| Summary: | 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
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