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Emerging role of mRNA epitranscriptomic regulation in chemoresistant cancer cells

Shensi Shen1, Xiaoxiao Sun2

  • 1Inserm U981, Gustave Roussy Cancer Campus, Villejuif, France.

Molecular & Cellular Oncology
|May 12, 2020
PubMed

Insights

Cancer persister cells can be overcome by targeting mRNA translation. Melanoma cells reprogram translation via N6-methyladenosine modification, which can be blocked by targeting eIF4A to prevent resistance.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Cancer persister cells pose a significant challenge to current anti-cancer therapies.
  • Understanding the mechanisms of persister cell survival is crucial for developing more effective treatments.

Purpose of the Study:

  • To investigate the molecular mechanisms underlying the survival of melanoma persister cells.
  • To identify potential therapeutic targets to overcome treatment resistance.

Main Methods:

  • Analysis of mRNA translation reprogramming in melanoma persister cells.
  • Investigating the role of N6-methyladenosine (m6A) modification in 5'-untranslated regions of mRNAs.
  • Assessing the impact of targeting eukaryotic initiation factor 4A (eIF4A) on persister cell emergence.

Main Results:

  • Melanoma persister cells exhibit a reversible reprogramming of mRNA translation.
  • A subset of mRNAs with m6A in their 5'-untranslated regions shows increased translation.
  • Upregulation of translation is dependent on eIF4A activity.

Conclusions:

  • Targeting eIF4A can prevent the emergence of drug-resistant melanoma clones.
  • Modulation of mRNA translation and m6A modification represents a promising strategy against cancer persister cells.
Keywords:
Cancer persister cellepitranscriptomicmRNA translation

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