Department of Urology, Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215000, P.R. China.
Department of Urology, Xishan People's Hospital of Wuxi City, Wuxi, Jiangsu 214000, P.R. China.
Oncol Rep. 2022 Feb;47(2). doi: 10.3892/or.2021.8253. Epub 2021 Dec 31.
Dysregulation of the cell cycle contributes to tumor progression. Cell division cycle‑associated 3 (CDCA3) is a known trigger of mitotic entry and has been demonstrated to be constitutively upregulated in tumors. It is therefore associated with carcinogenic properties reported in various cancers. However, the role of CDCA3 in prostate cancer is unclear. In the present study, western blotting and analysis of gene expression profiling datasets determined that CDCA3 expression was upregulated in prostate cancer and was associated with a poor prognosis. CDCA3 knockdown in DU145 and PC‑3 cells led to decreased cell proliferation and increased apoptosis, with increased protein expression levels of cleaved‑caspase3. Further experiments demonstrated that downregulated CDCA3 expression levels induced G0/G1 phase arrest, which was attributed to increased p21 protein expression levels and decreased cyclin D1 expression levels via the regulation of NF‑κB signaling proteins (NFκB‑p105/p50, IKKα/β, and pho‑NFκB‑p65). In conclusion, these results indicated that CDCA3 may serve a crucial role in prostate cancer and consequently, CDCA3 knockdown may be used as a potential therapeutic target.
细胞周期失调导致肿瘤进展。细胞分裂周期相关蛋白 3（CDCA3）是有丝分裂进入的已知触发因素，并且已被证明在肿瘤中持续上调。因此，它与各种癌症中报道的致癌特性有关。然而，CDCA3 在前列腺癌中的作用尚不清楚。在本研究中，通过 Western blot 分析和基因表达谱数据集分析，确定 CDCA3 在前列腺癌中表达上调，并与预后不良相关。在 DU145 和 PC-3 细胞中敲低 CDCA3 导致细胞增殖减少和细胞凋亡增加，同时 cleaved-caspase3 蛋白表达水平升高。进一步的实验表明，下调 CDCA3 表达水平诱导 G0/G1 期停滞，这归因于 p21 蛋白表达水平增加和细胞周期蛋白 D1 表达水平降低，通过调节 NF-κB 信号蛋白（NFκB-p105/p50、IKKα/β 和 pho-NF-κB-p65）。综上所述，这些结果表明 CDCA3 可能在前列腺癌中发挥重要作用，因此，CDCA3 敲低可能作为一种潜在的治疗靶点。
