HOXA10 promotes the development of bladder cancer through regulating FOSL1

Y.-P. Cui, M. Xie, W.-X. Pan, Z.-Y. Zhang, W.-F. Li

Department of Urology, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, China. lichen0612@163.com

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• Oncology

OBJECTIVE: This study was aimed to investigate the expression characteristics of HOXA10 in bladder cancer (BCa), and to further study whether it can promote the development of BCa via regulating FOSL1.

PATIENTS AND METHODS: The expression of HOXA10 was examined by quantitative Real Time-PCR (qRT-PCR) in 37 pairs of tumor tissue and paracancerous specimens of BCa patients; meanwhile, in BCa cell lines, the expression of HOXA10 was also verified using qRT-PCR. Subsequently, after HOXA10 knockdown model was constructed in BCa cell lines (EJ and J82) using lentivirus transfection, transwell, as well as wound healing assays, were performed to analyze the influence of the downregulation of HOXA10 on the biological function of BCa cells. Finally, Luciferase reporting assay and cell reverse experiment were applied to explore the specific interaction between HOXA10 and FOSL1.

RESULTS: The results of qRT-PCR indicated that the expression level of HOXA10 in BCa tissue samples was remarkably higher than that in adjacent normal ones, with a statistically significant difference. At the same time, the overall survival rate of patients with high expression of HOXA10 was found to be lower than those with low expression. Meanwhile, compared with cells in sh-NC group, the metastasis ability of BCa cells in sh-HOXA10 group was remarkably weakened. In addition, it was found that the levels of FOSL1 and HOXA10 were negatively correlated in BCa tissues. The result of the Luciferase reporter gene assay revealed that HOXA10 could be targeted by FOSL1 through certain binding sites between them. In addition, HOXA10 was found to be capable of further regulating the malignant progression of BCa by modulating FOSL1.

CONCLUSIONS: HOXA10 expression is remarkably elevated in BCa tissues and cell lines, which is closely relevant to the poor prognosis of BCa patients. In addition, HOXA10 may be able to accelerate BCa metastasis via modulating FOSL1 expression.

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