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Telomere Length and Telomerase Activity; A Yin and Yang of Cell Senescence
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Telomerase Regulation: A Role for Epigenetics.

Fatma Dogan1, Nicholas R Forsyth1,2

  • 1The Guy Hilton Research Laboratories, School of Pharmacy and Bioengineering, Faculty of Medicine and Health Sciences, Keele University, Stoke on Trent ST4 7QB, UK.

Cancers
|April 3, 2021
PubMed
Summary

Epigenetic factors, such as DNA methylation and histone modification, are key regulators of telomerase (TERT) expression. Understanding these mechanisms is crucial for cancer treatment and diagnosis.

Keywords:
TERTcancerepigeneticsmethylationpromotertelomerase

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Area of Science:

  • Molecular Biology
  • Epigenetics
  • Cancer Biology

Background:

  • Telomerase, discovered in 1984, plays a critical role in telomere maintenance and influences various cellular processes including cancer.
  • TERT encodes the catalytic subunit of telomerase, and its regulation is complex and not fully understood.
  • Dysregulated TERT expression is implicated in tumorigenesis and therapeutic resistance.

Purpose of the Study:

  • To review the role of epigenetics in regulating telomerase (TERT) activity.
  • To highlight the impact of epigenetic modifications on TERT expression in both normal and cancer cells.
  • To explore the therapeutic and diagnostic potential of understanding epigenetic telomere regulation.

Main Methods:

  • This review synthesizes existing literature on telomerase regulation.
  • It focuses on epigenetic mechanisms including DNA methylation, histone modification, and non-coding RNAs.
  • Analysis of previous studies on TERT promoter mutations and methylation in cancer cell lines.

Main Results:

  • Epigenetic alterations, particularly TERT promoter methylation (53%) and mutations (31%), are frequently observed in TERT-expressing cancer cell lines.
  • Epigenetic regulators are emerging as critical drivers of telomere and telomerase activity.
  • Epigenetic regulation offers a mechanism for reversible TERT silencing in development and increased expression in cancer.

Conclusions:

  • Epigenetic mechanisms are central to the regulation of telomerase (TERT) activity.
  • Understanding these epigenetic controls is vital for developing novel cancer diagnostics and therapeutics.
  • Targeting epigenetic regulators of TERT may offer new avenues for cancer treatment.