Aberrant DNA methylation as a biomarker and a therapeutic target of cholangiocarcinoma

Toshiaki Nakaoka, Yoshimasa Saito, Hidetsugu Saito

Research output: Contribution to journalReview article

9 Citations (Scopus)

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, 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.

Original languageEnglish
Article number1111
JournalInternational Journal of Molecular Sciences
Volume18
Issue number6
DOIs
Publication statusPublished - 2017 Jun 1

Fingerprint

tumor suppressor genes
methylation
Cholangiocarcinoma
biomarkers
Biomarkers
DNA Methylation
Tumors
deoxyribonucleic acid
Tumor Suppressor Genes
MicroRNAs
Genes
ducts
inhibitors
Ducts
Therapeutics
Death-Associated Protein Kinases
prognosis
Histone Code
chemotherapy
Chemotherapy

Keywords

  • Anti-viral immune response
  • Cholangiocarcinoma
  • DNA methylation
  • Endogenous retrovirus
  • MicroRNA
  • Tumor suppressor gene

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Computer Science Applications
  • Spectroscopy
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

Cite this

Aberrant DNA methylation as a biomarker and a therapeutic target of cholangiocarcinoma. / Nakaoka, Toshiaki; Saito, Yoshimasa; Saito, Hidetsugu.

In: International Journal of Molecular Sciences, Vol. 18, No. 6, 1111, 01.06.2017.

Research output: Contribution to journalReview article

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