Frequent concomitant epigenetic silencing of SOX1 and secreted frizzled‐related proteins (SFRPs) in human hepatocellular carcinoma. Issue 3 (26th February 2013)

• Record Type: Journal Article
• Authors: Shih, Yu‐Lueng; Hsieh, Chung‐Bao; Yan, Ming‐De; Tsao, Chun‐Ming; Hsieh, Tsai‐Yuan; Liu, Chang‐Hsin; Lin, Ya‐Wen
• Is Part Of: Journal of gastroenterology and hepatology. Volume 28:Issue 3(2013:Mar.)
• Page Start: 551
• Page End: 559
• Publication Date: 2013-02-26
• Subjects: Gastroenterology -- Periodicals; Digestive organs -- Diseases -- Periodicals; Liver -- Diseases -- Periodicals; Gastroenterology -- Periodicals; Liver Diseases -- Periodicals; 616.33
• DOI: 10.1111/jgh.12078
• Languages: English
• ISSNs: 0815-9319

Abstract

<abstract abstract-type="main"> <title>Abstract</title> <sec id="jgh12078-sec-0001" sec-type="section"> <title>Background and Aim</title> <p>Except for genetic mutations, epigenetic changes are also involved in the development of human cancers. Recently, we have identified <italic>SOX1</italic>, SRY (sex determining region Y)‐box 1, is hypermethylated in cervical cancer and ovarian cancer. Therefore, we investigated whether promoter hypermethylation of <italic>SOX1</italic> is common in hepatocellular carcinoma (HCC).</p> </sec> <sec id="jgh12078-sec-0002" sec-type="section"> <title>Methods</title> <p>We used methylation‐specific polymerase chain reaction (MS‐PCR) and bisulfite sequencing to analyze the methyaltion level of the <italic>SOX1</italic> promoter in seven HCC cell lines, 54 clinical HCCs, 42 cirrhotic livers, 21 livers with chronic hepatitis, and 15 control livers. Then, we employed quantitative MS‐PCR (QMSP) to validate in an independent set of samples (60 paired HCCs and 30 control livers). Finally, we used luciferase reporter and colony formation assay to check the effect of SOX1 in HCC.</p> </sec> <sec id="jgh12078-sec-0003" sec-type="section"> <title>Results</title> <p>Promoter methylation of <italic>SOX1</italic> was significantly frequent in HCC cell lines and clinical HCCs, cirrhotic livers, but not in control livers (<italic>P</italic> < 0.0001). There is a significant correlation between downregulation of <italic>SOX1</italic> expression and promoter methylation. QMSP results confirmed that promoter hypermethylation of <italic>SOX1</italic> is significantly more frequent in HCCs than control livers (<italic>P</italic> < 0.0001). The frequency of <italic>SOX1</italic> methylation in patients with secreted frizzled‐related proteins (<italic>SFRP</italic>s) methylation is significantly higher than in patients without <italic>SFRP</italic>s methylation (<italic>P</italic> < 0.0001). Furthermore, ectopic expression of <italic>SOX1</italic> could suppress T‐cell factor‐dependent transcriptional activity and colony formation number in HCCs.</p> </sec> <sec id="jgh12078-sec-0004" sec-type="section"> <title>Conclusions</title> <p>Concomitant epigenetic silencing of <italic>SOX1</italic> and <italic>SFRPs</italic> through promoter hypermethylation is frequent in HCCs, and this might contribute to abnormal activation of canonical Wnt signal pathway.</p> </sec> </abstract>