2. Academic Validation
  3. The role and prospect of lysine-specific demethylases in cancer chemoresistance

The role and prospect of lysine-specific demethylases in cancer chemoresistance

  • Med Res Rev. 2023 Apr 3. doi: 10.1002/med.21955.
Ying-Qi Song 1,  Guan-Jun Yang 1 2 3,  Dik-Lung Ma 4,  Wanhe Wang 5,  Chung-Hang Leung 1 6
Affiliations

Affiliations

  • 1 State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China.
  • 2 State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products, Ningbo University, Ningbo, Zhejiang, China.
  • 3 Laboratory of Biochemistry and Molecular Biology, School of Marine Sciences, Ningbo University, Ningbo, Zhejiang, China.
  • 4 Department of Chemistry, Hong Kong Baptist University, Hong Kong, China.
  • 5 Institute of Medical Research, Northwestern Polytechnical University, Xi'an, Shaanxi, China.
  • 6 Department of Biomedical Sciences, Faculty of Health Sciences, University of Macau, Macao, China.
PMID: 37012609 DOI: 10.1002/med.21955
Abstract

Histone methylation plays a key function in modulating gene expression, and preserving genome integrity and epigenetic inheritance. However, aberrations of histone methylation are commonly observed in human diseases, especially Cancer. Lysine methylation mediated by histone methyltransferases can be reversed by lysine demethylases (KDMs), which remove methyl marks from histone lysine residues. Currently, drug resistance is a main impediment for Cancer therapy. KDMs have been found to mediate drug tolerance of many cancers via altering the metabolic profile of Cancer cells, upregulating the ratio of Cancer Stem Cells and drug-tolerant genes, and promoting the epithelial-mesenchymal transition and metastatic ability. Moreover, different cancers show distinct oncogenic addictions for KDMs. The abnormal activation or overexpression of KDMs can alter gene expression signatures to enhance cell survival and drug resistance in Cancer cells. In this review, we describe the structural features and functions of KDMs, the KDMs preferences of different cancers, and the mechanisms of drug resistance resulting from KDMs. We then survey KDM inhibitors that have been used for combating drug resistance in Cancer, and discuss the opportunities and challenges of KDMs as therapeutic targets for Cancer Drug Resistance.

Keywords

cancer; drug resistance; epigenetics; inhibitor; lysine-specific demethylases.

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