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Inhibition of SOX17 by MicroRNA 141 and Methylation Activates the WNT Signaling Pathway in Esophageal Cancer

icecream 添加于 2012-10-14 22:29 | 998 次阅读 | 0 个评论

作者
Jia Y, Yang Y, Zhan Q, Brock MV, Zheng X, Yu Y, Herman JG, Guo M
摘要
In this study, we explored the possibility of SOX17 promoter region methylation as an esophageal cancer detection marker, the regulation of SOX17 expression, and the function of SOX17 in the WNT signaling pathway in esophageal cancer. Eight esophageal cancer cell lines, 9 normal esophageal mucosa samples, 60 cases of dysplasia, and 169 cancer tissue samples were included. Methylation-specific PCR, semiquantitative reverse transcription-PCR, immunohistochemistry, luciferase reporter assay, colony formation, and Western blot analysis were used to analyze methylation and function of SOX17 in esophageal cancer. MicroRNA-related detection methods were performed to evaluate microRNA regulation of SOX17. SOX17 methylation was found in progression tendency with 0% of normal mucosa, 39% of grade 1 dysplasia, 48% of grades 2 and 3 dysplasia, and 65% of primary cancer. SOX17 methylation is related to esophageal cancer patients' history of alcohol use and may induce beta-catenin expression and redistribution. Loss of SOX17 expression is correlated to promoter region hypermethylation, and re-expression was activated by 5-aza-2'-deoxycytidine treatment in esophageal cancer cell lines. Restoration of SOX17 expression suppresses TCF/beta-catenin-dependent transcription and colony formation. MicroRNA 141 was also found to down-regulate SOX17 expression and activate the WNT signal pathway. SOX17 is frequently methylated in esophageal cancer and in a progression tendency during esophageal carcinogenesis. Loss of SOX17 removes the normal inhibition of WNT signaling and promotes esophageal tumorigenesis.
详细资料
- 文献种类: Journal Article
- 期刊名称: The Journal of Molecular Diagnostics : JMD
- 期刊缩写: J Mol Diagn
- 期卷页: 2012年第14卷第6期 577-585页
- 地址: Department of Gastroenterology & Hepatology, Chinese PLA General Hospital, Beijing, China; Medical College of NanKai University, Tianjin, China
- ISBN: 1525-1578
学科领域生物医药 » 预防卫生学
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