首页|期刊导航|中华医学杂志（英文版）|Gene induction and apoptosis in human hepatocellular carcinoma cells SMMC-7721 exposed to 5-aza-2'-deoxycytidine
中华医学杂志（英文版）2007，Vol.120Issue(18)：1626-1631,6.
Gene induction and apoptosis in human hepatocellular carcinoma cells SMMC-7721 exposed to 5-aza-2'-deoxycytidine
Gene induction and apoptosis in human hepatocellular carcinoma cells SMMC-7721 exposed to 5-aza-2'-deoxycytidine
摘要
Abstract
Background Aberrant DNA methylation plays a key role in human carcinogenesis. 5-aza-2'-deoxycytidine inhibits DNA methylation and induces the expression of genes putatively silenced by promoter methylation in vitro. There are few studies of the biological and clinical significance of 5-aza-2'-deoxycytidine in human hepatocellular carcinoma. This study explored the mechanism of 5-aza-2'-deoxycytidine targeting transcriptional repressor complexes affecting global gene expression in hepatocellular carcinoma cell line.Methods High density oligonucleotide gene expression microarrays were used to examine the effects of 5-aza-2'-deoxycytidine treatments on human hepatocellular carcinoma cell line SMMC-7721. The 5' ends of the genes upregulated or downregulated in this manner were compared with BLAST database to determine whether they might have promoter CpG islands. Flow cytometry was used to detect stages of the cell cycle and apoptosis of SMMC-7721 after being treated with 5-aza-2'-deoxycytidine.Results Data obtained 3 days after 4 days of treatment with 5-aza-2'-deoxycytidine showed that more genes were induced in tumorigenic cells including genes that function in cell proliferation, differentiation, regulation of transcription,and cytokine signalling. Approximately 30% of induced genes did not have CpG islands within their 5' regions, suggesting that some genes activated by 5-aza-2'-deoxycytidine may not result from the direct inhibition of promoter methylation.This phenomenon may contribute to a number of upregulated genes involving regulation of transcription in the treated cell. Results showed that 100 μmol/L 5-aza-2'-deoxycytidine blocked cell cycle at S/G2-M phase increasing rate of apoptosis. Notably, we found differential expression of molecular action in the methylation although DNA methyltransferases did not show significant difference in the treated cell line.Conclusion 5-aza-2'-deoxycytidine could restore some silenced genes expression independently of DNA methylation inhibition and expression of DNA methyltransferases.关键词
DNA methylation/ 5-aza-2'-deoxycytidine/ hepatocellular carcinoma/ CpG islandsKey words
DNA methylation/ 5-aza-2'-deoxycytidine/ hepatocellular carcinoma/ CpG islands分类
医药卫生引用本文复制引用
FAN Hong,ZHAO Zhu-jiang,CHENG Yu-chao,SHAN Yun-feng,LU Zhu-hong,ZHANG Jian-qiong,XIE Wei..Gene induction and apoptosis in human hepatocellular carcinoma cells SMMC-7721 exposed to 5-aza-2'-deoxycytidine[J].中华医学杂志（英文版）,2007,120(18):1626-1631,6.基金项目
This work was supported by the grants from National Natural Science Foundation of China (No. 30470950) and Chinese Postdoctoral Science Foundation (No. 2003-2004). （No. 30470950）
