title: Promoter methylation of SFRP3 is frequent in hepatocellular carcinoma.
abstract: Oncogenic activation of the Wnt/ β -catenin signaling pathway is common in human cancers. The secreted frizzled-related proteins (SFRPs) function as negative regulators of Wnt signaling and have important implications in carcinogenesis. Because there have been no reports about the role of SFRP3 in hepatocellular carcinoma (HCC), we investigated the level of methylation and transcription of SFRP3. Four HCC cell lines, 60 HCCs, 23 cirrhosis livers, 37 chronic hepatitis livers, and 30 control livers were prescreened for SFRP3 promoter methylation by methylation-specific polymerase chain reaction (MS-PCR) and bisulfite sequencing. SFRP3 promoter methylation was observed in 100%, 60%, 39.1%, 16.2%, and 0% in HCC cell lines, primary HCCs, cirrhosis livers, chronic hepatitis livers, and control livers, respectively. Demethylation treatment with 5-aza-2'-deoxycytidine in HCC cells restored or increased the SFRP3 mRNA expression. We next used quantitative MS-PCR (QMSP) to analyze the methylation level of SFRP3 in 60 HCCs and their corresponding nontumor tissues. Methylation of SFRP3 promoter region in HCCs increased significantly compared with control tissues. There is a positive correlation between promoter hypermethylation and SFRP3 mRNA downregulation. Our data suggest that promoter hypermethylation of SFRP3 is a common event in HCCs and plays an important role in regulation of SFRP3 mRNA expression.
authors.affiliation: Department and Graduate Institute of Microbiology and Immunology, National Defense Medical Center, Taipei, Taiwan ; Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Ya-Wen
authors.identifier: 0000-0002-1639-7941
authors.initials: YW
authors.lastname: Lin
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Yu-Lueng
authors.initials: YL
authors.lastname: Shih
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan.
authors.forename: Gi-Shih
authors.initials: GS
authors.lastname: Lien
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan.
authors.forename: Fat-Moon
authors.initials: FM
authors.lastname: Suk
authors.affiliation: Division of General Surgery, Department of Surgery, National Defense Medical Center, Tri-Service General Hospital, Taipei, Taiwan.
authors.forename: Chung-Bao
authors.initials: CB
authors.lastname: Hsieh
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan.
authors.forename: Ming-De
authors.initials: MD
authors.lastname: Yan
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000235:genetics*; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D019175:DNA Methylation; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D006023:Glycoproteins / Q000235:genetics*; D006391:Hemangioma / Q000235:genetics; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008113:Liver Neoplasms / Q000235:genetics*; D011401:Promoter Regions, Genetic; D000099274:Frizzled-Related Proteins
chemical_list: D006023:Glycoproteins; D047908:Intracellular Signaling Peptides and Proteins; D000099274:Frizzled-Related Proteins