β4GalT I在肝癌中的作用及其转录调控研究

项目名称： β4GalT I在肝癌中的作用及其转录调控研究

项目编号： No.30870542

项目类型： 面上项目

立项/批准年度： 2009

项目学科： 轻工业、手工业

项目作者： 江建海

作者单位： 复旦大学

项目金额： 30万元

中文摘要： 肝癌，恶性程度极高，其死亡率与发病率之比高达0.96，居所有癌症之首，号称“#30284;中之王”。研究已经证实在肝癌的发生、发展中伴随着细胞表面糖链结构的改变。β4-半乳糖基转移酶 I (β4GalT I)是最早克隆的糖基转移酶，也是国际上研究最热的一类糖基转移酶，其催化Gal β4GlcNAC糖苷键形成，参与N-聚糖和O-聚糖复合物的合成。本研究发现β4GalT I的mRNA和蛋白表达在肝癌中明显增高，其并受乙肝病毒HBX蛋白调控；通过RNAi干扰抑制β4GalT I的表达将抑制肝癌细胞的细胞周期进程、成瘤能力和侵袭。β4GalT I调控肝癌细胞周期进程、成瘤能力和侵袭。通过研究β4GalT I在肝癌发生、发展中的作用及其转录调控机制，将阐释HBX促肝癌发生、发展的新分子机制。

中文关键词： β4GalT I; 肝癌；转录调控；细胞周期；HBX

英文摘要： The hepatitis B virus-encoded HBx protein contributes to hepatocarcinogenesis with largely unknown. It is widely known that N-linked oligosaccharides on glycoproteins are structurally altered during malignant transformation and these alterations are often associated with malignant transformation of cells. b-1,4-galactosyltransferase I (GalT I) contributes to the biosynthesis of Galb1, 4GlcNAc structure in the outer chain moieties of N-glycans. Here, we found that GalT I was highly expressed in hepatocellular carcinoma and transcriptionally up-regulated by HBx, and functioned as a positive growth regulator in hepatoma cells. Furthermore, decreasing the expression of GalT I in hepatoma cells reduced the ability of tumor formation in vivo and the ability of hepatoma cell invasion, and inhibited HBx-induced cell cycle progression. Thus, HBx-induced GalT I expression might contribute to HBx-mediated HCC development and progression.

英文关键词： β4-Galactosyltransferase I; Liver cancer; Cell cycle; HBx; Transcriptional regulation