A Comprehensive RNA Study to Identify circRNA and miRNA Biomarkers for Docetaxel Resistance in Breast Cancer
To investigate the relationship between non-coding RNAs [especially circular RNAs (circRNAs)] and docetaxel resistance in breast cancer, and to find potential predictive biomarkers for taxane-containing therapies, we have performed transcriptome and microRNA (miRNA) sequencing for two established do...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2021
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8162208/ https://www.ncbi.nlm.nih.gov/pubmed/34055636 http://dx.doi.org/10.3389/fonc.2021.669270 |
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author | Huang, Peide Li, Fengyu Mo, Zongchao Geng, Chunyu Wen, Fang Zhang, Chunyan Guo, Jia Wu, Song Li, Lin Brünner, Nils Stenvang, Jan |
author_facet | Huang, Peide Li, Fengyu Mo, Zongchao Geng, Chunyu Wen, Fang Zhang, Chunyan Guo, Jia Wu, Song Li, Lin Brünner, Nils Stenvang, Jan |
author_sort | Huang, Peide |
collection | PubMed |
description | To investigate the relationship between non-coding RNAs [especially circular RNAs (circRNAs)] and docetaxel resistance in breast cancer, and to find potential predictive biomarkers for taxane-containing therapies, we have performed transcriptome and microRNA (miRNA) sequencing for two established docetaxel-resistant breast cancer (DRBC) cell lines and their docetaxel-sensitive parental cell lines. Our analyses revealed differences between circRNA signatures in the docetaxel-resistant and -sensitive breast cancer cells, and discovered circRNAs generated by multidrug-resistance genes in taxane-resistant cancer cells. In DRBC cells, circABCB1 was identified and validated as a circRNA that is strongly up-regulated, whereas circEPHA3.1 and circEPHA3.2 are strongly down-regulated. Furthermore, we investigated the potential functions of these circRNAs by bioinformatics analysis, and miRNA analysis was performed to uncover potential interactions between circRNAs and miRNAs. Our data showed that circABCB1, circEPHA3.1 and circEPHA3.2 may sponge up eight significantly differentially expressed miRNAs that are associated with chemotherapy and contribute to docetaxel resistance via the PI3K-Akt and AGE-RAGE signaling pathways. We also integrated differential expression data of mRNA, long non-coding RNA, circRNA, and miRNA to gain a global profile of multi-level RNA changes in DRBC cells, and compared them with changes in DNA copy numbers in the same cell lines. We found that Chromosome 7 q21.12-q21.2 was a common region dominated by multi-level RNA overexpression and DNA amplification, indicating that overexpression of the RNA molecules transcribed from this region may result from DNA amplification during stepwise exposure to docetaxel. These findings may help to further our understanding of the mechanisms underlying docetaxel resistance in breast cancer. |
format | Online Article Text |
id | pubmed-8162208 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-81622082021-05-29 A Comprehensive RNA Study to Identify circRNA and miRNA Biomarkers for Docetaxel Resistance in Breast Cancer Huang, Peide Li, Fengyu Mo, Zongchao Geng, Chunyu Wen, Fang Zhang, Chunyan Guo, Jia Wu, Song Li, Lin Brünner, Nils Stenvang, Jan Front Oncol Oncology To investigate the relationship between non-coding RNAs [especially circular RNAs (circRNAs)] and docetaxel resistance in breast cancer, and to find potential predictive biomarkers for taxane-containing therapies, we have performed transcriptome and microRNA (miRNA) sequencing for two established docetaxel-resistant breast cancer (DRBC) cell lines and their docetaxel-sensitive parental cell lines. Our analyses revealed differences between circRNA signatures in the docetaxel-resistant and -sensitive breast cancer cells, and discovered circRNAs generated by multidrug-resistance genes in taxane-resistant cancer cells. In DRBC cells, circABCB1 was identified and validated as a circRNA that is strongly up-regulated, whereas circEPHA3.1 and circEPHA3.2 are strongly down-regulated. Furthermore, we investigated the potential functions of these circRNAs by bioinformatics analysis, and miRNA analysis was performed to uncover potential interactions between circRNAs and miRNAs. Our data showed that circABCB1, circEPHA3.1 and circEPHA3.2 may sponge up eight significantly differentially expressed miRNAs that are associated with chemotherapy and contribute to docetaxel resistance via the PI3K-Akt and AGE-RAGE signaling pathways. We also integrated differential expression data of mRNA, long non-coding RNA, circRNA, and miRNA to gain a global profile of multi-level RNA changes in DRBC cells, and compared them with changes in DNA copy numbers in the same cell lines. We found that Chromosome 7 q21.12-q21.2 was a common region dominated by multi-level RNA overexpression and DNA amplification, indicating that overexpression of the RNA molecules transcribed from this region may result from DNA amplification during stepwise exposure to docetaxel. These findings may help to further our understanding of the mechanisms underlying docetaxel resistance in breast cancer. Frontiers Media S.A. 2021-05-14 /pmc/articles/PMC8162208/ /pubmed/34055636 http://dx.doi.org/10.3389/fonc.2021.669270 Text en Copyright © 2021 Huang, Li, Mo, Geng, Wen, Zhang, Guo, Wu, Li, Brünner and Stenvang https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Oncology Huang, Peide Li, Fengyu Mo, Zongchao Geng, Chunyu Wen, Fang Zhang, Chunyan Guo, Jia Wu, Song Li, Lin Brünner, Nils Stenvang, Jan A Comprehensive RNA Study to Identify circRNA and miRNA Biomarkers for Docetaxel Resistance in Breast Cancer |
title | A Comprehensive RNA Study to Identify circRNA and miRNA Biomarkers for Docetaxel Resistance in Breast Cancer |
title_full | A Comprehensive RNA Study to Identify circRNA and miRNA Biomarkers for Docetaxel Resistance in Breast Cancer |
title_fullStr | A Comprehensive RNA Study to Identify circRNA and miRNA Biomarkers for Docetaxel Resistance in Breast Cancer |
title_full_unstemmed | A Comprehensive RNA Study to Identify circRNA and miRNA Biomarkers for Docetaxel Resistance in Breast Cancer |
title_short | A Comprehensive RNA Study to Identify circRNA and miRNA Biomarkers for Docetaxel Resistance in Breast Cancer |
title_sort | comprehensive rna study to identify circrna and mirna biomarkers for docetaxel resistance in breast cancer |
topic | Oncology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8162208/ https://www.ncbi.nlm.nih.gov/pubmed/34055636 http://dx.doi.org/10.3389/fonc.2021.669270 |
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