The emerging roles of HDACs and their therapeutic implications in cancer

Rihan Hai; Deyi Yang; Feifei Zheng; Weiqin Wang; Xing Han; Ann M Bode; Xiangjian Luo

doi:10.1016/j.ejphar.2022.175216

The emerging roles of HDACs and their therapeutic implications in cancer

Eur J Pharmacol. 2022 Sep 15:931:175216. doi: 10.1016/j.ejphar.2022.175216. Epub 2022 Aug 18.

Authors

Rihan Hai¹, Deyi Yang¹, Feifei Zheng¹, Weiqin Wang¹, Xing Han¹, Ann M Bode², Xiangjian Luo³

Affiliations

¹ Key Laboratory of Carcinogenesis and Invasion, Chinese Ministry of Education, Department of Nuclear Medicine, Xiangya Hospital, Central South University, Changsha, Hunan, 410078, PR China; Cancer Research Institute, School of Basic Medicine, Central South University, Changsha, Hunan, 410078, PR China.
² The Hormel Institute, University of Minnesota, Austin, MN, 55912, USA.
³ Key Laboratory of Carcinogenesis and Invasion, Chinese Ministry of Education, Department of Nuclear Medicine, Xiangya Hospital, Central South University, Changsha, Hunan, 410078, PR China; Cancer Research Institute, School of Basic Medicine, Central South University, Changsha, Hunan, 410078, PR China; Hunan Key Laboratory of Oncotarget Gene, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, 410078, China; Key Laboratory of Biological Nanotechnology of National Health Commission, Central South University, Changsha, Hunan, 410078, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410078, China. Electronic address: luocsu@csu.edu.cn.

PMID: 35988787
DOI: 10.1016/j.ejphar.2022.175216

Abstract

Deregulation of protein post-translational modifications is intensively involved in the etiology of diseases, including degenerative diseases, inflammatory injuries, and cancers. Acetylation is one of the most common post-translational modifications of proteins, and the acetylation levels are controlled by two mutually antagonistic enzyme families, histone acetyl transferases (HATs) and histone deacetylases (HDACs). HATs loosen the chromatin structure by neutralizing the positive charge of lysine residues of histones; whereas HDACs deacetylate certain histones, thus inhibiting gene transcription. Compared with HATs, HDACs have been more intensively studied, particularly regarding their clinical significance. HDACs extensively participate in the regulation of proliferation, migration, angiogenesis, immune escape, and therapeutic resistance of cancer cells, thus emerging as critical targets for clinical cancer therapy. Compared to HATs, inhibitors of HDAC have been clinically used for cancer treatment. Here, we enumerate and integratethe mechanisms of HDAC family members in tumorigenesis and cancer progression, and address the new and exciting therapeutic implications of single or combined HDAC inhibitor (HDACi) treatment.

Keywords: Acetylation; Cancer; Epigenetic modification; HDACis; HDACs.

Publication types

Review

MeSH terms

Acetylation
Histone Deacetylase Inhibitors / pharmacology
Histone Deacetylase Inhibitors / therapeutic use
Histone Deacetylases* / metabolism
Histones / metabolism
Humans
Neoplasms* / drug therapy

Substances

Histone Deacetylase Inhibitors
Histones
Histone Deacetylases