RNA methylation and cellular response to oxidative stress-promoting anticancer agents
Marco Ponzetti1, Nadia Rucci1, Stefano Falone2
1Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy.
Abstract:
Disruption of the complex network that regulates redox homeostasis often underlies resistant phenotypes, which hinder effective and long-lasting cancer eradication. In addition, the RNA methylome-dependent control of gene expression also critically affects traits of cellular resistance to anti-cancer agents. However, few investigations aimed at establishing whether the epitranscriptome-directed adaptations underlying acquired and/or innate resistance traits in cancer could be implemented through the involvement of redox-dependent or -responsive signaling pathways. This is unexpected mainly because: i) the effectiveness of many anti-cancer approaches relies on their capacity to promote oxidative stress (OS); ii) altered redox milieu and reprogramming of mitochondrial function have been acknowledged as critical mediators of the RNA methylome-mediated response to OS. Here we summarize the current state of understanding on this topic, as well as we offer new perspectives that might lead to original approaches and strategies to delay or prevent the problem of refractory cancer and tumor recurrence.
Insights
Cancer cells develop resistance through altered redox homeostasis and RNA modifications. This review explores the link between these pathways, offering new strategies to combat refractory cancers and prevent recurrence.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Redox homeostasis disruption drives cancer resistance, hindering eradication.
- RNA methylome controls gene expression and cellular resistance to anti-cancer drugs.
- The interplay between epitranscriptome, redox signaling, and cancer resistance remains underexplored.
Purpose of the Study:
- To review the current understanding of epitranscriptome-directed adaptations in cancer resistance.
- To investigate the involvement of redox-dependent pathways in RNA methylome-mediated resistance.
- To propose novel strategies to overcome refractory cancer and tumor recurrence.
Main Methods:
- Literature review and synthesis of existing research.
- Analysis of the role of oxidative stress in cancer resistance.
- Exploration of RNA methylation and redox signaling interactions.
Main Results:
- Oxidative stress is crucial for many anti-cancer therapies.
- Mitochondrial function and redox balance are key in RNA methylome responses to oxidative stress.
- A significant gap exists in understanding the integration of these pathways in cancer resistance.
Conclusions:
- The connection between the epitranscriptome and redox signaling is critical for cancer resistance.
- Understanding this interplay can lead to new therapeutic strategies.
- Targeting these pathways may prevent refractory cancer and tumor recurrence.
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