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Published on: October 19, 2018
Drugging the R-loop interactome: RNA-DNA hybrid binding proteins as targets for cancer therapy
Beáta Boros-Oláh1, Nikoletta Dobos2, Lilla Hornyák1
1MTA-DE Momentum, Genome Architecture and Recombination Research Group, Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
Abstract:
Unravelling the origin of genetic alterations from point mutations to chromosomal rearrangements was greatly enhanced by the discovery of RNA-DNA hybrids (R-loops) that behave as hotspots of genomic instability in a variety of organisms. Current models suggest that uncontrolled R-loops are a hazard to genome integrity, therefore, identifying proteins that are involved in recognising and signalling R-loop structures are of key importance. Herein we analysed key RNA-DNA hybrid binding proteins in humans taking advantage of large-scale gene expression, survival rate, and drug-sensitivity data from cancer genomics databases. We show that expression of RNA-DNA hybrid binding proteins in various cancer types is associated with survival and may have contrasting outcomes in responding to therapeutic treatments. Based on the revealed pharmacogenomic landscape of human RNA-DNA hybrid binding proteins, we propose that R-loops and R-loop binding proteins are potentially relevant new epigenetic markers and therapeutic targets in multiple cancers.
Insights
RNA-DNA hybrids (R-loops) are linked to genomic instability. Identifying R-loop binding proteins is crucial, as their expression impacts cancer survival and treatment response, suggesting new therapeutic targets.
Area of Science:
- Genomics
- Molecular Biology
- Cancer Research
Background:
- RNA-DNA hybrids (R-loops) are implicated as hotspots for genomic instability, contributing to various genetic alterations.
- Uncontrolled R-loops pose a threat to genome integrity, necessitating the identification of proteins that recognize and signal these structures.
Purpose of the Study:
- To analyze key RNA-DNA hybrid binding proteins in humans.
- To investigate the association of these proteins with cancer patient survival and drug sensitivity using large-scale genomic data.
Main Methods:
- Utilized cancer genomics databases for large-scale gene expression analysis.
- Integrated survival rate and drug-sensitivity data to assess the clinical relevance of RNA-DNA hybrid binding proteins.
Main Results:
- Expression levels of RNA-DNA hybrid binding proteins correlate with patient survival across various cancer types.
- These proteins exhibit contrasting effects on therapeutic treatment outcomes.
Conclusions:
- RNA-DNA hybrid binding proteins show a significant pharmacogenomic landscape in human cancers.
- R-loops and their binding proteins represent potential novel epigenetic markers and therapeutic targets for multiple cancers.
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