Promoter methylation of SFRP3 is frequent in hepatocellular carcinoma

Ya Wen Lin, Yu Lueng Shih, Gi Shih Lien, Fat Moon Suk, Chung Bao Hsieh, Ming De Yan

Research output: Contribution to journalArticle

10 Citations (Scopus)

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.

Original languageEnglish
Article number351863
JournalDisease Markers
Volume2014
DOIs
Publication statusPublished - 2014

Fingerprint

Methylation
Hepatocellular Carcinoma
Liver
Polymerase chain reaction
decitabine
Chronic Hepatitis
Liver Cirrhosis
Messenger RNA
Cells
Tissue
Cell Line
Catenins
Polymerase Chain Reaction
Wnt Signaling Pathway
Transcription
Genetic Promoter Regions
Carcinogenesis
Down-Regulation
Chemical activation

ASJC Scopus subject areas

  • Biochemistry, medical
  • Clinical Biochemistry
  • Molecular Biology
  • Genetics
  • Medicine(all)

Cite this

Promoter methylation of SFRP3 is frequent in hepatocellular carcinoma. / Lin, Ya Wen; Shih, Yu Lueng; Lien, Gi Shih; Suk, Fat Moon; Hsieh, Chung Bao; Yan, Ming De.

In: Disease Markers, Vol. 2014, 351863, 2014.

Research output: Contribution to journalArticle

Lin, Ya Wen ; Shih, Yu Lueng ; Lien, Gi Shih ; Suk, Fat Moon ; Hsieh, Chung Bao ; Yan, Ming De. / Promoter methylation of SFRP3 is frequent in hepatocellular carcinoma. In: Disease Markers. 2014 ; Vol. 2014.
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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.",
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