The RNA editing landscape in acute myeloid leukemia reveals associations with disease mutations and clinical outcome

Meduri, Eshwar; Breeze, Charles E.; Marando, Ludovica; Richardson, Simon; Huntly, Brian J.P.

doi:10.1016/j.isci.2022.105622

Cited by 2 publications

(2 citation statements)

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“…Within our BC cell lines, a positive correlation emerged between ADAR1 expression and the global editing index. A trend also was found in cancer cell lines [31] and in patients with acute myeloid leukemia (AML) [32]. This correlation suggests that the global editing index may only partially explain the RNA-editing activity of ADAR1, emphasizing the need for a more targeted approach focusing on specific RNA-edited sites.…”

Section: Discussionmentioning

confidence: 90%

“…Importantly, an RNA editing signature has been identified as a prognostic and predictive biomarker in gastric cancer [38], and a response to immunotherapy in lung cancer [39]. Additionally, RNA-edited sites, including the specific site in SOCS2-AS1 at Chr12:935,429,429 (T/C) (n = 32), has been linked to survival probability in AML patients compared to non-edited sites (n = 119) [32]. Although these DESs could be relevant to drug response, we aimed to address sites with clinical significance.…”

Section: Discussionmentioning

confidence: 99%

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

Bernal,

Blanco,

Sagredo

et al. 2024

Biomedicines

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Dysregulated 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.

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Section: Discussionmentioning

confidence: 90%

Section: Discussionmentioning

confidence: 99%

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

Bernal,

Blanco,

Sagredo

et al. 2024

Biomedicines

View full text Add to dashboard Cite

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ADAR-Mediated A>I(G) RNA Editing in the Genotoxic Drug Response of Breast Cancer

Bernal,

Durán,

Solar

et al. 2024

IJMS

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Epitranscriptomics is a field that delves into post-transcriptional changes. Among these modifications, the conversion of adenosine to inosine, traduced as guanosine (A>I(G)), is one of the known RNA-editing mechanisms, catalyzed by ADARs. This type of RNA editing is the most common type of editing in mammals and contributes to biological diversity. Disruption in the A>I(G) RNA-editing balance has been linked to diseases, including several types of cancer. Drug resistance in patients with cancer represents a significant public health concern, contributing to increased mortality rates resulting from therapy non-responsiveness and disease progression, representing the greatest challenge for researchers in this field. The A>I(G) RNA editing is involved in several mechanisms over the immunotherapy and genotoxic drug response and drug resistance. This review investigates the relationship between ADAR1 and specific A>I(G) RNA-edited sites, focusing particularly on breast cancer, and the impact of these sites on DNA damage repair and the immune response over anti-cancer therapy. We address the underlying mechanisms, bioinformatics, and in vitro strategies for the identification and validation of A>I(G) RNA-edited sites. We gathered databases related to A>I(G) RNA editing and cancer and discussed the potential clinical and research implications of understanding A>I(G) RNA-editing patterns. Understanding the intricate role of ADAR1-mediated A>I(G) RNA editing in breast cancer holds significant promise for the development of personalized treatment approaches tailored to individual patients’ A>I(G) RNA-editing profiles.

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The RNA editing landscape in acute myeloid leukemia reveals associations with disease mutations and clinical outcome

Cited by 2 publications

References 57 publications

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

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

ADAR-Mediated A>I(G) RNA Editing in the Genotoxic Drug Response of Breast Cancer

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