葡萄糖磷酸变位酶1(PGM1)与肝细胞癌(HCC)的发生发展和糖代谢密切相关。我们前期报道，HCC中PGM1表达降低的分子机制(Plos Bio，2018)。我们进一步发现，PGM1核表达缺失与HCC发展及预后显著相关。迄今为止，未见HCC中PGM1核表达缺失和机制的报道。前期预实验提示，HCC细胞的PGM1蛋白与RAN蛋白(Ras-related Nuclear protein)具有相互作用，而RAN是输入蛋白β(Importin β)的结合蛋白。另外，我们经过网站预测得到PGM1中的importin α依赖性核定位序列。由此，我们推测RAN、Importin α可能参与PGM1的核定位。据此，本项目拟通过构建Importin α及RAN过表达或敲除的肝癌细胞株，基因编辑小鼠，观察PGM1核定位的变化，明确RAN蛋白通过调控PGM1核表达促进HCC的发生，以期提出HCC发生发展的新机制。

Phosphoglucomutase 1 (PGM1) is closely related to the occurrence and development of hepatocellular carcinoma (HCC) and glycometabolism. We reported earlier that the molecular mechanism of the decreased expression of PGM1 in HCC (Plos Bio, 2018). We further found that the loss of nuclear PGM1 expression was significantly associated with the development and prognosis of HCC. So far, there was no report have been found about loss of Nuclear PGM1 expression in HCC and its mechanism. Preliminary studies indicated that PGM1 protein of HCC cells interacted with RAN protein, and RAN was the binding protein of imported β protein. In addition, the importin α-dependent nuclear localization sequence in PGM 1 was predicted by the website. Therefore, we speculate that RAN and Importin α may be involved in the nuclear localization of PGM1. Accordingly, this project intends to construct Importin α and RAN overexpression or knockout HCC cell lines, gene editing mice, observe the changes of PGM1 nuclear localization, and clarify that RAN protein promotes the occurrence of HCC by regulating PGM1 nuclear expression, in order to propose a new mechanism for the occurrence and development of HCC.