High expression of Aurora-B is correlated with poor prognosis and drug resistance in non-small cell lung cancer

被引:53
作者
Yu, JingJing [1 ]
Zhou, Jing [1 ]
Xu, Fei [1 ]
Bai, Wei [1 ]
Zhang, Wei [1 ]
机构
[1] Nanchang Univ, Affiliated Hosp 1, Dept Resp Med, 17 Yong Wai St, Nanchang 330006, Jiangxi, Peoples R China
关键词
Aurora-B; Chemoresistance; NSCLC; Cisplatin; Paclitaxel; KINASE; CHEMORESISTANCE;
D O I
10.1177/1724600817753098
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Objective: Aurora kinase B (Aurora-B) is a crucial regulator of accurate mitosis. Abnormal Aurora-B expression is associated with aneuploidy and has been implicated in the pathogenesis and drug resistance in a variety of human cancers. However, little evidence is available regarding the role of Aurora-B in regulating drug response in non-small cell lung cancer (NSCLC), which is the most common type of lung cancer, and is characterized with poor prognosis and high mortality. Method: In the current study, we investigated the association of Aurora-B with the prognosis of NSCLC patients, and we also used the latest CRISPR/Cas9 system to explore the regulatory role of Aurora-B in NSCLC cells developing resistance to cisplatin (CDDP) and paclitaxel. Results: We found that Aurora-B was correlated with significantly reduced overall survival and disease-free survival in NSCLC patients. Aurora-B overexpression was also observed in NSCLC cells developing impaired response to both CDDP and paclitaxel. Moreover, we found, for the first time, that Aurora-B may impair NSCLC drug response by disturbing cell proliferation and inhibiting p53-related DNA damage response and apoptotic pathway, while the knockout of Aurora-B resensitized NSCLC cells to chemo drugs by ensuring correct chromosome segregation and restoring p53 expression. Conclusions: Our results demonstrated the association of Aurora-B with chemoresistance in NSCLC, which may finally contribute to the poor prognosis of NSCLC patients. We also suggested Aurora-B as a promising therapeutic target in NSCLC treatment.
引用
收藏
页码:215 / 221
页数:7
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