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Published in: Medical Oncology 2/2010

01-06-2010 | Original Paper

Systematic analysis of microRNA involved in resistance of the MCF-7 human breast cancer cell to doxorubicin

Authors: Guo-Qing Chen, Zhi-Wei Zhao, Hong-Ying Zhou, Yuan-Jie Liu, Hui-Jun Yang

Published in: Medical Oncology | Issue 2/2010

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Abstract

Multidrug resistance remains a major clinical obstacle to successful treatment of breast cancer and leads to poor prognosis for the patients. Recently studies have shown that microRNAs play an important role in breast cancer cell resistance to chemotherapeutic agents. In this study, microRNA expression profiles of MCF-7/AdrVp and MCF-7 were analyzed using microarray and the results were confirmed by real-time RT-polymerase chain reaction. Gene Ontology (GO) and pathways mapping tools were employed to analyse systemically the biological processes and signaling pathways affected by differential expression microRNAs. Here, we showed that 181 human microRNAs were differentially expressed between two cell lines. Compared to MCF-7 cells, there were 16 microRNAs down-regulated and 165 microRNAs up-regulated in MCF-7/AdrVp. Western blot confirmed the correlation between specific microRNA expression and corresponding changes in protein levels of their targets, specifically those that have a documented role in cancer drug resistance. Furthermore, we validated that signaling pathway highlighted in the study was involved in drug resistance. These results indicated that breast cancer cell resistant to chemotherapy was associated with a group of microRNAs. GO and pathway mapping are valid and effective approach to analyse the function of microRNAs and the results could be a guideline for further investigation.
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Literature
15.
go back to reference Nakajima G, Hayashi K, Xi Y, et al. Non-coding microRNAs hsa-let-7g and hsa-miR-181b are associated with chemoresponse to S-1 in colon cancer. Cancer Genomics Proteomics. 2006;3(5):317–24.PubMed Nakajima G, Hayashi K, Xi Y, et al. Non-coding microRNAs hsa-let-7g and hsa-miR-181b are associated with chemoresponse to S-1 in colon cancer. Cancer Genomics Proteomics. 2006;3(5):317–24.PubMed
16.
go back to reference Chen YN, Mickley LA, Schwartz AM, et al. Characterization of doxorubicin-resistant human breast cancer cells which display overexpression of a novel resistance-related membrane protein. J Biol Chem. 1990;265(17):10073–80.PubMed Chen YN, Mickley LA, Schwartz AM, et al. Characterization of doxorubicin-resistant human breast cancer cells which display overexpression of a novel resistance-related membrane protein. J Biol Chem. 1990;265(17):10073–80.PubMed
18.
go back to reference Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-delta delta C(T)) method. Methods. 2001;25(4):402–8.CrossRefPubMed Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-delta delta C(T)) method. Methods. 2001;25(4):402–8.CrossRefPubMed
20.
go back to reference Huang da W, Sherman BT, Tan Q, et al. DAVID Bioinformatics Resources: expanded annotation database and novel algorithms to better extract biology from large gene lists. Nucleic Acids Res. 2007;35(Web Server issue):W169–75.CrossRefPubMed Huang da W, Sherman BT, Tan Q, et al. DAVID Bioinformatics Resources: expanded annotation database and novel algorithms to better extract biology from large gene lists. Nucleic Acids Res. 2007;35(Web Server issue):W169–75.CrossRefPubMed
22.
go back to reference Nam S, Kim B, Shin S, Lee S. miRGator: an integrated system for functional annotation of microRNAs. Nucleic Acids Res. 2008;36(Database issue):D159–64.PubMed Nam S, Kim B, Shin S, Lee S. miRGator: an integrated system for functional annotation of microRNAs. Nucleic Acids Res. 2008;36(Database issue):D159–64.PubMed
24.
27.
30.
go back to reference Michael MZ, O’ Connor SM, van Holst Pellekaan NG, et al. Reduced accumulation of specific microRNAs in colorectal neoplasia. Mol Cancer Res. 2003;1(12):882–91.PubMed Michael MZ, O’ Connor SM, van Holst Pellekaan NG, et al. Reduced accumulation of specific microRNAs in colorectal neoplasia. Mol Cancer Res. 2003;1(12):882–91.PubMed
33.
go back to reference Adams BD, Furneaux H, White BA. The micro-ribonucleic acid (miRNA) miR-206 targets the human estrogen receptor-alpha (ERalpha) and represses ERalpha messenger RNA and protein expression in breast cancer cell lines. Mol Endocrinol. 2007;21(5):1132–47. doi:10.1210/me.2007-0022.CrossRefPubMed Adams BD, Furneaux H, White BA. The micro-ribonucleic acid (miRNA) miR-206 targets the human estrogen receptor-alpha (ERalpha) and represses ERalpha messenger RNA and protein expression in breast cancer cell lines. Mol Endocrinol. 2007;21(5):1132–47. doi:10.​1210/​me.​2007-0022.CrossRefPubMed
37.
go back to reference Normanno N, Campiglio M, Maiello MR, et al. Breast cancer cells with acquired resistance to the EGFR tyrosine kinase inhibitor gefitinib show persistent activation of MAPK signaling. Breast Cancer Res Treat. 2008;112(1):25–33. doi:10.1007/s10549-007-9830-2.CrossRefPubMed Normanno N, Campiglio M, Maiello MR, et al. Breast cancer cells with acquired resistance to the EGFR tyrosine kinase inhibitor gefitinib show persistent activation of MAPK signaling. Breast Cancer Res Treat. 2008;112(1):25–33. doi:10.​1007/​s10549-007-9830-2.CrossRefPubMed
38.
go back to reference Nahta R, Yuan LX, Zhang B, et al. Insulin-like growth factor-I receptor/human epidermal growth factor receptor 2 heterodimerization contributes to trastuzumab resistance of breast cancer cells. Cancer Res. 2005;65(23):11118–28. doi:10.1158/0008-5472.CAN-04-3841.CrossRefPubMed Nahta R, Yuan LX, Zhang B, et al. Insulin-like growth factor-I receptor/human epidermal growth factor receptor 2 heterodimerization contributes to trastuzumab resistance of breast cancer cells. Cancer Res. 2005;65(23):11118–28. doi:10.​1158/​0008-5472.​CAN-04-3841.CrossRefPubMed
Metadata
Title
Systematic analysis of microRNA involved in resistance of the MCF-7 human breast cancer cell to doxorubicin
Authors
Guo-Qing Chen
Zhi-Wei Zhao
Hong-Ying Zhou
Yuan-Jie Liu
Hui-Jun Yang
Publication date
01-06-2010
Publisher
Springer US
Published in
Medical Oncology / Issue 2/2010
Print ISSN: 1357-0560
Electronic ISSN: 1559-131X
DOI
https://doi.org/10.1007/s12032-009-9225-9

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