Brief Article
Copyright ©2012 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Jun 7, 2012; 18(21): 2719-2726
Published online Jun 7, 2012. doi: 10.3748/wjg.v18.i21.2719
Aberrant methylation and downregulation of sall3 in human hepatocellular carcinoma
Xue-Xi Yang, Jing-Zhe Sun, Fen-Xia Li, Ying-Song Wu, Hong-Yan Du, Wei Zhu, Xiang-Hong Li, Ming Li
Xue-Xi Yang, Fen-Xia Li, Ying-Song Wu, Hong-Yan Du, Ming Li, School of Biotechnology, Southern Medical University, Guangzhou 510515, Guangdong Province, China
Jing-Zhe Sun, Department of VIP ward, 306th Hospital of People's Liberation Army, Beijing 100101, China
Wei Zhu, Department of Toxicology, Guangzhou Center for Disease Control and Prevention, Guangzhou 510440, Guangdong Province, China
Xiang-Hong Li, Department of Hepatobiliary Surgery, Nanfang Hospital, Guangzhou 510515, Guangdong Province, China
Author contributions: Yang XX and Sun JZ contributed equally to this work; Li M, Yang XX, Zhu W and Li XH designed the research; Sun JZ, Wu YS and Du HY performed the research; Sun JZ and Li FX analyzed the data; and Yang XX, Sun JZ and Li M wrote the paper.
Supported by Key Programs for Science and Technology Development of Guangzhou, No. 2008A1-E4151; and the National High Technology Research and Development Program of China, No. 2006AA02A311
Correspondence to: Ming Li, Professor, School of Biotechnology, Southern Medical University, Guangzhou 510515, China. mingli2006_2006@126.com
Telephone: +86-20-61648550 Fax: +86-20-61648554
Received: September 9, 2011
Revised: October 27, 2011
Accepted: April 28, 2012
Published online: June 7, 2012
Abstract

AIM: To investigated whether sall3 transcription was regulated by promoter CpG island hypermethylation in hepatocellular carcinoma (HCC).

METHODS: The cell lines Huh7, HepG2, SK-HEP1, SMMC7721, Bel7402, QGY7703 and a cohort of 38 HCC tissue specimens and corresponding nontumorous tissues were subjected to analysis for sall3 promoter CpG island methylation and mRNA transcription. sall3 promoter CpG island methylation levels were determined using the MassARRAY platform and mRNA transcription levels of the gene were detected by quantitative real-time polymerase chain reaction.

RESULTS: The levels of sall3 mRNA were decreased by more than twofold in 33 of 38 tumor tissues compared to adjacent noncancerous tissues. Among these 33 tumor tissues with lower levels of sall3 mRNA, 24 showed higher levels of methylation. Based on these results, we hypothesized that the decrease in sall3 mRNA transcription level was likely due to promoter CpG island hypermethylation. Changes in sall3 mRNA transcription and promoter CpG island methylation were determined in the above six cell lines after treatment with 0, 0.1, 0.5 and 2.5 μmol 5-aza-2-deoxycytidine, a demethylating agent. Promoter CpG island methylation levels decreased in a dose-dependent manner in all six cell lines, while the mRNA transcription level increased dose-dependently in Huh7, HepG2, SK-HEP1 and SMMC7721 cells and irregularly in Bel7402 and QGY7703 cells.

CONCLUSION: These results indicated that promoter CpG island hypermethylation contributes to the downregulation of sall3 mRNA transcription in HCC.

Keywords: Hepatocellular carcinoma; sall3; Aberrant methylation; Down regulation mRNA transcription