DOK3 promotes proliferation and inhibits apoptosis of prostate cancer via the NF-κB signaling pathway  

作　　者：Kun Jin Shi Qiu Bo Chen Zilong Zhang Chichen Zhang Xianghong Zhou Lu Yang Jianzhong Ai Qiang Wei 

机构地区：[1]Department of Urology and National Clinical Research Center for Geriatrics,West China Hospital,Sichuan University,Chengdu,Sichuan 610041,China [2]Center of Biomedical Big Data,West China Hospital,Sichuan University,Chengdu,Sichuan 610041,China [3]Department of Urology and Institute of Urology,West China Hospital,Sichuan University,Chengdu,Sichuan 610041,China

出　　处：《Chinese Medical Journal》2023年第4期423-432,共10页中华医学杂志（英文版）

基　　金：supported by the National Key Research and Development Program of China(No.2017YFC0908003).

摘　　要：Background: DOK3 (Downstream of kinase 3) is involved primarily with immune cell infiltration. Recent research reported the role of DOK3 in tumor progression, with opposite effects in lung cancer and gliomas;however, its role in prostate cancer (PCa) remains elusive. This study aimed to explore the role of DOK3 in PCa and to determine the mechanisms involved. Methods: To investigate the functions and mechanisms of DOK3 in PCa, we performed bioinformatic and biofunctional analyses. Samples from patients with PCa were collected from West China Hospital, and 46 were selected for the final correlation analysis. A lentivirus-based short hairpin ribonucleic acid (shRNA) carrier was established for silencing DOK3. A series of experiments involving the cell counting kit-8, bromodeoxyuridine, and flow cytometry assays were performed to identify cell proliferation and apoptosis. Changes in biomarkers from the nuclear factor kappa B (NF-κB) signaling pathway were detected to verify the relationship between DOK3 and the NF-κB pathway. A subcutaneous xenograft mouse model was performed to examine phenotypes after knocking down DOK3 in vivo . Rescue experiments with DOK3 knockdown and NF-κB pathway activation were designed to verify regulating effects. Results: DOK3 was up-regulated in PCa cell lines and tissues. In addition, a high level of DOK3 was predictive of higher pathological stages and worse prognoses. Similar results were observed with PCa patient samples. After silencing DOK3 in PCa cell lines 22RV1 and PC3, cell proliferation was significantly inhibited while apoptosis was promoted. Gene set enrichment analysis revealed that DOK3 function was enriched in the NF-κB pathway. Mechanism experiments determined that knockdown of DOK3 suppressed activation of the NF-κB pathway, increased the expressions of B-cell lymphoma-2 like 11 (BIM) and B-cell lymphoma-2 associated X (BAX), and decreased the expression of phosphorylated-P65 and X-linked inhibitor of apoptosis (XIAP). In the rescue experiments, pharmacological ac

关 键 词：Prostate cancer Downstream of kinase 3 PROGNOSIS Nuclear factor kappa B 

分 类 号：R737.25[医药卫生—肿瘤]