Abstract
BackgroundBladder cancer is having a gradually increasing incidence in China. Except for the traditional chemotherapy drugs, there are no emerging new drugs for almost 30 years in bladder cancer. New potential therapeutic targets and biomarkers are urgently needed.MethodsBORA is the activator of kinase Aurora A and plays an important role in cell cycle progression. To investigate the function of BORA in BCa, we established BORA knockdown and overexpression cell models for in vitro studies, xenograft and pulmonary metastasis mouse models for in vivo studies.ResultsOur results indicated that BORA was upregulated in human bladder cancer (BCa) compared to the normal bladder and paracancerous tissues at transcriptional and translational levels. We found that BORA was positively related to BCa cell proliferation. Furthermore, BORA knockdown induced cell cycle arrest in G2/M phase while BORA overexpression decreased the proportion of cells in G2/M, associated with PLK1–CDC25C–CDK1 alteration. Interestingly, we observed that knockdown of BORA inhibited BCa cell migration and invasion, accompanied with alterations of epithelial–mesenchymal transition (EMT) pathway related proteins. In vivo studies confirmed the inhibition effect of BORA knockdown on BCa cell growth and migration.ConclusionsOur study indicates that BORA regulates BCa cell cycle and growth, meanwhile influences cell motility by EMT, and could be a novel biomarker and potential therapeutic target in BCa.
Highlights
Bladder cancer is having a gradually increasing incidence in China
Upregulated BORA in bladder cancer (BCa) tissues We searched Oncomine database to find that mRNA expression of BORA was significantly increased in BCa compared to normal bladder (Fig. 1a)
We verified the mRNA and protein expression of BORA in BCa and paracancerous tissues collected from our hospital. qRT-PCR results revealed that BORA was Positive regulation of BORA in BCa cell proliferation To establish BORA knockdown cell model, UM-UC-3 and 5637 cells were transfected with three BORA-target-siRNAs
Summary
Bladder cancer is having a gradually increasing incidence in China. Except for the traditional chemotherapy drugs, there are no emerging new drugs for almost 30 years in bladder cancer. As the ninth most common cancer worldwide [1], bladder cancer (BCa) is having a gradually increasing incidence in China [2]. Chemotherapy based on cisplatin has improved the outcome modestly. For cisplatin-ineligible patients, T-cell checkpoint inhibitors have presented some benefits to BORA encoded protein activates kinase Aurora A, and is very important in spindle assembly, centrosome maturation and the process of mitosis. BORA was identified as a cell cycle co-factor protein of Aurora A in the first place [8]. PLK1 and Aurora A are critical regulators of cell cycle, which has
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