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High expression of Aurora-B is correlated with poor prognosis and drug resistance in non-small cell lung cancer.
- Source :
-
The International journal of biological markers [Int J Biol Markers] 2018 May; Vol. 33 (2), pp. 215-221. Date of Electronic Publication: 2018 Apr 30. - Publication Year :
- 2018
-
Abstract
- 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.<br />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.<br />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.<br />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.
- Subjects :
- A549 Cells
Apoptosis drug effects
Carcinoma, Non-Small-Cell Lung genetics
Carcinoma, Non-Small-Cell Lung pathology
Cell Proliferation drug effects
Cisplatin administration & dosage
Cisplatin adverse effects
Disease-Free Survival
Drug Resistance, Neoplasm genetics
Female
Gene Expression Regulation, Neoplastic drug effects
Humans
Male
Paclitaxel administration & dosage
Paclitaxel adverse effects
Aurora Kinase B genetics
Carcinoma, Non-Small-Cell Lung drug therapy
Drug Resistance, Neoplasm drug effects
Prognosis
Subjects
Details
- Language :
- English
- ISSN :
- 1724-6008
- Volume :
- 33
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- The International journal of biological markers
- Publication Type :
- Academic Journal
- Accession number :
- 29707994
- Full Text :
- https://doi.org/10.1177/1724600817753098