Title:Histone Lysine-Specific Methyltransferases and Demethylases in Carcinogenesis: New Targets for Cancer Therapy and Prevention
Volume: 13
Issue: 5
Author(s): Xuejiao Tian, Saiyang Zhang, Hong-Min Liu, Yan-Bing Zhang, Christopher A. Blair, Dan Mercola, Paolo Sassone-Corsi and Xiaolin Zi
Affiliation:
Keywords:
Carcinogenesis, cell transformation, gene mutations, histone lysine-specific demethylases, histone lysine-specific
methyltransferases, inhibitors.
Abstract: Aberrant histone lysine methylation that is controlled by histone lysine methyltransferases (KMTs) and
demethylases (KDMs) plays significant roles in carcinogenesis. Infections by tumor viruses or parasites and exposures to
chemical carcinogens can modify the process of histone lysine methylation. Many KMTs and KDMs contribute to
malignant transformation by regulating the expression of human telomerase reverse transcriptase (hTERT), forming a
fused gene, interacting with proto-oncogenes or being up-regulated in cancer cells. In addition, histone lysine methylation
participates in tumor suppressor gene inactivation during the early stages of carcinogenesis by regulating DNA
methylation and/or by other DNA methylation independent mechanisms. Furthermore, recent genetic discoveries of many
mutations in KMTs and KDMs in various types of cancers highlight their numerous roles in carcinogenesis and provide
rare opportunities for selective and tumor-specific targeting of these enzymes. The study on global histone lysine
methylation levels may also offer specific biomarkers for cancer detection, diagnosis and prognosis, as well as for
genotoxic and non-genotoxic carcinogenic exposures and risk assessment. This review summarizes the role of histone
lysine methylation in the process of cellular transformation and carcinogenesis, genetic alterations of KMTs and KDMs in
different cancers and recent progress in discovery of small molecule inhibitors of these enzymes.
