Silencing of DLGAP5 by siRNA significantly inhibits the proliferation and invasion of hepatocellular carcinoma cells

Weijia Liao; Weilong Liu; Qing Yuan; Xing Liu; Ying Ou; Songqing He; Shengguang Yuan; Liling Qin; Qian Chen; Kate Nong; Minghui Mei; Jian Huang

doi:10.1371/journal.pone.0080789

Silencing of DLGAP5 by siRNA significantly inhibits the proliferation and invasion of hepatocellular carcinoma cells

PLoS One. 2013 Dec 4;8(12):e80789. doi: 10.1371/journal.pone.0080789. eCollection 2013.

Authors

Weijia Liao¹, Weilong Liu, Qing Yuan, Xing Liu, Ying Ou, Songqing He, Shengguang Yuan, Liling Qin, Qian Chen, Kate Nong, Minghui Mei, Jian Huang

Affiliation

¹ 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.

Abstract

Background: 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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Carcinoma, Hepatocellular / genetics*
Carcinoma, Hepatocellular / metabolism
Carcinoma, Hepatocellular / pathology
Cell Cycle / genetics
Cell Line, Tumor
Cell Movement
Cell Proliferation
Cell Transformation, Neoplastic / genetics*
Cell Transformation, Neoplastic / metabolism
Cell Transformation, Neoplastic / pathology
DNA Methylation
Female
Gene Expression Regulation, Neoplastic*
Humans
Liver / metabolism
Liver / pathology
Liver Neoplasms / genetics*
Liver Neoplasms / metabolism
Liver Neoplasms / pathology
Male
Middle Aged
Neoplasm Proteins / antagonists & inhibitors
Neoplasm Proteins / genetics*
Neoplasm Proteins / metabolism
Promoter Regions, Genetic
RNA, Small Interfering / genetics
RNA, Small Interfering / metabolism

Substances

DLGAP5 protein, human
Neoplasm Proteins
RNA, Small Interfering

Grants and funding

The authors gratefully acknowledge grant support from the Chinese National Key Program on Basic Research (973 Program, 2010CB529206), the National High Technology Research and Development Program of China (863 Program, 2012AA02A205), the National Natural Science Foundation of China (81260328), the Program of Shanghai Subject Chief Scientist (12XD1421400), and the Guilin Scientific Research and Technological Development Project (20100128-5). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.