Department of Urology, Shaanxi Provincial People's Hospital, Xi'an, 710068, China.
Department of Physical Examination, Shaanxi Provincial People's Hospital, No.256 Youyi West Road, Xi'an, 710068, China.
J Bioenerg Biomembr. 2021 Apr;53(2):247-258. doi: 10.1007/s10863-021-09887-3. Epub 2021 Mar 10.
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.
吡咯啉-5-羧酸还原酶 1（PYCR1）在多种癌症的恶性进展中发挥重要作用。然而，PYCR1 在膀胱癌中的作用尚未得到充分研究。本研究旨在评估 PYCR1 在膀胱癌中的潜在相关性。我们的数据显示，PYCR1 在膀胱癌组织中表达增加，PYCR1 表达增加预示着生存率降低。在膀胱癌细胞系中，敲低 PYCR1 导致细胞生长和侵袭明显延迟，而过表达 PYCR1 则加速细胞增殖和侵袭。此外，PYCR1 敲低降低了磷酸化 Akt 的水平，并增强了 Wnt/β-catenin 信号通路的激活。Akt 抑制显著阻断了 PYCR1 过表达介导的 Wnt/β-catenin 信号通路的激活。此外，β-catenin 的过表达部分逆转了 PYCR1 敲低介导的肿瘤抑制。值得注意的是，PYCR1 敲低显著抑制了膀胱癌细胞在体内的肿瘤形成和生长。总之，这些数据表明，PYCR1 在膀胱癌中高表达，敲低 PYCR1 通过下调 Akt/Wnt/β-catenin 信号通路对肿瘤形成产生显著抑制作用。本研究提示 PYCR1 在促进膀胱癌进展中可能具有潜在作用，并表明 PYCR1 可作为治疗膀胱癌有吸引力和有前途的抗癌靶点。
