DNA and Histone Methylation in Liver Cancer

Eri Arai, Takuya Yotani, Yae Kanai

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

Epigenetic alterations, such as alterations of histone modification and DNA methylation, occur in a genome-wide manner under precancerous conditions resulting from hepatitis B virus (HBV) or hepatitis C virus (HCV) infection followed by chronic hepatitis and cirrhosis, or aberrant lipogenesis and abnormal metabolism of reactive oxygen species that characterize the pathophysiology of non-alcoholic steatohepatitis (NASH). Once DNA methylation alterations occur at the precancerous stage, they are stably preserved on DNA double strands through methylation maintenance by DNA methyltransferase 1 (DNMT1). DNA methylation alterations associated with abnormalities of DNA methyltransferase, such as overexpression of DNMT1 and splicing alterations of DNMT3B, participate in multistage hepatocarcinogenesis from the precancerous stage to the malignant progression stage and are correlated with aggressiveness of hepatocellular carcinomas (HCCs) and poorer outcome of affected patients. A number of tumor-related genes, such as ATK3, APC, BMP4, CCL20, CDH1, CDKN2A, CDKN2B, CSPG2, DAB2IP, DCC, DLC1, DPT, DPYSL3, EMILIN2, FZD7, GRASP, GSTP1, HIST1H4F, IGFALS, MGMT, MZB1, NAT2, NEFH, NFATC1, PAX4, PDSS2, PER3, PROZ, PYCARD, RASSF1A, SPDY1, RUNX3, SCGB1D1, SFN, SMPD3, SOCS1, TIMP3, TLX3, TM6SF1, TRIM33, TRIM58, WFDC6, WNK2 and ZFP41, are known to be silenced by DNA hypermethylation in human HCCs. It is believed that DNA methylation alterations could be excellent biomarkers for carcinogenetic risk estimation and prognostication. To facilitate clinical application of DNA methylation diagnosis, a scaled-down device that allows quick and accurate analysis, even in small hospitals and clinics, is now being developed. One therapeutic strategy against HCC proliferation could involve a combination of epigenetic modifiers, such as a DNA methylation inhibitor, a histone deacetylase inhibitor and an S-adenosylhomocysteine hydrolase inhibitor, to sensitize cancer cells to conventional chemotherapies, in addition to eradication of hepatitis viruses for personalized and/or pre-emptive medical care.

Original languageEnglish
Title of host publicationCancer Drug Discovery and Development
PublisherHumana Press Inc.
Pages437-460
Number of pages24
Edition9783319597843
DOIs
Publication statusPublished - 2017

Publication series

NameCancer Drug Discovery and Development
Number9783319597843
Volume0
ISSN (Print)2196-9906
ISSN (Electronic)2196-9914

Keywords

  • DNA methylation
  • DNMT1
  • DNMT3B
  • Hepatitis virus infection
  • Histone modification
  • Non-alcoholic steatohepatitis
  • Precancerous condition
  • Prognostication
  • Risk estimation

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Drug Discovery

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  • Cite this

    Arai, E., Yotani, T., & Kanai, Y. (2017). DNA and Histone Methylation in Liver Cancer. In Cancer Drug Discovery and Development (9783319597843 ed., pp. 437-460). (Cancer Drug Discovery and Development; Vol. 0, No. 9783319597843). Humana Press Inc.. https://doi.org/10.1007/978-3-319-59786-7_16