Abstract
Background
Hypoxia up-regulated 1 (HYOU1) was identified as a proto-oncogene and involved in tumorigenesis and progression in several cancer. Nonetheless, the biological function and mechanism of HYOU1 in bladder cancer (BCa) remian unclear.
Methods
The HYOU1 level in BCa tissues and cells was examined using RT-qPCR and western blot methods. The relationship between HYOU1 expression and clinicopathologic characteristics of BCa was analyzed. The biological role of HYOU1 on BCa cell proliferation, apoptosis, migration and invasion were analyzed via counting kit-8 (CCK-8), flow cytometry, wound healing and Transwell assays, respectively. The association between HYOU1 and the PI3K/AKT/Forkhead box O1 (FOXO1) signalling was assessed via western blot assay, meanwhile the the association of FOXO1 with HYOU1 was also investigated.
Results
HYOU1 was up-regulated in BCa tissues and cell lines, and the high level of HYOU1 was associated with bladder cancer histological grade and pathologic stage. Moreover, patients with high expression of HYOU1 showed poor overall survival from Kaplan-Meier Plotter. HYOU1 depletion impeded cell proliferation, migration and invasion, and induced cell apoptosis, while HYOU1 overexpression promoted cell proliferation, migration and invasion. Mechanically, our results showed that HYOU1 knockdown repressed PI3K/AKT/FOXO1 pathway and HYOU1 was negative regulated by FOXO1 in BCa. Significantly, we confirmed that the HYOU1/PI3K-AKT/FOXO1 negative feedback loop was involved in BCa cell proliferation, migration and invasion.
Conclusion
These findings revealed that HYOU1 acted as a pro-oncogene on BCa progression, and it will be a possible target for BCa treatment.
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Change history
18 April 2023
A Correction to this paper has been published: https://doi.org/10.1007/s11033-023-08325-4
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CC supervised the whole project, designed the experiments, and analyzed the data. WW performed the experiments, analyzed the data, wrote the manuscript. JX and XF contributed to the experiments and analyzed the data. CX prepared the figures. LG, LL, XQ, and ZM contributed to the experiments and provided technical support.
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The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013). The study was approved by the institutional ethics committee of Xiangya Changde Hospital (approval No. 201812628).
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Wang, W., Jiang, X., Xia, F. et al. HYOU1 promotes cell proliferation, migration, and invasion via the PI3K/AKT/FOXO1 feedback loop in bladder cancer. Mol Biol Rep 50, 453–464 (2023). https://doi.org/10.1007/s11033-022-07978-x
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DOI: https://doi.org/10.1007/s11033-022-07978-x