title: Aberrant CpG island hypermethylation and down-regulation of Oct-6 mRNA expression in human hepatocellular carcinoma.
abstract: BACKGROUND
  Aberrant CpG island hypermethylation is a major epigenetic mechanism that can inactivate the transcription of cancer-related genes.
  
  
  OBJECTIVE
  This study aimed to investigate whether Oct-6 transcription was regulated by CpG island methylation in hepatocellular carcinoma (HCC).
  
  
  METHODS
  Quantitative real-time PCR and the MassARRAY platform (Sequenom) were employed in 38 HCC tissues samples and four cell lines.
  
  
  RESULTS
  The levels of Oct-6 mRNA were decreased by more than twofold in 31 of 38 tumor tissues compared to that of adjacent non-cancerous tissues. Among the 31 tumor tissues with lower levels of Oct-6 mRNA, 17 tumor tissues also had higher methylation levels in Oct-6 CpG island. Based on these results, we hypothesized that CpG island hypermethylation may down-regulate Oct-6 mRNA expression in HCC. To confirm this hypothesis, we also analyzed the changes in Oct-6 mRNA expression and CpG island methylation in four HCC cell lines (Huh7, Bel-7402, HepG2 and SMMC-7721) after treatment with 0.1, 0.5 and 2.5 μM 5-Aza-2-deoxycytidine (5-Aza-CdR), a demethylating agent. The results demonstrated that the CpG island methylation levels decreased and Oct-6 mRNA levels increased in a dose-dependent manner in both Huh7 and Bel7402 cells, but there were only slight changes in HepG2 cell. Interestingly, there were no significant alterations of Oct-6 mRNA levels observed in SMMC7721 cell; although lower levels of CpG island methylation were detected after treatment with 5-Aza-CdR.
  
  
  CONCLUSIONS
  Our study shows that CpG island hypermethylation contributes to down-regulation of Oct-6 mRNA expression in HCC.
authors: School of Biotechnology, Southern Medical University, Guangzhou, 510515, People's Republic of China.
authors: Jing-Zhe
authors: JZ
authors: Sun
authors: Xue-Xi
authors: XX
authors: Yang
authors: Xiang-Hong
authors: XH
authors: Li
authors: Wei-Wen
authors: WW
authors: Xu
authors: Ying
authors: Y
authors: Wang
authors: Wei
authors: W
authors: Zhu
authors: Ming
authors: M
authors: Li
mesh_terms: D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D018899:CpG Islands / Q000235:genetics*; D019175:DNA Methylation / Q000187:drug effects / Q000235:genetics*; D004273:DNA, Neoplasm / Q000235:genetics*; D000077209:Decitabine; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D044127:Epigenesis, Genetic / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D050816:Octamer Transcription Factor-6 / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*
chemical_list: D000964:Antimetabolites, Antineoplastic; D004273:DNA, Neoplasm; D004791:Enzyme Inhibitors; D012333:RNA, Messenger; D050816:Octamer Transcription Factor-6; D000077209:Decitabine; D001374:Azacitidine