Huang Yean, Lu Shuo, Chen Yi, Qing Yunhao, Wu Ruji, Ma Tan, Zhang Zixiao, Wang Yu, Li Ke
Department of Urology, The Third Affiliated Hospital of Sun Yat-sen University, Tianhe Road 600, Guangzhou 510630, China.
Department of Surgery, Su Fengxi Clinic, Zhongshan 2nd Rd 54th and 56th, Yuexiu District, Guangzhou 510000, China.
Heliyon. 2022 Aug 11;8(8):e10081. doi: 10.1016/j.heliyon.2022.e10081. eCollection 2022 Aug.
Cell cycle-associated cyclin-dependent kinases (ccCDKs) are essential regulators known to control cell division and facilitate tumorigenesis and progression. However, there is currently no comprehensive study of distinct ccCDKs in prostate cancer (PCa). The purpose of this study was to determine the value of ccCDK expression in predicting the prognosis of patients with PCa and to identify the gene functions of ccCDK in PCa.
The UALCAN databases were analyzed to examine the expression of CDKs in prostate cancer. The Human Protein Atlas was used to verify the expression of CDKs online. Then, we assessed the prognostic values of CDKs using GEPIA. GeneMANIA and Metascape analyses were used to predict biological functions. We analyzed the mutation of CDKs by cBioPortal. The TIMER database was used to evaluate the correlation of CDKs and immune infiltration. The expression of CDKs in tissue was examined through quantitative real-time polymerase chain reaction. After that, we focused on CDK3 and identified the expression of CDK3 by immunohistochemistry and western blot. The functions of CDK3 in C4-2 cell proliferation were determined by CCK-8 assays. C4-2 cells were tested for their ability to invade and migrate through transwell and wound healing assays.
The results showed that CDK1/3/4/5/6/16 was expressed at relatively higher levels in PCa tissues than in normal tissues. Patients with low expression of CDK1/3/5/16 exhibited significantly better disease-free survival than those with high expression. ccCDKs were enriched in the IL-18 signaling pathway and correlated with the infiltration of immune cells in PCa. Moreover, our cohort study data verified that there were significantly higher expression of CDK1/3/5/16 in PCa tissues compared to benign prostate hyperplasia tissues, and CDK3 was remarkably associated with a shorter progression-free survival for biochemical recurrence in PCa patients. CDK3 was positively expressed in PCa cells and tissues, and functional experiments demonstrated that silencing CDK3 inhibited PCa cell proliferation, migration, and invasion.
Our study provides new evidence of ccCDKS in promoting PCa progression and implies that CDK3 may serve as an oncogene in PCa and may be valuable in the prognosis of biochemical recurrence in PCa patients.
细胞周期相关的细胞周期蛋白依赖性激酶（ccCDKs）是已知的控制细胞分裂、促进肿瘤发生和进展的重要调节因子。然而，目前尚无关于前列腺癌（PCa）中不同ccCDKs的全面研究。本研究的目的是确定ccCDK表达在预测PCa患者预后中的价值，并确定ccCDK在PCa中的基因功能。
分析UALCAN数据库以检测前列腺癌中CDKs的表达。使用人类蛋白质图谱在线验证CDKs的表达。然后，我们使用GEPIA评估CDKs 的预后价值。使用GeneMANIA和Metascape分析来预测生物学功能。我们通过cBioPortal分析CDKs的突变。使用TIMER数据库评估CDKs与免疫浸润的相关性。通过定量实时聚合酶链反应检测组织中CDKs的表达。之后，我们聚焦于CDK3，并通过免疫组织化学和蛋白质免疫印迹法确定CDK3的表达。通过CCK-8试验确定CDK3在C４-2细胞增殖中的功能。通过Transwell和伤口愈合试验检测C4-2细胞的侵袭和迁移能力。
结果显示，CDK1/3/4/5/6/16在PCa组织中的表达水平相对高于正常组织。CDK1/3/5/16低表达的患者无病生存期明显优于高表达患者。ccCDKs在IL-18信号通路中富集，并与PCa中的免疫细胞浸润相关。此外，我们的队列研究数据证实，与良性前列腺增生组织相比，PCa组织中CDK1/3/5/16的表达明显更高，并且CDK3与PCa患者生化复发的无进展生存期较短显著相关。CDK3在PCa细胞和组织中呈阳性表达，功能实验表明，沉默CDK3可抑制PCa细胞的增殖、迁移和侵袭。
我们的研究为ccCDKs促进PCa进展提供了新证据，并表明CDK3可能作为PCa中的一种癌基因，在PCa患者生化复发的预后中可能具有重要价值。
