Long Non-coding RNA BLACAT1 Induces Tamoxifen Resistance in Human Breast Cancer by Regulating miR-503/Bcl-2 Axis
Rongfeng Qu,* Chunmei Hu,* Yan Tang, Qiong Yu, Guang Shi Department of Hematology and Oncology, The Second Hospital of Jilin University, Changchun 130041, Jilin, People’s Republic of China*These authors contributed equally to this workCorrespondence: Guang ShiDepartment of Hematology and O...
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Dove Medical Press
2020-03-01
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| Series: | Cancer Management and Research |
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| Online Access: | https://www.dovepress.com/long-non-coding-rna-blacat1-induces-tamoxifen-resistance-in-human-brea-peer-reviewed-article-CMAR |
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| author | Qu R Hu C Tang Y Yu Q Shi G |
| author_facet | Qu R Hu C Tang Y Yu Q Shi G |
| author_sort | Qu R |
| collection | DOAJ |
| description | Rongfeng Qu,* Chunmei Hu,* Yan Tang, Qiong Yu, Guang Shi Department of Hematology and Oncology, The Second Hospital of Jilin University, Changchun 130041, Jilin, People’s Republic of China*These authors contributed equally to this workCorrespondence: Guang ShiDepartment of Hematology and Oncology, The Second Hospital of Jilin University, No. 218 Ziqiang Street, Changchun 130041, Jilin, People’s Republic of ChinaEmail drshiguang_shju@163.comIntroduction: At present, drug resistance remains a major obstacle for breast cancer (BCa) patients who receive tamoxifen (TAM) chemotherapy. In this study, we aimed to investigate the functional role of long non-coding RNA BLACAT1 in the acquisition of TAM resistance in BCa.Methods: TAM-resistant BCa cells were derived by exposure to 1 μM of TAM for 6 months. The expression levels of BLACAT1 and miR-503 were detected by RT-qPCR analysis. Chemosensitivity of BCa cells to TAM was measured by MTT assay. Apoptosis of BCa cells was detected by flow cytometric analysis, and the expression levels of apoptosis-related proteins were detected by Western blot analysis. The direct binding relation between BLACAT1 and miR-503 was predicted by bioinformatics analysis and verified by dual-luciferase reporter assay.Results: Our findings showed that BLACAT1 was significantly upregulated in TAM-resistant BCa cells (MCF-7/TR and T47D/TR), and BLACAT1 knockdown markedly reduced the TAM resistance in these cells. Importantly, we observed that BLACAT1 might function as a competing endogenous RNA of miR-503 in MCF-7/TR and T47D/TR cells, thereby increasing the expression of oncogenic Bcl-2 protein. Rescue experiments showed that miR-503 inhibition partly blocked the inhibitory effect of BLACAT1 knockdown on TAM resistance of MCF-7/TR and T47D/TR cells.Conclusion: To conclude, this study revealed that overexpressed BLACAT1 induces TAM resistance in human BCa partly by regulating miR-503/Bcl-2 axis, potentially benefiting BCa treatment in the future.Keywords: breast cancer, tamoxifen resistance, long non-coding RNA BLACAT1, miR-503, Bcl-2 |
| first_indexed | 2024-12-14T00:40:20Z |
| format | Article |
| id | doaj.art-1ffe686f2f9f4686a61d5638555bf6d0 |
| institution | Directory Open Access Journal |
| issn | 1179-1322 |
| language | English |
| last_indexed | 2024-12-14T00:40:20Z |
| publishDate | 2020-03-01 |
