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.

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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