Department of Otolaryngology‑Head and Neck Surgery, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310000, P.R. China.
Department of Preventive Medicine, Hangzhou Obstetrics and Gynecology Hospital, Hangzhou, Zhejiang 310008, P.R. China.
Mol Med Rep. 2023 May;27(5). doi: 10.3892/mmr.2023.12996. Epub 2023 Apr 13.
Nasopharyngeal carcinoma (NPC) is a primary malignancy that originates from the nasopharyngeal region. It has been demonstrated that a decrease in the expression level of cell division cycle gene 25A (CDC25A) suppresses cell viability and induces apoptosis in a variety of different types of cancer. However, at present, the role of CDC25A in NPC has yet to be fully elucidated. Therefore, the aim of the present study was to investigate the role of CDC25A in NPC progression and to explore the potential underlying mechanism. Reverse transcription‑quantitative PCR was performed to detect the relative mRNA levels of CDC25A and E2F transcription factor 1 (E2F1). Western blot analysis was subsequently used to determine the expression levels of CDC25A, Ki67, proliferating cell nuclear antigen (PCNA) and E2F1. CCK8 assay was employed to measure cell viability and flow cytometric analysis was employed to analyze the cell cycle. The binding sites between the CDC25A promoter and E2F1 were predicted using bioinformatics tools. Finally, luciferase reporter gene and chromatin immunoprecipitation assays were performed to verify the interaction between CDC25A and E2F1. The results obtained suggested that CDC25A is highly expressed in NPC cell lines and CDC25A silencing was found to inhibit cell proliferation, reduce the protein expression levels of Ki67 and PCNA and induce G1 arrest of NPC cells. Furthermore, E2F1 could bind CDC25A and positively regulate its expression at the transcriptional level. In addition, CDC25A silencing abolished the effects of E2F1 overexpression on cell proliferation and the cell cycle in NPC. Taken together, the findings of the present study showed that CDC25A silencing attenuated cell proliferation and induced cell cycle arrest in NPC and CDC25A was regulated by E2F1. Hence, CDC25A may be a promising therapeutic target for treatment of NPC.
鼻咽癌（NPC）是一种起源于鼻咽部的原发性恶性肿瘤。研究表明，细胞分裂周期基因 25A（CDC25A）表达水平的降低可抑制多种不同类型癌症的细胞活力并诱导细胞凋亡。然而，目前，CDC25A 在 NPC 中的作用尚未完全阐明。因此，本研究旨在探讨 CDC25A 在 NPC 进展中的作用，并探索其潜在的机制。采用逆转录-定量 PCR 检测 CDC25A 和 E2F 转录因子 1（E2F1）的相对 mRNA 水平。随后，采用 Western blot 分析检测 CDC25A、Ki67、增殖细胞核抗原（PCNA）和 E2F1 的表达水平。采用 CCK8 法检测细胞活力，采用流式细胞术分析细胞周期。使用生物信息学工具预测 CDC25A 启动子与 E2F1 之间的结合位点。最后，通过荧光素酶报告基因和染色质免疫沉淀实验验证 CDC25A 与 E2F1 之间的相互作用。研究结果表明，CDC25A 在 NPC 细胞系中高表达，沉默 CDC25A 可抑制细胞增殖，降低 Ki67 和 PCNA 蛋白表达水平，并诱导 NPC 细胞 G1 期阻滞。此外，E2F1 可与 CDC25A 结合，并在转录水平上正向调节其表达。此外，沉默 CDC25A 可消除 E2F1 过表达对 NPC 细胞增殖和细胞周期的影响。综上所述，本研究结果表明，沉默 CDC25A 可减弱 NPC 细胞的增殖并诱导细胞周期停滞，CDC25A 受 E2F1 调控。因此，CDC25A 可能是 NPC 治疗的有前途的治疗靶点。
