Hepatology International

, Volume 11, Issue 1, pp 45–53 | Cite as

Epigenetic mechanisms regulating the development of hepatocellular carcinoma and their promise for therapeutics

  • Faisal Saeed Khan
  • Ijaz Ali
  • Ume Kalsoom Afridi
  • Muhammad Ishtiaq
  • Rashid Mehmood
Review Article


Hepatocellular carcinoma (HCC) is one of the most common cancers around the globe and third most fatal malignancy. Chronic liver disorders such as chronic hepatitis and liver cirrhosis often lead to the development of HCC. Accumulation of genetic and epigenetic alterations are involved in the development of HCC. Genetic research sparked by recent developments in next generation sequencing has identified the frequency of genetic alterations that occur in HCC and has led to the identification of genetic hotspots. Emerging evidence suggests that epigenetic aberrations are strongly associated with the initiation and development of HCC. Various important genes encoding tumor suppressors including P16, RASSF1A, DLC-1, RUNX3 and SOCS-1 are targets of epigenetic dysregulation during the development of HCC. The present review discusses the importance of epigenetic regulations including DNA methylation, histone modification and microRNA mediated regulation of gene expression during tumorigenesis and their use as disease biomarkers. Furthermore, these epigenetic alterations have been discussed in relationship with promising therapeutic perspectives for HCC and related cancers.


Hepatocarcinogenesis HCC Epigenetic regulation Therapeutics Epi-drugs Tumor suppressors 



Hepatitis C virus


Hepatocellular carcinoma




Histone deacetylase


Polycomb repressive complex 1


Non structural protein 3


DNA methyltransferases


CpG islands


3-Deazaneplanocin A


Compliance with ethical standards

Conflict of interest

Faisal Saeed Khan, Ijaz Ali, Ume Kalsoom Afridi, Muhammad Ishtiaq and Rashid Mehmood declare that they have no conflict of interest.

Ethical approval

No animals were involved in the study.

Informed consent

No humans were involved in the study.


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Copyright information

© Asian Pacific Association for the Study of the Liver 2016

Authors and Affiliations

  • Faisal Saeed Khan
    • 1
  • Ijaz Ali
    • 2
  • Ume Kalsoom Afridi
    • 3
  • Muhammad Ishtiaq
    • 4
  • Rashid Mehmood
    • 5
  1. 1.Royal Hobart Hospital TasmaniaHobartAustralia
  2. 2.COMSATS Institute of Information TechnologyIslamabadPakistan
  3. 3.Department of BiochemistryAbdul Wali Khan University MardanMardanPakistan
  4. 4.Western UniversityLondonCanada
  5. 5.Children’s Health Research Institute, London Health Sciences CentreWestern UniversityLondonCanada

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