Tamoxifen resistance-related ceRNA network for breast cancer
Background: Tamoxifen (TMX) is one of the most widely used drugs to treat breast cancer (BC). However, acquired drug resistance is still a major obstacle to its application, rendering it crucial to explore the mechanisms of TMX resistance in BC. This aims of this study were to identify the mechanism...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-11-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2022.1023079/full |
| _version_ | 1811212354584576000 |
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| author | Zipeng Qiao Zipeng Qiao Yu Xing Yu Xing Qingquan Zhang Qingquan Zhang Yongjun Tang Yongjun Tang Ruifa Feng Weiyi Pang Weiyi Pang Weiyi Pang |
| author_facet | Zipeng Qiao Zipeng Qiao Yu Xing Yu Xing Qingquan Zhang Qingquan Zhang Yongjun Tang Yongjun Tang Ruifa Feng Weiyi Pang Weiyi Pang Weiyi Pang |
| author_sort | Zipeng Qiao |
| collection | DOAJ |
| description | Background: Tamoxifen (TMX) is one of the most widely used drugs to treat breast cancer (BC). However, acquired drug resistance is still a major obstacle to its application, rendering it crucial to explore the mechanisms of TMX resistance in BC. This aims of this study were to identify the mechanisms of TMX resistance and construct ceRNA regulatory networks in breast cancer.Methods: GEO2R was used to screen for differentially expressed mRNAs (DEmRNAs) leading to drug resistance in BC cells. MiRTarbase and miRNet were used to predict miRNAs and lncRNAs upstream, and the competing endogenous RNA (ceRNA) regulatory network of BC cell resistance was constructed by starBase. We used the Kaplan–Meier plotter and Gene Expression Profiling Interactive Analysis (GEPIA) to analyze the expression and prognostic differences of genes in the ceRNA network with core axis, and qRT-PCR was used to further verify the above conclusions.Results: We found that 21 DEmRNAs were upregulated and 43 DEmRNA downregulated in drug-resistant BC cells. DEmRNAs were noticeably enriched in pathways relevant to cancer. We then constructed a protein-protein interaction (PPI) network based on the STRING database and defined 10 top-ranked hub genes among the upregulated and downregulated DEmRNAs. The 20 DEmRNAs were predicted to obtain 113 upstream miRNAs and 501 lncRNAs. Among them, 7 mRNAs, 22 lncRNAs, and 11 miRNAs were used to structure the ceRNA regulatory network of drug resistance in BC cells. 4 mRNAs, 4 lncRNAs, and 3 miRNAs were detected by GEPIA and the Kaplan–Meier plotter to be significantly associated with BC expression and prognosis. The differential expression of the genes in BC cells was confirmed by qRT-PCR.Conclusion: The ceRNA regulatory network of TMX-resistant BC was successfully constructed and confirmed. This will provide an important resource for finding therapeutic targets for TMX resistance, where the discovery of candidate conventional mechanisms can aid clinical decision-making. In addition, this resource will help discover the mechanisms behind this type of resistance. |
| first_indexed | 2024-04-12T05:28:07Z |
| format | Article |
| id | doaj.art-72a780392eac46fabcc4e65ba2cec819 |
| institution | Directory Open Access Journal |
| issn | 2296-634X |
| language | English |
| last_indexed | 2024-04-12T05:28:07Z |
| publishDate | 2022-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-72a780392eac46fabcc4e65ba2cec8192022-12-22T03:46:13ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2022-11-011010.3389/fcell.2022.10230791023079Tamoxifen resistance-related ceRNA network for breast cancerZipeng Qiao0Zipeng Qiao1Yu Xing2Yu Xing3Qingquan Zhang4Qingquan Zhang5Yongjun Tang6Yongjun Tang7Ruifa Feng8Weiyi Pang9Weiyi Pang10Weiyi Pang11Guangxi Key Laboratory of Environmental Exposomics and Entire Lifecycle Heath, Guilin Medical University, Guilin, Guangxi, ChinaSchool of Public Health, Guilin Medical University, Guilin, Guangxi, ChinaGuangxi Key Laboratory of Environmental Exposomics and Entire Lifecycle Heath, Guilin Medical University, Guilin, Guangxi, ChinaSchool of Public