Epigenetic Instability Caused by Oxidative Stress Triggers Tumorigenesis
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Date
2022-01-31T00:00:00
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Springer Nature
Abstract
Cancer is a multifactorial disease that is caused by various modifiable as well as non-modifiable factors. Among non-modifiable factors, genetic and epigenetic factors have been reported to play a critical role in the progression of cancer. Epigenetics refers to the change in gene expression without any change in the genome. The major epigenome targets include modification of histones by either methylation or acetylation and methylation of DNA at CpG islands. Change in acetylation and methylation pattern leads to not only inhibition of tumor suppressor genes but also the activation of oncogenes. Oxidative stress is a significant phenomenon observed in human body as a result of various intracellular as well as extracellular factors. This stress interferes with the function of histone methyltransferases and histone deacetylases, resulting in modifications of the epigenome. Further, these oxidative stress-induced epigenetic modifications may occur at various regions, including the promoters of tumor suppressor genes. These result in silencing of genes, leading to increased cell proliferation. In addition, reactive oxygen species have also been found to be involved in regulating the various steps of tumor development, including transformation, survival, proliferation, invasion, metastasis, and angiogenesis. Therefore, oxidative stress can be used as a target for developing cancer-related treatment modalities that reduce oxidative stress levels and thereby help in the resumption of the normal activity of epigenetic enzymes preserving epigenetic integrity. � Springer Nature Singapore Pte Ltd. 2022.
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Keywords
Epigenetic instability, Global hypomethylation, Oxidative stress, Regional hypermethylation, Tumorigenesis