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The expression of miRNAs is associated with tumour genome instability and predicts the outcome of ovarian cancer patients treated with platinum agents

miRNAs, a class of short but stable noncoding RNA molecules, have been revealed to play important roles in the DNA damage response (DDR). However, their functions in cancer genome instability and the consequent clinical effect as the response to chemotherapy have not been fully elucidated. In this s...

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Autores principales: Wang, Tianzhen, Wang, Guangyu, Zhang, Xiaoxiao, Wu, Di, Yang, Lei, Wang, Guangyou, Hao, Dapeng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5677022/
https://www.ncbi.nlm.nih.gov/pubmed/29116111
http://dx.doi.org/10.1038/s41598-017-12259-w
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author Wang, Tianzhen
Wang, Guangyu
Zhang, Xiaoxiao
Wu, Di
Yang, Lei
Wang, Guangyou
Hao, Dapeng
author_facet Wang, Tianzhen
Wang, Guangyu
Zhang, Xiaoxiao
Wu, Di
Yang, Lei
Wang, Guangyou
Hao, Dapeng
author_sort Wang, Tianzhen
collection PubMed
description miRNAs, a class of short but stable noncoding RNA molecules, have been revealed to play important roles in the DNA damage response (DDR). However, their functions in cancer genome instability and the consequent clinical effect as the response to chemotherapy have not been fully elucidated. In this study, we utilized multidimensional TCGA data and the known miRNAs involved in DDR to identify a miRNA-regulatory network that responds to DNA damage. Additionally, based on the expression of ten miRNAs in this network, we developed a 10-miRNA-score that predicts defects in the homologous recombination (HR) pathway and genome instability in ovarian cancer. Importantly, consistent with the association between HR defects and improved response to chemotherapeutic agents, the 10-miRNA-score predicts the outcome of ovarian cancer patients treated with platinum agents, with a surprisingly better performance than the indexes of DNA damage. Therefore, our study demonstrates the implication of miRNA expression on cancer genome instability and provides an alternative method to identify DDR defects in patients who show the best effect with platinum drug treatment.
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spelling pubmed-56770222017-11-15 The expression of miRNAs is associated with tumour genome instability and predicts the outcome of ovarian cancer patients treated with platinum agents Wang, Tianzhen Wang, Guangyu Zhang, Xiaoxiao Wu, Di Yang, Lei Wang, Guangyou Hao, Dapeng Sci Rep Article miRNAs, a class of short but stable noncoding RNA molecules, have been revealed to play important roles in the DNA damage response (DDR). However, their functions in cancer genome instability and the consequent clinical effect as the response to chemotherapy have not been fully elucidated. In this study, we utilized multidimensional TCGA data and the known miRNAs involved in DDR to identify a miRNA-regulatory network that responds to DNA damage. Additionally, based on the expression of ten miRNAs in this network, we developed a 10-miRNA-score that predicts defects in the homologous recombination (HR) pathway and genome instability in ovarian cancer. Importantly, consistent with the association between HR defects and improved response to chemotherapeutic agents, the 10-miRNA-score predicts the outcome of ovarian cancer patients treated with platinum agents, with a surprisingly better performance than the indexes of DNA damage. Therefore, our study demonstrates the implication of miRNA expression on cancer genome instability and provides an alternative method to identify DDR defects in patients who show the best effect with platinum drug treatment. Nature Publishing Group UK 2017-11-07 /pmc/articles/PMC5677022/ /pubmed/29116111 http://dx.doi.org/10.1038/s41598-017-12259-w Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Wang, Tianzhen
Wang, Guangyu
Zhang, Xiaoxiao
Wu, Di
Yang, Lei
Wang, Guangyou
Hao, Dapeng
The expression of miRNAs is associated with tumour genome instability and predicts the outcome of ovarian cancer patients treated with platinum agents
title The expression of miRNAs is associated with tumour genome instability and predicts the outcome of ovarian cancer patients treated with platinum agents
title_full The expression of miRNAs is associated with tumour genome instability and predicts the outcome of ovarian cancer patients treated with platinum agents
title_fullStr The expression of miRNAs is associated with tumour genome instability and predicts the outcome of ovarian cancer patients treated with platinum agents
title_full_unstemmed The expression of miRNAs is associated with tumour genome instability and predicts the outcome of ovarian cancer patients treated with platinum agents
title_short The expression of miRNAs is associated with tumour genome instability and predicts the outcome of ovarian cancer patients treated with platinum agents
title_sort expression of mirnas is associated with tumour genome instability and predicts the outcome of ovarian cancer patients treated with platinum agents
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5677022/
https://www.ncbi.nlm.nih.gov/pubmed/29116111
http://dx.doi.org/10.1038/s41598-017-12259-w
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