Health, Guilin Medical University, Guilin, Guangxi, ChinaGuangxi Key Laboratory of Environmental Exposomics and Entire Lifecycle Heath, Guilin Medical University, Guilin, Guangxi, ChinaSchool of Public Health, Guilin Medical University, Guilin, Guangxi, ChinaGuangxi Key Laboratory of Environmental Exposomics and Entire Lifecycle Heath, Guilin Medical University, Guilin, Guangxi, ChinaSchool of Public Health, Guilin Medical University, Guilin, Guangxi, ChinaThe Second Affiliated Hospital of Guilin Medical University, Guilin, Guangxi, ChinaGuangxi Key Laboratory of Environmental Exposomics and Entire Lifecycle Heath, Guilin Medical University, Guilin, Guangxi, ChinaSchool of Public Health, Guilin Medical University, Guilin, Guangxi, ChinaSchool of Humanities and Management, Guilin Medical University, Guilin, Guangxi, ChinaBackground: Tamoxifen (TMX) is one of the most widely used drugs to treat breast cancer (BC). However, acquired drug resistance is still a major obstacle to its application, rendering it crucial to explore the mechanisms of TMX resistance in BC. This aims of this study were to identify the mechanisms of TMX resistance and construct ceRNA regulatory networks in breast cancer.Methods: GEO2R was used to screen for differentially expressed mRNAs (DEmRNAs) leading to drug resistance in BC cells. MiRTarbase and miRNet were used to predict miRNAs and lncRNAs upstream, and the competing endogenous RNA (ceRNA) regulatory network of BC cell resistance was constructed by starBase. We used the Kaplan–Meier plotter and Gene Expression Profiling Interactive Analysis (GEPIA) to analyze the expression and prognostic differences of genes in the ceRNA network with core axis, and qRT-PCR was used to further verify the above conclusions.Results: We found that 21 DEmRNAs were upregulated and 43 DEmRNA downregulated in drug-resistant BC cells. DEmRNAs were noticeably enriched in pathways relevant to cancer. We then constructed a protein-protein interaction (PPI) network based on the STRING database and defined 10 top-ranked hub genes among the upregulated and downregulated DEmRNAs. The 20 DEmRNAs were predicted to obtain 113 upstream miRNAs and 501 lncRNAs. Among them, 7 mRNAs, 22 lncRNAs, and 11 miRNAs were used to structure the ceRNA regulatory network of drug resistance in BC cells. 4 mRNAs, 4 lncRNAs, and 3 miRNAs were detected by GEPIA and the Kaplan–Meier plotter to be significantly associated with BC expression and prognosis. The differential expression of the genes in BC cells was confirmed by qRT-PCR.Conclusion: The ceRNA regulatory network of TMX-resistant BC was successfully constructed and confirmed. This will provide an important resource for finding therapeutic targets for TMX resistance, where the discovery of candidate conventional mechanisms can aid clinical decision-making. In addition, this resource will help discover the mechanisms behind this type of resistance.https://www.frontiersin.org/articles/10.3389/fcell.2022.1023079/fullbioinformaticsbreast cancerceRNATMX resistantlncRNAprognostic |
| spellingShingle | Zipeng Qiao Zipeng Qiao Yu Xing Yu Xing Qingquan Zhang Qingquan Zhang Yongjun Tang Yongjun Tang Ruifa Feng Weiyi Pang Weiyi Pang Weiyi Pang Tamoxifen resistance-related ceRNA network for breast cancer Frontiers in Cell and Developmental Biology bioinformatics breast cancer ceRNA TMX resistant lncRNA prognostic |
| title | Tamoxifen resistance-related ceRNA network for breast cancer |
| title_full | Tamoxifen resistance-related ceRNA network for breast cancer |
| title_fullStr | Tamoxifen resistance-related ceRNA network for breast cancer |
| title_full_unstemmed | Tamoxifen resistance-related ceRNA network for breast cancer |
| title_short | Tamoxifen resistance-related ceRNA network for breast cancer |
| title_sort | tamoxifen resistance related cerna network for breast cancer |
| topic | bioinformatics breast cancer ceRNA TMX resistant lncRNA prognostic |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2022.1023079/full |
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