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Int. J. Mol. Sci. 2017, 18(6), 1111; doi:10.3390/ijms18061111

Aberrant DNA Methylation as a Biomarker and a Therapeutic Target of Cholangiocarcinoma

Division of Pharmacotherapeutics, Keio University Faculty of Pharmacy, 1-5-30 Shibakoen, Minato-ku, Tokyo 105-8512, Japan
Author to whom correspondence should be addressed.
Academic Editor: Nicoletta Sacchi
Received: 17 April 2017 / Revised: 16 May 2017 / Accepted: 18 May 2017 / Published: 23 May 2017
(This article belongs to the Special Issue Cancer Epigenetics)
View Full-Text   |   Download PDF [660 KB, uploaded 23 May 2017]   |  


Cholangiocarcinoma is an epithelial malignancy arising in the region between the intrahepatic bile ducts and the ampulla of Vater at the distal end of the common bile duct. The effect of current chemotherapy regimens against cholangiocarcinoma is limited, and the prognosis of patients with cholangiocarcinoma is poor. Aberrant DNA methylation and histone modification induce silencing of tumor suppressor genes and chromosomal instability during carcinogenesis. Studies have shown that the tumor suppressor genes and microRNAs (miRNAs) including MLH1, p14, p16, death-associated protein kinase (DAPK), miR-370 and miR-376c are frequently methylated in cholangiocarcinoma. Silencing of these tumor suppressor genes and miRNAs plays critical roles in the initiation and progression of cholangiocarcinoma. In addition, recent studies have demonstrated that DNA methylation inhibitors induce expression of endogenous retroviruses and exert the anti-tumor effect of via an anti-viral immune response. Aberrant DNA methylation of tumor suppressor genes and miRNAs could be a powerful biomarker for the diagnosis and treatment of cholangiocarcinoma. Epigenetic therapy with DNA methylation inhibitors holds considerable promise for the treatment of cholangiocarcinoma through the reactivation of tumor suppressor genes and miRNAs as well as the induction of an anti-viral immune response. View Full-Text
Keywords: cholangiocarcinoma; DNA methylation; tumor suppressor gene; microRNA; endogenous retrovirus; anti-viral immune response cholangiocarcinoma; DNA methylation; tumor suppressor gene; microRNA; endogenous retrovirus; anti-viral immune response

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Nakaoka, T.; Saito, Y.; Saito, H. Aberrant DNA Methylation as a Biomarker and a Therapeutic Target of Cholangiocarcinoma. Int. J. Mol. Sci. 2017, 18, 1111.

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