后的关系。

Gallbladder cancer (GBC) is the most common cancer of the biliary tract with an extremely poor prognosis. It is important to study the mechanism of the tumourgenesis of GBC to improve the survival for GBC patients. Long non-coding RNA (lncRNA) has been a new hotspot in the field of GBC research. In our previous work, the differentially expressed lncRNAs between primary GBC tumors and metastatic lesions were identified. A novel lncRNA (lncRNA-LEMD1) has been identified and demonstrated to play an important role in promoting invasion and metastasis of GBC cells. In addition, LEMD1 regulates multiple cancer metastasis related pathways in GBC cell lines. More importantly, LEMD1 was found to bind with IMP3 and promote its protein level. Based on our preliminary results, we hypothesize that LEMD1 promotes the invasion and metastasis in GBC cells via binding IMP3. In our study, we are planning to investigate the molecular features of LEMD1, its role and mechanism of promoting invasion and metastasis in GBC cells, and its potential role as a diagnostic and therapeutic target in GBC.