Preprint Review Version 1 This version is not peer-reviewed

Aberrant DNA Methylation in Cholangiocarcinoma

Version 1 : Received: 16 May 2017 / Approved: 16 May 2017 / Online: 16 May 2017 (18:08:59 CEST)

A peer-reviewed article of this Preprint also exists.

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. 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.

Journal reference: Int. J. Mol. Sci. 2017, 18, 1111
DOI: 10.3390/ijms18061111

Abstract

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, 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 diagnosis and treatment of cholangiocarcinoma. Epigenetic therapy with DNA methylation inhibitors hold considerable promise for the treatment of cholangiocarcinoma through re-activation of tumor suppressor genes and miRNAs as well as induction of an anti-viral immune response.

Subject Areas

Cholangiocarcinoma; DNA methylation; Tumor suppressor gene; microRNA; DNA methylation inhibitor

Readers' Comments and Ratings (0)

Leave a public comment
Send a private comment to the author(s)
Rate this article
Views 0
Downloads 0
Comments 0
Metrics 0
Leave a public comment

×
Alerts
Notify me about updates to this article or when a peer-reviewed version is published.