肝癌转移是影响肝癌患者预后的最主要因素之一，上皮间质转化（EMT）和肿瘤细胞干性获得与肝癌转移密切相关，但其分子机制尚不清楚。本项目在发现miR-491的靶蛋白αB-crystallin水平与肝癌转移呈正相关的基础上，分别应用甲基供体SAM和甲基转移酶抑制剂5-AZA、miR-491激动剂和抑制剂、Tet-on系统调控αB-crystallin水平处理高转移潜能肝癌MHCC97H细胞和无转移潜能肝癌HepG2细胞、并在大鼠肝癌模型及肝癌患者中，在细胞、裸鼠、整体动物及人群多层次，从反向和正向探讨miR-491通过αB-crystallin/β-catenin调控EMT和肿瘤细胞干性获得在肝癌转移中的作用和甲基化水平对其影响以及miR-491和αB-crystallin作为肝癌转移的生物标志和治疗靶点的意义，从而为发现阻滞肝癌转移的早期生物标志和新的治疗措施提供新线索。

The metastasis of hepatocellular carcinoma (HCC) is one of the most important factors associating with the prognosis. Epithelial mesenchymal transition (EMT) and stem cell-like properties of tumor cells are involved in the metastasis of HCC, however, its molecular mechanisms remain unclear. Based on our finding that there is a positive relationship between the level of αB-crystallin, the target protein of miR-491, and the metastasis of HCC, we are going to investigate the roles and mechanisms of αB-crystallin/β-catenin-regulated EMT and stem cell-like properties of tumor cells induced by miR-491 in metastasis of hepatocellular carcinoma as well as the effects of methylation on them using the following three models: (i) Cell model, MHCC97H (high metastatic potential) and HepG2 (no metastatic potential) cells treated by SAM (methyl donor) and 5-AZA (methyltransferase inhibtor), agonists and antagonists of miR-491, or Tet-on system to regulate the level of αB-crystallin, respectively; (ii) The rat model of HCC induced by diethylinitrosamine; (iii) HCC patients of different stages. Our results will be helpful to understand the mechanism of HCC metastasis and indicate miR-491 and αB-crystallin as the diagnosis biomarkers and therapy targets of HCC, which provide new clues for preventing tumor metastasis and guiding new treatment measures of HCC.