Histone Methyltransferases as a New Target for Epigenetic Action of Vorinostat
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Published:2023-07
Issue:7
Volume:88
Page:968-978
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ISSN:0006-2979
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Container-title:Biochemistry (Moscow)
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language:en
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Short-container-title:Biochemistry Moscow
Author:
Maksimova Varvara,Makus Julia,Popova Valeriia,Prus Anzhelika,Usalka Olga,Trapeznikova Ekaterina,Zhidkova Ekaterina,Belitsky Gennady,Yakubovskaya Marianna,Kirsanov Kirill
Abstract
Abstract
Epigenetic genome regulation during malignant cell transformation is characterized by the aberrant methylation and acetylation of histones. Vorinostat (SAHA) is an epigenetic modulator actively used in clinical oncology. The antitumor activity of vorinostat is commonly believed to be associated with the inhibition of histone deacetylases, while the impact of this drug on histone methylation has been poorly studied. Using HeLa TI cells as a test system allowing evaluation of the effect of epigenetically active compounds from the expression of the GFP reporter gene and gene knockdown by small interfering RNAs, we showed that vorinostat not only suppressed HDAC1, but also reduced the activity of EZH2, SUV39H1, SUV39H2, and SUV420H1. The ability of vorinostat to suppress expression of EZH2, SUV39H1/2, SUV420H1 was confirmed by Western blotting. Vorinostat also downregulated expression of SUV420H2 and DOT1L enzymes. The data obtained expand our understanding of the epigenetic effects of vorinostat and demonstrate the need for a large-scale analysis of its activity toward other enzymes involved in the epigenetic genome regulation. Elucidation of the mechanism underlying the epigenetic action of vorinostat will contribute to its more proper use in the treatment of tumors with an aberrant epigenetic profile.
Publisher
Pleiades Publishing Ltd
Subject
Biochemistry,General Medicine,Biochemistry, Genetics and Molecular Biology (miscellaneous),Biophysics,Geriatrics and Gerontology
Reference72 articles.
1. Tian, X., Zhang, S., Liu, H. M., Zhang, Y. B., Blair, C. A., Mercola, D., Sassone-Corsi, P., and Zi, X. (2013) Histone lysine-specific methyltransferases and demethylases in carcinogenesis: new targets for cancer therapy and prevention, Curr. Cancer Drug Targets, 13, 558-579,
https://doi.org/10.2174/1568009611313050007. 2. Zhao, S., Allis, C. D., and Wang, G. G. (2021) The language of chromatin modification in human cancers, Nat. Rev. Cancer, 21, 413-430,
https://doi.org/10.1038/s41568-021-00357-x. 3. Lam, U. T. F., Tan, B. K. Y., Poh, J. J. X., and Chen, E. S. (2022) Structural and functional specificity of H3K36 methylation, Epigenetics Chromatin, 15, 17,
https://doi.org/10.1186/s13072-022-00446-7. 4. Greer, E. L., and Shi, Y. (2012) Histone methylation: a dynamic mark in health, disease and inheritance, Nat. Rev. Genet., 13, 343-357,
https://doi.org/10.1038/nrg3173. 5. Santos-Rosa, H., Schneider, R., Bannister, A. J., Sherriff, J., Bernstein, B. E., Emre, N. C., Schreiber, S. L., Mellor, J., and Kouzarides, T. (2002) Active genes are tri-methylated at K4 of histone H3, Nature, 419, 407-411,
https://doi.org/10.1038/nature01080.
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