title: Inhibition ofde novoMethyltransferase 3B is a Potential Therapy for Hepatocellular Carcinoma.
abstract: BACKGROUND
  Aberrant epigenetic patterns, including inactivation of tumor suppressor genes due to DNA methylation, have been described in many human cancers. Epigenetic therapeutic is a new and rapidly developing area of tumor treatment because DNA methyltransferase (DNMT) inhibitors can reverse its changes. We attempted to identify potential approach for epigenetic therapy of hepatocellular carcinoma.
  
  
  METHODS
  We knocked down the expression of DNMT 1 or DNMT 3B by siRNA, and inhibited DNA methyltranferases by 5-Aza-2'-deoxycytidine. We used high-density oligonucleotide gene expression microarrays to examine the induced genes in human hepatocellular carcinoma cell line SMMC-7721 after suppressing DNA methyltranferases. The 5' ends of up-regulated genes were analyzed by BLAST database to determine whether they have promoter CpG islands, and then the identical induced genes were compared among different inhibition of DNA methyltranferases.
  
  
  RESULTS
  Our results show that 9 genes were found to be over expressed by more than two-fold induced by DNMT1 siRNA and 5-Aza-CdR, and 30 genes were found to be over expressed by more than two-fold induced by DNMT3B siRNA and 5-Aza-CdR in SMMC-7721. Among them, 76.6% up-regulated genes conjectural contained 5' CpG islands. The DNMT3B siRNA could induce more genes identical to demethylation agent in SMMC-7721.
  
  
  CONCLUSIONS
  DNMT3B might be a new potential target for therapy of hepatocellular carcinoma.
authors.affiliation: Key Laboratory of Developmental Genes and Human Disease, Ministry of Education, Southeast University; Department of Genetics and Development, Southeast University Medical School. 87 Dingjiaqiao, Nanjing 210009, Jiangsu Province, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Fan
authors.affiliation: Key Laboratory of Developmental Genes and Human Disease, Ministry of Education, Southeast University; Department of Genetics and Development, Southeast University Medical School. 87 Dingjiaqiao, Nanjing 210009, Jiangsu Province, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Cheng
authors.affiliation: Key Laboratory of Developmental Genes and Human Disease, Ministry of Education, Southeast University; Department of Genetics and Development, Southeast University Medical School. 87 Dingjiaqiao, Nanjing 210009, Jiangsu Province, China.
authors.forename: Zhu Jiang
authors.initials: ZJ
authors.lastname: Zhao
keywords: 5-Aza-CdR; CpG islands; DNMTs; Epigenetic; Hepatocellular Carcinoma; methylation; siRNA; therapy