Publication:
A Comprehensive Analysis of the Effect of A>I(G) RNA-Editing Sites on Genotoxic Drug Response and Progression in Breast Cancer

Simple item page
dc.contributor.authorBernal, Yanara
dc.contributor.authorBlanco, Alejandro
dc.contributor.authorSagredo, Eduardo
dc.contributor.authorOróstica, Karen
dc.contributor.authorAlfaro, Ivan
dc.contributor.authorMarcelain, Katherine
dc.contributor.authorArmisén, Ricardo
dc.date.accessioned2024-07-25T15:40:37Z
dc.date.available2024-07-25T15:40:37Z
dc.date.issued2024
dc.description.abstractDysregulated A>I(G) RNA editing, which is mainly catalyzed by ADAR1 and is a type of post-transcriptional modification, has been linked to cancer. A low response to therapy in breast cancer (BC) is a significant contributor to mortality. However, it remains unclear if there is an association between A>I(G) RNA-edited sites and sensitivity to genotoxic drugs. To address this issue, we employed a stringent bioinformatics approach to identify differentially RNA-edited sites (DESs) associated with low or high sensitivity (FDR 0.1, log2 fold change 2.5) according to the IC50 of PARP inhibitors, anthracyclines, and alkylating agents using WGS/RNA-seq data in BC cell lines. We then validated these findings in patients with basal subtype BC. These DESs are mainly located in non-coding regions, but a lesser proportion in coding regions showed predicted deleterious consequences. Notably, some of these DESs are previously reported as oncogenic variants, and in genes related to DNA damage repair, drug metabolism, gene regulation, the cell cycle, and immune response. In patients with BC, we uncovered DESs predominantly in immune response genes, and a subset with a significant association (log-rank test p < 0.05) between RNA editing level in LSR, SMPDL3B, HTRA4, and LL22NC03-80A10.6 genes, and progression-free survival. Our findings provide a landscape of RNA-edited sites that may be involved in drug response mechanisms, highlighting the value of A>I(G) RNA editing in clinical outcomes for BC.
dc.description.versionVersión Publicada
dc.identifier.citationBernal, Y. A., Blanco, A., Sagredo, E. A., Oróstica, K., Alfaro, I., Marcelain, K., & Armisén, R. (2024). A Comprehensive Analysis of the Effect of A>I(G) RNA-Editing Sites on Genotoxic Drug Response and Progression in Breast Cancer. Biomedicines, 12(4), 728. https://doi.org/10.3390/biomedicines12040728
dc.identifier.doihttps://doi.org/10.3390/biomedicines12040728
dc.identifier.urihttps://hdl.handle.net/11447/9198
dc.language.isoen
dc.subjectADAR1
dc.subjectPARP inhibitors
dc.subjectRNA editing
dc.subjectRNA-edited sites
dc.subjectalkylating agents
dc.subjectanthracyclines
dc.subjectbreast cancer
dc.subjectcancer therapy
dc.subjectdrug sensitivity
dc.titleA Comprehensive Analysis of the Effect of A>I(G) RNA-Editing Sites on Genotoxic Drug Response and Progression in Breast Cancer
dc.typeArticle
dcterms.accessRightsAcceso Abierto
dcterms.sourceBiomedicines
dspace.entity.typePublication

Files

Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
A Comprehensive Analysis of the Effect of A.pdf
Size:
9.13 MB
Format:
Adobe Portable Document Format
Description:
Texto Completo
Download
License bundle
Now showing 1 - 1 of 1
No Thumbnail Available
Name:
license.txt
Size:
347 B
Format:
Item-specific license agreed upon to submission
Description:
Download

Collections

Artículos Medicina y Ciencias de la Salud

Implementado por OpenGeek Services