Phoomak Chatchai, Silsirivanit Atit, Wongkham Chaisiri, Sripa Banchob, Puapairoj Anucha, Wongkham Sopit
Department of Biochemistry, Khon Kaen University, Khon Kaen, Thailand.
Asian Pac J Cancer Prev. 2012;13 Suppl:101-5.
O-GlcNAcylation, an important O-linked glycosylation of cellular glycoproteins with a single molecule of N-acetylglucosamine (GlcNAc), is involved in regulation of many cellular processes. Alteration of O-GlcNAcylation is associated with the development and progression of many cancers. Here, we demonstrated aberrant O-GlcNAcylation in the cholangiocarcinoma (CCA) using immunohistochemistry of O-GlcNAc modified proteins (OGP), O-GlcNAc transferase (OGT) and N-acetylglucosaminidase (O-GlcNAcase or OGA). OGP expression was low in normal bile ducts corresponding with the low OGT and high OGA expression. In contrast, OGP was strongly expressed in CCA tissues together with the up-regulation of OGT and down-regulation of OGA. Moreover, elevation of O-GlcNAcylation was associated with non-papillary type CCA and poor survival outcome of CCA patients. Our study showed for the first time that O-GlcNAcylation is increased in CCA tissues and is associated with a poor patient outcome. The OGT expression level could be a useful prognostic indicator and inhibition of O-GlcNAcylation might be a therapeutic target for CCA.
O-连接的N-乙酰葡糖胺化（O-GlcNAcylation）是细胞糖蛋白重要的O-连接糖基化修饰，其通过单个N-乙酰葡糖胺（GlcNAc）分子进行，参与许多细胞过程的调控。O-GlcNAcylation的改变与多种癌症的发生和发展相关。在此，我们通过对O-GlcNAc修饰蛋白（OGP）、O-GlcNAc转移酶（OGT）和N-乙酰葡糖胺酶（O-GlcNAcase或OGA）进行免疫组化，证实了胆管癌（CCA）中存在异常的O-GlcNAcylation。在正常胆管中，OGP表达较低，这与低水平的OGT和高水平的OGA表达相对应。相反，在CCA组织中，OGP强烈表达，同时伴随着OGT的上调和OGA的下调。此外，O-GlcNAcylation的升高与非乳头状CCA类型以及CCA患者的不良生存结果相关。我们的研究首次表明，CCA组织中O-GlcNAcylation增加，并且与患者的不良预后相关。OGT表达水平可能是一个有用的预后指标，抑制O-GlcNAcylation可能是CCA的一个治疗靶点。
