Liao Weijia, Liu Weilong, Yuan Qing, Liu Xing, Ou Ying, He Songqing, Yuan Shengguang, Qin Liling, Chen Qian, Nong Kate, Mei Minghui, Huang Jian
Institute of Hepatobiliary Surgery, Hospital Affiliated of Guilin Medical University, Guangxi Key Laboratory of Molecular Medicine, People's Republic of China in liver injury and repair, Hepatology Institute of Guilin Medical University, Guilin, Guangxi Zhuang Autonomous Region, China.
PLoS One. 2013 Dec 4;8(12):e80789. doi: 10.1371/journal.pone.0080789. eCollection 2013.
The dysregulation of oncogenes and tumor suppressor genes plays an important role in many cancers, including hepatocellular carcinoma (HCC), which is one of the most common cancers in the world. In a previous microarray experiment, we found that DLGAP5 is overexpressed in HCCs. However, whether the up-regulation of DLGAP5 contributes to hepatocarcinogenesis remains unclear.
METHODOLOGY/PRINCIPAL FINDINGS: In this study, we showed that DLGAP5 was significantly up-regulated in 76.4% (168 of 220) of the analyzed HCC specimens when compared with adjacent liver tissue. DLGAP5 overexpression was evident in 25% (22 of 88) of the HCC specimens without AFP expression, suggesting that DLGAP5 may be a novel biomarker for HCC pathogenesis. The silencing of DLGAP5 gene expression by RNA interference significantly suppressed cell growth, migration and colony formation in vitro. The expression level of DLGAP5 was also found to be related to the methylation level of its promoter in the HCC specimens.
CONCLUSIONS/SIGNIFICANCE: Taken together, these data suggest that the expression of DLGAP5 is regulated by methylation and that the up-regulation of DLGAP5 contributes to HCC tumorigenesis by promoting cell proliferation.
癌基因和肿瘤抑制基因的失调在包括肝细胞癌（HCC）在内的许多癌症中起重要作用，肝细胞癌是世界上最常见的癌症之一。在先前的一项微阵列实验中，我们发现DLGAP5在肝癌中过表达。然而，DLGAP5的上调是否有助于肝癌发生仍不清楚。
方法/主要发现：在本研究中，我们发现与相邻肝组织相比，在76.4%（220个中的168个）分析的肝癌标本中DLGAP5显著上调。在25%（88个中的22个）无甲胎蛋白表达的肝癌标本中DLGAP5过表达明显，提示DLGAP5可能是肝癌发病机制的一种新型生物标志物。通过RNA干扰沉默DLGAP5基因表达可显著抑制体外细胞生长、迁移和集落形成。还发现肝癌标本中DLGAP5的表达水平与其启动子的甲基化水平有关。
结论/意义：综上所述，这些数据表明DLGAP5的表达受甲基化调控，且DLGAP5的上调通过促进细胞增殖有助于肝癌的发生。
