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Updated: May 24, 2025

Continuous Fluorescence-Based Endonuclease-Coupled DNA Methylation Assay to Screen for DNA Methyltransferase Inhibitors
Published on: August 5, 2022
Aberrant DNA methylation as a key modulator of cell death pathways: insights into cancer progression and other
Ambreen Zahoor1, Rafia Khazer2, Insha Mehraj1
1Division of Animal Biotechnology, Faculty of Veterinary Sciences & Animal Husbandry, SKUAST-K, Srinagar, 190006, J&K, India.
Abstract:
Cell death plays a significant role in the physiology of all living organisms, and its disruption is the underlying cause of various diseases. Previously, it was assumed that apoptosis and necrosis were the only means of cell death. Recent discoveries of alternative cell death pathways highlighted a complicated interplay between cell death regulation and its role in numerous human pathologies. DNA methylation is a universal epigenetic mechanism characterized by the covalent addition of a methyl group to cytosine in CpG dinucleotides. Alterations in DNA methylation patterns lead to the dysregulation of multiple cell death pathways. DNA methylome studies on cell death pathways have improved our understanding of the mechanism of various types of cell death, such as apoptosis, pyroptosis, necroptosis, ferroptosis, anoikis, autophagy, and cuproptosis. The irregular DNA methylation patterns of genes encoding proteins linked to multiple cell death pathways could underlie resistance to cell death. Dysregulation of cell death is linked to ailments in humans, such as cancer. However, unlike genetic alterations, DNA methylation is reversible, making it extremely interesting for therapeutics considering the potential use of DNA methyltransferase inhibitors. Furthermore, tumor microenvironment and genetic heterogeneity of cancers may influence the methylation-dependent regulation of cell death, contributing to tumor progression and therapeutic resistance. Understanding how DNA methylation influences cell death pathways may illuminate the underlying causes of cancer. This review explores the significance of the DNA methylation patterns of key genes involved in cell death pathways, emphasizing their connections and identifying potential gaps that could be exploited for developing epigenetic therapies targeting cancer.
Insights
DNA methylation patterns critically regulate diverse cell death pathways, including apoptosis and pyroptosis. Aberrant DNA methylation in cancer contributes to disease progression and therapeutic resistance, offering potential epigenetic treatment targets.
Area of Science:
- Epigenetics
- Molecular Biology
- Cancer Biology
Background:
- Cell death is crucial for organismal physiology; its dysregulation underlies many diseases.
- Apoptosis and necrosis were once considered the sole cell death types, but new pathways have been discovered.
- DNA methylation, an epigenetic mechanism, influences gene expression and is implicated in various pathologies.
Purpose of the Study:
- To review the role of DNA methylation in regulating diverse cell death pathways.
- To explore how altered DNA methylation contributes to diseases like cancer.
- To identify potential epigenetic therapeutic strategies targeting cancer.
Main Methods:
- Review of existing literature on DNA methylation and cell death.
- Analysis of DNA methylome studies across various cell death modalities (apoptosis, pyroptosis, necroptosis, ferroptosis, anoikis, autophagy, cuproptosis).
- Examination of the link between DNA methylation patterns and cancer development, progression, and therapeutic resistance.
Main Results:
- Irregular DNA methylation of genes involved in cell death pathways can lead to cell death resistance.
- Dysregulated cell death, influenced by DNA methylation, is a hallmark of cancer.
- DNA methylation is reversible, presenting opportunities for epigenetic therapies, such as DNA methyltransferase inhibitors.
Conclusions:
- DNA methylation patterns significantly impact multiple cell death pathways.
- Understanding these epigenetic modifications is key to elucidating cancer's underlying mechanisms.
- Targeting DNA methylation offers a promising avenue for developing novel cancer therapies.
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