Aberrant DNA methylation in hepatocellular carcinoma tumor suppression (Review)

Dong,Youhong; Wang,Anping

doi:10.3892/ol.2014.2301

Aberrant DNA methylation in hepatocellular carcinoma tumor suppression (Review)

Authors:
- Youhong Dong
- Anping Wang
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Affiliations: Oncology Department, Xiangyang Hospital Affiliated to Hubei University of Medicine, Xiangyang, Hubei 441000, P.R. China
Published online on: July 1, 2014 https://doi.org/10.3892/ol.2014.2301
Pages: 963-968

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Abstract

Aberrant DNA methylation leads to altered gene expression, resulting in cancerous features. Numerous tumor suppressor genes are silenced by DNA methylation during hepatocarcinogenesis. Promoter CpG island hypermethylation is an important mechanism for inactivating tumor suppressor genes in hepatocellular carcinoma (HCC). Hypermethylation of CpG islands in the p16 (INK4a) and p15 (INK4b) promoters may increase the risk of developing HCC, particularly hepatitis B virus‑related HCC. Environmental factors can lead to geographic variations in the methylation status of CpG islands. Aberrant DNA methylation of CpG islands is catalyzed by DNA methyltransferases (DNMTs). Thus, abnormal variations of DNMTs can contribute to hepatocarcinogenesis. In hepatitis‑related HCC, microRNAs participate in hepatocarcinogenesis by directly targeting DNMTs, during which hepatitis B virus X acts as a regulator. DNA methylation may also contribute to HCC tumorigenesis by regulating the cell cycle. Based on the importance of DNA methylation in tumor suppression of HCC, certain DNA methylations may predict the risk of tumor development, tumor staging, patient survival and HCC recurrence.

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