Abstract
Pyrroline-5-carboxylate reductase 1 (PYCR1) plays a significant role in the malignant progression of various cancers. However, the role of PYCR1 in bladder cancer has not been well studied. This study was performed to evaluate the potential relevance of PYCR1 in bladder cancer. Our data revealed that PYCR1 expression was increased in bladder cancer tissues, and increased expression of PYCR1 was predictive of decreased survival rates. In bladder cancer cell lines, knockdown of PYCR1 caused significantly retarded cell growth and invasion, while PYCR1 overexpression accelerated cellular proliferation and invasion. Moreover, PYCR1 knockdown decreased levels of phosphorylated Akt, and enhanced activation of Wnt/β-catenin signaling. Akt inhibition markedly abrogated of PYCR1 overexpression-mediated activation of Wnt/β-catenin signaling. In addition, overexpression of β-catenin partially reversed PYCR1 knockdown-mediated tumor suppression. Notably, PYCR1 knockdown significantly impeded tumor formation and growth in bladder cancer cells in vivo. In conclusion, these data demonstrate that PYCR1 is highly expressed in bladder cancer and knockdown of PYCR1 exerts a remarkable inhibitory effect on tumor formation via downregulation of Akt/Wnt/β-catenin signaling. Our study suggests a potential role for PYCR1 in promoting bladder cancer progression and indicates that PYCR1 may be utilized as an attractive and promising anticancer target for treatment of bladder cancer.
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The datasets generated and/or analyzed during the current study are available from the corresponding author on reasonable request.
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Shuangkuan Du designed the study, performed the experiments and drafted the manuscript. Yongjie Sui designed the study and revised the manuscript. Wei Ren performed the experiments. Jiancheng Zhou interpreted the data. Chun Du interpreted the data. The author(s) read and approved the final manuscript.
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Research was carried out with the approval of Ethics Committee of Shaanxi Provincial People’s Hospital and was conducted in accordance with the principles of the Helsinki Declaration. Animal experiments were performed with the approval of the Ethics Committee of Shaanxi Provincial People’s Hospital.
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Du, S., Sui, Y., Ren, W. et al. PYCR1 promotes bladder cancer by affecting the Akt/Wnt/β-catenin signaling. J Bioenerg Biomembr 53, 247–258 (2021). https://doi.org/10.1007/s10863-021-09887-3
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DOI: https://doi.org/10.1007/s10863-021-09887-3