现阶段认为原发性肝癌很可能起源于癌变的成体肝干细胞。我们通过上调Bmi1的表达诱导大鼠成体肝干细胞（卵圆细胞）在裸鼠体内形成肝细胞癌，并发现在此过程中Wnt信号通路激活，并且DKK1表达升高。DKK1是调控Wnt信号通路的关键蛋白。下调高表达Bmi1的卵圆细胞中DKK1表达后，其体外增殖、克隆形成、迁移和侵袭能力下降显著，并且Wnt1和β-catenin表达下降。在以上基础上我们假设：Bmi1通过调控DKK1激活 Wnt通路诱导大鼠成体肝干细胞转化为肝细胞癌。本研究采用基因转染技术，分别下调或上调高表达Bmi1卵圆细胞和正常卵圆细胞中DKK1的表达，然后检测：1 .卵圆细胞在体外增殖、克隆形成、迁移/侵袭、耐受化疗药物能力以及在裸鼠体内成瘤能力；2. Bmi1调控DKK1激活Wnt通路的分子机制。本研究揭示关键基因/信号通路在成体肝干细胞癌变中的作用，为肝细胞癌特异靶向治疗提供理论依据。

At the present stage, we think that hepatocellular carcinoma may originate from liver progenitor cells. In our experiment, Bmi1 were conducted in rat liver progenitor cells (OC3) through gene transfection technique. It showed that forced expression of Bmi1 accelerated the carcinogenesis of OC3 in nude mice. And at the same time, we found that Wnt signal pathway activated and DKK1 expression of OC3 cells increased because of the enhanced Bmi1 expression. DKK1 exert important modulatory effect on Wnt signal pathways. To be specific, loss-of-function assay of DKK1 in high-expression Bmi1 of OC3 showed that down-regulation of DKK1 has a positive correlation with the proliferation in vitro, colony-forming efficiency, invasive ability and migration ability of OC3. Meanwhile, the expressions of Wnt1 and β-catenin are down-regulated. Therefore, we presume that Bmi1 can activate Wnt signal pathway and promote the carcinogenesis of OC3 by regulating DKK1 expression.In this research, we use gene transfection technique to down-regulate or up-regulate the expression of DKK1 in high expression and normal expression of OC3 respectively. Then we will detect the following two aspects: 1 proliferation, colony formation and migration of OC3 in vitro; 2 Molecular mechanisms in Wnt signal pathway induced by Bmi1 on DKK1 expression.This research reveals the effect of the key gene and signal pathway on carcinogenesis of liver progenitor cells. So it lays a theoretical basis for the specific targeted therapy of hepatocellular carcinoma.