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| spelling | doaj.art-1ffe686f2f9f4686a61d5638555bf6d02022-12-21T23:24:24ZengDove Medical PressCancer Management and Research1179-13222020-03-01Volume 121771177752393Long Non-coding RNA BLACAT1 Induces Tamoxifen Resistance in Human Breast Cancer by Regulating miR-503/Bcl-2 AxisQu RHu CTang YYu QShi GRongfeng Qu,* Chunmei Hu,* Yan Tang, Qiong Yu, Guang Shi Department of Hematology and Oncology, The Second Hospital of Jilin University, Changchun 130041, Jilin, People’s Republic of China*These authors contributed equally to this workCorrespondence: Guang ShiDepartment of Hematology and Oncology, The Second Hospital of Jilin University, No. 218 Ziqiang Street, Changchun 130041, Jilin, People’s Republic of ChinaEmail drshiguang_shju@163.comIntroduction: At present, drug resistance remains a major obstacle for breast cancer (BCa) patients who receive tamoxifen (TAM) chemotherapy. In this study, we aimed to investigate the functional role of long non-coding RNA BLACAT1 in the acquisition of TAM resistance in BCa.Methods: TAM-resistant BCa cells were derived by exposure to 1 μM of TAM for 6 months. The expression levels of BLACAT1 and miR-503 were detected by RT-qPCR analysis. Chemosensitivity of BCa cells to TAM was measured by MTT assay. Apoptosis of BCa cells was detected by flow cytometric analysis, and the expression levels of apoptosis-related proteins were detected by Western blot analysis. The direct binding relation between BLACAT1 and miR-503 was predicted by bioinformatics analysis and verified by dual-luciferase reporter assay.Results: Our findings showed that BLACAT1 was significantly upregulated in TAM-resistant BCa cells (MCF-7/TR and T47D/TR), and BLACAT1 knockdown markedly reduced the TAM resistance in these cells. Importantly, we observed that BLACAT1 might function as a competing endogenous RNA of miR-503 in MCF-7/TR and T47D/TR cells, thereby increasing the expression of oncogenic Bcl-2 protein. Rescue experiments showed that miR-503 inhibition partly blocked the inhibitory effect of BLACAT1 knockdown on TAM resistance of MCF-7/TR and T47D/TR cells.Conclusion: To conclude, this study revealed that overexpressed BLACAT1 induces TAM resistance in human BCa partly by regulating miR-503/Bcl-2 axis, potentially benefiting BCa treatment in the future.Keywords: breast cancer, tamoxifen resistance, long non-coding RNA BLACAT1, miR-503, Bcl-2https://www.dovepress.com/long-non-coding-rna-blacat1-induces-tamoxifen-resistance-in-human-brea-peer-reviewed-article-CMARbreast cancertamoxifen resistancelong non-coding rna blacat1mir-503bcl-2 |
| spellingShingle | Qu R Hu C Tang Y Yu Q Shi G Long Non-coding RNA BLACAT1 Induces Tamoxifen Resistance in Human Breast Cancer by Regulating miR-503/Bcl-2 Axis Cancer Management and Research breast cancer tamoxifen resistance long non-coding rna blacat1 mir-503 bcl-2 |
| title | Long Non-coding RNA BLACAT1 Induces Tamoxifen Resistance in Human Breast Cancer by Regulating miR-503/Bcl-2 Axis |
| title_full | Long Non-coding RNA BLACAT1 Induces Tamoxifen Resistance in Human Breast Cancer by Regulating miR-503/Bcl-2 Axis |
| title_fullStr | Long Non-coding RNA BLACAT1 Induces Tamoxifen Resistance in Human Breast Cancer by Regulating miR-503/Bcl-2 Axis |
| title_full_unstemmed | Long Non-coding RNA BLACAT1 Induces Tamoxifen Resistance in Human Breast Cancer by Regulating miR-503/Bcl-2 Axis |
| title_short | Long Non-coding RNA BLACAT1 Induces Tamoxifen Resistance in Human Breast Cancer by Regulating miR-503/Bcl-2 Axis |
| title_sort | long non coding rna blacat1 induces tamoxifen resistance in human breast cancer by regulating mir 503 bcl 2 axis |
| topic | breast cancer tamoxifen resistance long non-coding rna blacat1 mir-503 bcl-2 |
| url | https://www.dovepress.com/long-non-coding-rna-blacat1-induces-tamoxifen-resistance-in-human-brea-peer-reviewed-article-CMAR |
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