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Alterations of epigenetics and microRNA in hepatocellular carcinoma

Yoshimasa Saito1, Sana Hibino, Hidetsugu Saito

  • 1Division of Pharmacotherapeutics, Faculty of Pharmacy, Keio University, Tokyo, Japan; Division of Gastroenterology and Hepatology, Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan.

Hepatology Research : the Official Journal of the Japan Society of Hepatology
|April 27, 2013
PubMed

Insights

Epigenetic alterations and microRNA (miRNA) dysregulation are key in hepatocellular carcinoma (HCC) development. Targeting these pathways with chromatin-modifying drugs offers a promising therapeutic strategy for HCC.

Area of Science:

  • Oncology
  • Epigenetics
  • Molecular Biology

Background:

  • Epigenetic modifications, including DNA methylation and histone alterations, are crucial in hepatocellular carcinoma (HCC) initiation and progression.
  • MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression and are often aberrantly expressed in HCC, acting as either tumor suppressors or oncogenes.
  • Epigenetic silencing of tumor suppressor miRNAs contributes to hepatocarcinogenesis by activating target oncogenes.

Purpose of the Study:

  • To investigate the roles of epigenetic alterations and microRNA (miRNA) in hepatocellular carcinoma (HCC).
  • To explore the therapeutic potential of targeting epigenetic modifications for HCC treatment.

Main Methods:

  • Review of studies on epigenetic mechanisms (DNA hypermethylation, histone modifications) in HCC.
  • Analysis of the aberrant expression and function of microRNAs (miRNAs) in hepatocarcinogenesis.
  • Evaluation of chromatin-modifying drugs, such as DNA methylation and histone deacetylase inhibitors, in preclinical and clinical settings.

Main Results:

  • Epigenetic silencing, through DNA hypermethylation and histone modifications (H3K9, H3K27), inactivates tumor suppressor genes in HCC.
  • Tumor suppressor miRNAs are frequently silenced by epigenetic alterations in HCC, leading to oncogene activation.
  • Chromatin-modifying drugs show promise in reversing epigenetic silencing and restoring tumor suppressor miRNA expression.

Conclusions:

  • Epigenetic dysregulation and microRNA (miRNA) alterations are central to hepatocellular carcinoma (HCC) pathogenesis.
  • Restoring tumor suppressor miRNA expression via DNA methylation and histone deacetylase inhibitors presents a viable therapeutic strategy for HCC.
Keywords:
DNA methylationepigeneticshepatocellular carcinomahistone modificationmiRNA

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