肝外胆管癌患者预后极差，且缺乏有效的治疗方案。作为调控自噬及能量代谢的重要分子，肝激酶B1（LKB1）的缺失不但可促进肿瘤发生和转移，也同时能增强双胍类药物的抗癌效果。本研究先由生物信息学方法筛选出LKB1相关内源性竞争RNA(ceRNA)，并初步证实干预这些ceRNA可减少胆管癌细胞在能量应激下的自噬反应。ceRNA通过miRNA与LKB1形成调控网络，我们推测这些ceRNA可能参与LKB1的抑癌机制以及癌细胞在能量应激环境下自噬反应的调控。同时，这些ceRNA的表达缺失也可以作为预测双胍类药物抗癌敏感性的检测靶点。本项目拟通过分子生物学、细胞学和动物实验模型等方法阐明LKB1及ceRNA的调控网络及分子机制；并通过靶基因干预的方法证明LKB1相关ceRNA对胆管癌转移活性、自噬水平及对双胍类药物治疗反应的调控，为双胍类药物抗癌治疗找到靶向预测的参考指标，优选胆管癌症综合治疗的分子靶标。

extrahepatic cholangiocarcinoma is a severe malignancy with poor prognosis. However, patients of this disease seldomly accepted effective treatments. The tumor suppressor liver kinase B1(LKB1),a serine/threonine kinase, is inactivated in many kinds of human tumors including cholangiocarcinoma, which promotes the recurrence and invasiveness of carcinoma. But the loss of LKB1 has been proved to be the target of use of biguanides（BGs）as anti-cancer treatments, because the loss of LKB1 can make the tumor cells more sensitive for drugs targeting energy metabolism like BGs. In this study, we have did many work to investigate the competing endogenous RNA(ceRNA) of LKB1, and to test if interfere of these ceRNA can promote the tumor metastasis, autophagy and sensitivity of cholangiocarcinoma for BGs treatment. Furthermore, we hope to use the cell line experiment and Nude mice into tumor model to study the mechanism of LKB1 and its ceRNA to affect autophagy in response to BGs, as we hypothesis that LKB1 may influence the energy metabolism to transfer cells into autophagy condition to resist the BGs treatment. Here, we aim to make clear the mechanisms of LKB1 and its ceRNA impact on tumor energy metabolism and BGs therapy and it will make a brilliant achievement for gene detection to make clear which pateints are suitable for BGs as targeted medicine for cholangiocacinoma.