School of Chemical and Biomedical Engineering, Nanyang Technological University, Singapore.
Cancers (Basel). 2010 Sep 16;2(3):1689-704. doi: 10.3390/cancers2031689.
Deleted in Lung and Esophageal Cancer 1 (DLEC1) is a functional tumor suppressor gene (TSG). It has been found to be silenced in a variety of human cancers including hepatocellular carcinoma (HCC). The silencing of DLEC1 can be modulated by epigenetic modifications, such as DNA hypermethylation and histone hypoacetylation. In the case of HCC, hepatitis B virus X protein (HBx) has been implicated in methylation of target promoters resulting in the down-regulation of tumor suppressor genes, which in turn contributes to the development of HCC. In the present study, we first established a cell system in which epigenetic modifications can be modulated using inhibitors of either DNA methylation or histone deacetylation. The cell system was used to reveal that the expression of DLEC1 was upregulated by HBx in a genotype-dependent manner. In particular, HBx genotype A was found to decrease DNA methylation of the DLEC1 promoter. Our results have provided new insights on the impact of HBx in HCC development by epigenetic modifications.
缺失于肺及食管鳞癌 1 号基因（DLEC1）是一个功能性抑癌基因（TSG）。研究发现它在多种人类癌症中都处于沉默状态，包括肝癌（HCC）。DLEC1 的沉默可以通过表观遗传修饰来调控，如 DNA 超甲基化和组蛋白低乙酰化。在 HCC 的情况下，乙型肝炎病毒 X 蛋白（HBx）已被牵连到靶启动子的甲基化，导致肿瘤抑制基因的下调，进而促进 HCC 的发展。在本研究中，我们首先建立了一个细胞系统，使用 DNA 甲基化或组蛋白去乙酰化抑制剂来调节表观遗传修饰。该细胞系统被用来揭示 HBx 以基因型依赖的方式上调 DLEC1 的表达。具体来说，HBx 基因型 A 被发现降低了 DLEC1 启动子的 DNA 甲基化。我们的研究结果为 HBx 通过表观遗传修饰在 HCC 发展中的作用提供了新的见解。
