Histone deacetylase‑2: A potential regulator and therapeutic target in liver disease (Review)

Int J Mol Med. 2021 Jul;48(1):131. doi: 10.3892/ijmm.2021.4964. Epub 2021 May 20.

Abstract

Histone acetyltransferases are responsible for histone acetylation, while histone deacetylases (HDACs) counteract histone acetylation. An unbalanced dynamic between histone acetylation and deacetylation may lead to aberrant chromatin landscape and chromosomal function. HDAC2, a member of class I HDAC family, serves a crucial role in the modulation of cell signaling, immune response and gene expression. HDAC2 has emerged as a promising therapeutic target for liver disease by regulating gene transcription, chromatin remodeling, signal transduction and nuclear reprogramming, thus receiving attention from researchers and clinicians. The present review introduces biological information of HDAC2 and its physiological and biochemical functions. Secondly, the functional roles of HDAC2 in liver disease are discussed in terms of hepatocyte apoptosis and proliferation, liver regeneration, hepatocellular carcinoma, liver fibrosis and non‑alcoholic steatohepatitis. Moreover, abnormal expression of HDAC2 may be involved in the pathogenesis of liver disease, and its expression levels and pharmacological activity may represent potential biomarkers of liver disease. Finally, research on selective HDAC2 inhibitors and non‑coding RNAs relevant to HDAC2 expression in liver disease is also reviewed. The aim of the present review was to improve understanding of the multifunctional role and potential regulatory mechanism of HDAC2 in liver disease.

Keywords: histone deacetylase 2; inhibitor; liver disease; non‑coding RNA.

Publication types

  • Review

MeSH terms

  • Acetylation
  • Apoptosis
  • Carcinoma, Hepatocellular / enzymology
  • Carcinoma, Hepatocellular / therapy
  • Cell Proliferation
  • Hepatocytes / enzymology
  • Histone Deacetylase 2 / genetics
  • Histone Deacetylase 2 / metabolism*
  • Histones / metabolism*
  • Humans
  • Liver Cirrhosis / enzymology
  • Liver Cirrhosis / therapy
  • Liver Diseases / enzymology*
  • Liver Diseases / therapy
  • Liver Regeneration
  • Non-alcoholic Fatty Liver Disease / enzymology
  • Non-alcoholic Fatty Liver Disease / therapy
  • RNA, Untranslated / genetics*

Substances

  • Histones
  • RNA, Untranslated
  • HDAC2 protein, human
  • Histone Deacetylase 2

Grants and funding

The present study was supported by the National Natural Science Foundation of China (grant no. 81770609).