China
Africa
Explore chapters and articles related to this topic
Introduction to Cancer
Published in Anjana Pandey, Saumya Srivastava, Recent Advances in Cancer Diagnostics and Therapy, 2022
Anjana Pandey, Saumya Srivastava
Deacetylation is another condition, which is found in different tumors, catalyzed by histone deacetylases (HDAC). Regulation of HDACs expression was found to be regulated by microRNAs: for example, in prostate cancer, cell growth and survival are regulated by miR-449a via inhibition of HDAC1 expression. Besides the changes in HDAC expression in different types of cancer like colon, lung, and leukemia, disruption in histone acetylation occurs also via deletion and ectopic mutations in HAT (Histone acetyltransferase) and associated genes. These all conditions lead to tumor formation (Noonan et al., 2009; Yen et al., 2016; Sato et al., 2017; Spencer et al., 2017; Quintela et al., 2019; Dai et al., 2021; Hogg et al., 2021). Histone methylation alterations occur mainly due to histone methyltransferases and demethylase expressions. In the case of leukemia, H3K4 (Histone3 lysine4) and H3K29 abnormal methylation patterns are observed due to MLL oncoprotein. This leads to altered expressions of MLL target genes (Wang et al., 2009). ATPase subunits (BRG1 and BRM), associated with SWI/SNF complex, are known tumor suppressors and found to be responsible for 15–20% lung cancer cases. SWI/SNF complex is found to be involved in the generation of different types of cancer by interacting with the retinoblastoma protein gene, p53, MYC, and BRCA1. Hence, the dysfunctional SWI/SNF complex leads to a disturbance in cell growth (Mohd-Sarip et al., 2017; Pierre and Kadoch, 2017; Szymanski et al., 2017; Yoshimoto, Matsubara and Niki, 2017; Agaimy et al., 2018; Alpsoy and Dykhuizen, 2018; Moreno et al., 2018; Savas and Skardasi, 2018; Sinha et al., 2018).
Epigenetic and Metabolic Alterations in Cancer Cells: Mechanisms and Therapeutic Approaches
Published in Peter Grunwald, Pharmaceutical Biocatalysis, 2020
Aberrant histone acetylation has been consistently associated with tumorigenesis. Histone acetylation diminishes the electrostatic repulsion between DNA and histones, leading to an open chromatin structure permissive for gene transcription (Grunstein, 1997). Histone acetylation is regulated by the opposing actions of histone acetyltransferases (HATs) and deacetylases (HDACs). Overexpression of HDACs, in particular, has been detected in multiple cancers (Glozak and Seto, 2007). HDACs are thought to promote histone deacetylation and transcriptionally repress the expression of tumor suppressor genes (Kim et al., 2001; Zhang et al., 2003). Key tumor suppressor genes, including p21WAF1, E-cadherin, and others, have been shown to be silenced by HDACs in cancers (Aghdassi et al., 2012; Wilson et al., 2006). Apart from acetylation, histone methylation is another histone modification that has an impact on gene expression. Up to 19 lysine residues on Histone H3 can be methylated, and each of these lysine residues can be mono-, di-, or tri-methylated, thus giving rise to a highly complex histone code (Greer and Shi, 2012). Histone methylation is also tightly regulated through the action of methyltransferases and demethylases. Much remains to be understood with regard to the effect of aberrant histone methylation on cancer development, but it is clear that this will be methylation site-specific and context dependent. A well-known example is the H3K79 histone methyltransferase DOT1-like (DOT1L) protein, whose mistargeting triggers aberrant H3K79 methylation at homeobox genes in MLL re-arranged leukemia (Bernt et al., 2011; Onder et al., 2012). Therapeutic agents targeting histone acetylation or methylation have been under active development. HDAC inhibitors (HDACi) have been put forward for cancer therapy, based on the premise that HDACi might reverse HDAC-mediated repression of tumor suppressor genes. HDACi such as Vorinostat and Romidepsin have been approved for the treatment of cutaneous T cell lymphoma (CTCL) and HDACi are undergoing Phase II/III clinical trials for CTCL, and solid tumors (Moskowitz and Horwitz, 2017). Drugs targeting DOT1L (Pinometostat, EPZ-5676) have been described, showing dramatic effects in preclinical models of MLL-rearranged leukemia and is currently undergoing phase I/II trials.
Epigenotoxicity: a danger to the future life
Published in Journal of Environmental Science and Health, Part A, 2023
Farzaneh Kefayati, Atoosa Karimi Babaahmadi, Taraneh Mousavi, Mahshid Hodjat, Mohammad Abdollahi
This reaction occurs by increasing the methyl group to arginine and lysine amino acids. The enzyme used for that reaction is methyltransferase, a reversible and continuous reaction since cell division increases this chemical reaction.[15] Demethylase catalyzes and removes methyl groups, contrary to methyltransferase activity. This has the opposite effect on the epigenetic regulation of genes. What remains of lysines can be mono-, di- or tri-methylated. Histone methylation is related to the silencing and activation of gene expression.[16]