Downregulation of BUBR1 regulates the proliferation and cell cycle of breast cancer cells and increases the sensitivity of cells to cisplatin

被引:1
作者
Lu, Yiran [1 ]
Wang, Ruiqing [2 ]
He, Song [1 ]
Zhang, Qing [1 ]
Wei, Jiahui [1 ]
Hu, Jinping [1 ]
Ding, Yu [1 ]
机构
[1] Jilin Univ, Coll Anim Sci, Dept Lab Anim, Changchun 130062, Jilin, Peoples R China
[2] Second Hosp Jilin Univ, Eye Ctr, Ziqiang St 218, Changchun 130041, Jilin, Peoples R China
关键词
Breast cancer; BUBR1; TAK1/JNK; Cell cycle; Cisplatin sensitivity; ACTIVATION;
D O I
10.1007/s11626-023-00823-w
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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.
引用
收藏
页码:778 / 789
页数:12
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