PGM1基因在肝细胞癌中的抑癌功能及分子机制

项目名称： PGM1基因在肝细胞癌中的抑癌功能及分子机制

项目编号： No.81201937

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 肿瘤学2

项目作者： 金光植

作者单位： 中国人民解放军第二军医大学

项目金额： 23万元

中文摘要： 前期工作中我们利用蛋白组学方法，发现磷酸葡萄糖变位酶1（PGM1）基因在肝细胞癌（HCC）癌前病变中高表达，HCC组织中低表达，并与HCC患者的预后显著相关。据此，我们认为PGM1是HCC的一种重要的抑癌基因，目前对该基因的功能研究尚未见报道。本研究首先在细胞学水平上利用RNAi和过表达技术，改变PGM1的表达量，探讨对HCC细胞的生长、侵袭、凋亡等细胞学功能的影响，并采用裸鼠种植瘤模型进行体内功能验证；在分子水平上采用PCR-SSCP技术检测PGM1编码区外显子基因突变位点，采用MSP-PCR法检测PGM1 DNA启动子区的甲基化，探讨PGM1在HCC中被下调的分子机制。同时将采用常规免疫组化方法进行前瞻性研究，对500例HCC组织进行PGM1检测，确定PGM1的HCC诊断效率。通过本项目阐述PGM1在HCC发生发展中的作用机制，为提高HCC的诊断效率和评估预后提供新的分子标志物。

中文关键词： PGM1；细胞功能；抑癌基因；；

英文摘要： Recently, by using iTRAQ-2DLC-ESI-MS/MS technique, we identified 147 proteins, including 52 proteins up-regulated and 95 proteins down-regulated in small Hepatocellular Carcinoma (sHCC), and found that Phosphoglucomutase-1 (PGM1) can be served as candidate immunohistochemistry markers for distinction of small HCC from DN. PGM1 belongs to the phosphohexose mutase family and participates in both the breakdown and synthesis of glucose. PGM1 mainly expressed in cytoplasm as monomer and binds magnesium ion as cofactor. In addition, defects in PGM1 is the cause of glycogen storage disease type 14 (GSD14). GSD14 related metabolic disorder resulting in a myopathy characterized by exercise-induced intolerance with episodes of rhabdomyolysis, normal elevation of lactate, and hyperammonemia on a forearm-exercise test. It was a first proposal that PGM1 protein can be used as immunohistochemistry markers. However, how the PGM1 related and participate to the biological behavior of HCC cell and hepatocarcinogenesis has not yet been studied. Moreover, in the preliminary experiment, we found that PGM1 highly expressed in MHCC-97L and lowly expressed in HCC-LM3. In addition, PGM1 expression in HCC tissue showed significant prognostic value from our preliminary experiment. From these results, we hypothesize that PGM1 may serve a

英文关键词： PGM1；cellular function；cancer suppressor gene；；