Abstract
Breast cancer (BC) is a significant tissue for women’s health worldwide. The spindle assembly checkpoint protein family includes BUBR1 (Bub1-related kinase or MAD3/Bub1b). High expression of BUBR1 promotes cell cycle disorders, leading to cell carcinogenesis and cancer progression. However, the underlying molecular mechanism and the role of BUBR1 in BC progression are unclear. The published dataset was analyzed to evaluate the clinical relevance of BUBR1. BUBR1 was knocked down in BC cells using shRNA. The CCK-8 assay was used to measure the cell viability, and mRNA and protein expression levels were detected by RT-qPCR and Western blot (WB). Cell apoptosis and cell cycle were detected by flow cytometry. Subcutaneous xenograft model was used to assess in vivo tumor growth. BUBR1 was found to be highly expressed in BC. The high expression of BUBR1 was associated with poor prognosis of BC patients. Upon BUBR1 knockdown using shRNA, the proliferation and metastatic ability of cells were decreased. Moreover, the cells with BUBR1 knockdown underwent cell cycle arrest. And the results showed that BUBR1 loss inhibited the phosphorylation of TAK1/JNK. In vitro and in vivo studies indicated the knockdown of BUBR1 rendered the BC cells more sensitive to cisplatin. In summary, BUBR1 may be a potential therapeutic target for BC and targeting BUBR1 may help overcome cisplatin resistance in BC patients.
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The data that support the findings of this study are available from the corresponding author upon reasonable request.
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The authors would like to thank all the reviewers who participated in the paper, as well as MJEditor (www.mjeditor.com) for providing English editing services during the preparation of this manuscript.
Funding
This study was supported by National Key Research and Development (R&D) Program of China (No. 2022YFF0710503, to Y.D.), Jilin Scientific and Technological Development Program (No. 20230505037ZP, to Y.D.), and Natural Science Foundation of Jilin Province (No. 20210101364JC, to Y.D.).
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Conceptualization, Yu Ding and Yiran Lu; methodology, RuiQing Wang; software, Song He; validation, Song He and Qing Zhang; formal analysis, Yiran Lu; investigation, Yu Ding; resources, Yu Ding; data curation, Yiran Lu; writing—original draft preparation, Yu Ding and Yiran Lu; writing—review and editing, Yu Ding, Yiran Lu and Song He; visualization, Jiahui Wei; supervision, Jiahui Wei and Jinping Hu; project administration, Yu Ding and Ruiqing Wang; funding acquisition, Yu Ding and Jinping Hu. All the authors have read and agreed to the published version of the manuscript.
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The study was conducted in accordance with the Declaration of Helsinki, and approved by the Medical Ethics Committee of Jilin University Second Hospital (April 6, 2023) for studies involving humans. The animal study protocol was approved by the Experimental Animal Welfare Ethics Committee of Jilin University (Approval number: SY202207300, July 8, 2022) for studies involving animals.
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Informed consent was obtained from all subjects involved in the study. Written informed consent has been obtained from the patient(s) to publish this paper.
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Lu, Y., Wang, R., He, S. et al. Downregulation of BUBR1 regulates the proliferation and cell cycle of breast cancer cells and increases the sensitivity of cells to cisplatin. In Vitro Cell.Dev.Biol.-Animal 59, 778–789 (2023). https://doi.org/10.1007/s11626-023-00823-w
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DOI: https://doi.org/10.1007/s11626-023-00823-w