Verification of cell cycle-associated cyclin-dependent kinases facilitated prostate cancer progression by integrated bioinformatic analysis and experimental validation. Issue 8 (August 2022)

• Record Type: Journal Article
• Authors: Huang, Yean; Lu, Shuo; Chen, Yi; Qing, Yunhao; Wu, Ruji; Ma, Tan; Zhang, Zixiao; Wang, Yu; Li, Ke
• Is Part Of: Heliyon. Volume 8:Issue 8(2022)
• Publication Date: 2022-08
• Subjects: Prostate cancer -- Cell cycle-associated cyclin-dependent kinases -- Bioinformatic analysis -- Biochemical recurrence -- Prognosis; Research -- Periodicals; Medical sciences -- Periodicals; Natural history -- Periodicals; Social sciences -- Periodicals; Earth sciences -- Periodicals; Physical sciences -- Periodicals; 507.2
• DOI: 10.1016/j.heliyon.2022.e10081
• Languages: English
• ISSNs: 2405-8440

Abstract

Abstract: Introduction: 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. Methods: 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. Results: 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. Conclusions: 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. Highlights: ccCDKs were expressed at higher levels in prostate cancer tissues than in normal tissues. High expression of ccCDKs was associated with poor disease-free survival in prostate cancer patients. ccCDKs were enriched in the IL-18 signaling pathway and correlated with the infiltration of immune cells in prostate cancer. CDK3 promoted tumor progression in PCa cells and could be used to predict biochemical recurrence in PCa patients. Abstract : Prostate cancer; Cell cycle-associated cyclin-dependent kinases; Bioinformatic analysis; Biochemical recurrence; Prognosis.