Aurora kinase A is a biomarker for bladder cancer detection and contributes to its aggressive behavior

Aaron Mobley, Shizhen Zhang, Jolanta Bondaruk, Yan Wang, Tadeusz Majewski, Nancy P. Caraway, Li Huang, Einav Shoshan, Guermarie Velazquez-Torres, Giovanni Nitti, Sangkyou Lee, June Goo Lee, Enrique Fuentes-Mattei, Daniel Willis, Li Zhang, Charles C. Guo, Hui Yao, Keith Baggerly, Yair Lotan, Seth P. LernerColin Dinney, David McConkey, Menashe Bar-Eli, Bogdan Czerniak

Research output: Contribution to journalArticle

Abstract

The effects of AURKA overexpression associated with poor clinical outcomes have been attributed to increased cell cycle progression and the development of genomic instability with aneuploidy. We used RNA interference to examine the effects of AURKA overexpression in human bladder cancer cells. Knockdown had minimal effects on cell proliferation but blocked tumor cell invasion. Whole genome mRNA expression profiling identified nicotinamide N-methyltransferase (NNMT) as a downstream target that was repressed by AURKA. Chromatin immunoprecipitation and NNMT promoter luciferase assays revealed that AURKA's effects on NNMT were caused by PAX3-mediated transcriptional repression and overexpression of NNMT blocked tumor cell invasion in vitro. Overexpression of AURKA and activation of its downstream pathway was enriched in the basal subtype in primary human tumors and was associated with poor clinical outcomes. We also show that the FISH test for the AURKA gene copy number in urine yielded a specificity of 79.7% (95% confidence interval [CI] = 74.2% to 84.1%), and a sensitivity of 79.6% (95% CI = 74.2% to 84.1%) with an AUC of 0.901 (95% CI = 0.872 to 0.928; P < 0.001). These results implicate AURKA as an effective biomarker for bladder cancer detection as well as therapeutic target especially for its basal type.

Original languageEnglish (US)
Article number40714
JournalScientific Reports
Volume7
DOIs
StatePublished - Jan 19 2017
Externally publishedYes

ASJC Scopus subject areas

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    Mobley, A., Zhang, S., Bondaruk, J., Wang, Y., Majewski, T., Caraway, N. P., Huang, L., Shoshan, E., Velazquez-Torres, G., Nitti, G., Lee, S., Lee, J. G., Fuentes-Mattei, E., Willis, D., Zhang, L., Guo, C. C., Yao, H., Baggerly, K., Lotan, Y., ... Czerniak, B. (2017). Aurora kinase A is a biomarker for bladder cancer detection and contributes to its aggressive behavior. Scientific Reports, 7, [40714]. https://doi.org/10.1038/srep40714