Tesis Doctorales
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Browsing Tesis Doctorales by Author "Bernal Gómez, Yanara Alejandra"
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Item A>I(G) RNA Editing in genotoxic drug response in breast cancer(Universidad del Desarrollo. Facultad de Medicina, 2025) Bernal Gómez, Yanara Alejandra; Armisen Yañez, RicardoBreast cancer (BC) is the most common malignancy among women and a leading cause of cancer-related mortality. While advancements in genomic technologies have improved the understanding of BC biology, therapeutic resistance remains a significant challenge, particularly to genotoxic drugs. This study explores the association of A>I(G) RNA editing, a post-transcriptional modification mediated by ADAR enzymes, in drug response and resistance in BC. A>I(G) RNA editing modifies adenosine to inosine in double-stranded RNA, potentially altering RNA stability, splicing, and protein function. The results identified ADAR1-mediated A>I(G) RNA editing sites associated with sensitivity or resistance to genotoxic drugs in BC cell lines. These sites, predominantly located in non-coding regions, were functionally linked to genes involved in DNA damage repair, immune response, and cancer progression. Furthermore, RNA editing levels in genes such as LSR, SMPDL3B, HTRA4, and LL22NC03-80A10.6 were significantly associated with progression-free survival in BC patients, highlighting their potential as prognostic biomarkers. In addition, multi-omics data were integrated using machine learning tools to predict the risk of therapy non-response in BC. This approach identified ADAR1 mediated RNA-edited sites, such as those in KDM4B, miRNA200/TTLL10-AS1, and BEST1, as key predictive variables alongside clinically relevant features. These sites, primarily in non-coding regions, were associated with genes involved in histone demethylation, DNA damage repair (DDR), epithelial-mesenchymal transition (EMT), and cell proliferation. The predictive models demonstrated acceptable performance in distinguishing responder and non-responder patients, emphasizing the utility of combining transcriptomic, epitranscriptomic, and clinical data to predict therapy response and their potential as predictive biomarkers. This study advances the understanding of A>I(G) RNA editing as a contributor to drug resistance in BC and underscores its potential as a biomarker and therapeutic target. The findings highlight the importance of post-transcriptional modifications in precision medicine, offering new avenues for the development of personalized treatment strategies.