Epigenetic mechanisms regulating the development of hepatocellular carcinoma and their promise for therapeutics.
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.
Royal Hobart Hospital Tasmania, Hobart, Australia.
Faisal Saeed
FS
Khan
COMSATS Institute of Information Technology, Islamabad, Pakistan.
Ijaz
I
Ali
Department of Biochemistry, Abdul Wali Khan University Mardan, Mardan, 25200, Pakistan.
Ume Kalsoom
UK
Afridi
Western University, London, ON, Canada.
Muhammad
M
Ishtiaq
Children's Health Research Institute, London Health Sciences Centre, Western University, 800 Commissioners Rd E, Victoria Research Labs, London, ON, Canada. rmehmood@uwo.ca.
Rashid
R
Mehmood
D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000235:genetics*; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy / Q000235:genetics*
D000970:Antineoplastic Agents
Epi-drugs; Epigenetic regulation; HCC; Hepatocarcinogenesis; Therapeutics; Tumor suppressors