Bioinformatics analysis and experimental validation reveal that CDC20 overexpression promotes bladder cancer progression and potential underlying mechanisms.

IF 1.6 4区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY
Genes & genomics Pub Date : 2024-04-01 Epub Date: 2024-03-04 DOI:10.1007/s13258-024-01505-x
Yuan Liu, Shao-Hui Zou, Xin Gao
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引用次数: 0

Abstract

Background: Bladder cancer is a prevalent malignancy. CDC20, a pivotal cell cycle regulator gene, plays a significant role in tumour cell proliferation, but its role in bladder cancer remains unclear.

Objective: This study aimed to analyse CDC20 expression in bladder cancer and explore its roles in tumour progression, treatment response, patient prognosis, and cellular proliferation mechanisms.

Methods: We systematically analysed CDC20 expression in bladder cancer using bioinformatics. Our study investigated the impact of CDC20 on chemotherapy and radiotherapy sensitivity, patient prognosis, and changes in CDC20 methylation levels. We also explored the role and potential underlying mechanisms of CDC20 in bladder cancer cell growth. We used lentiviral transfection to downregulate CDC20 expression in 5637 and T24 cells, followed by CCK-8, colony formation, scratch, invasion, apoptosis, and cell cycle analyses.

Results: CDC20 is highly expressed in bladder cancer and is significantly correlated with poor prognosis. Moreover, CDC20 demonstrated high diagnostic potential for bladder cancer (AUC > 0.9). The tumour methylation levels of CDC20 in tumour tissues markedly decreased compared with those in normal tissues, and lower methylation levels were associated with a worse prognosis. Elevated CDC20 expression is linked to increased mutation burden. Our findings suggested a potential association between high CDC20 expression and resistance to chemotherapy and radiotherapy, as CDC20 expression may impact immune cell infiltration levels. Mechanistic analysis revealed the influence of CDC20 on bladder cancer cell proliferation through cell cycle-related pathways. According to the cell experiments, CDC20 downregulation significantly impedes bladder cancer cell proliferation and invasion, leading to G1 phase arrest.

Conclusion: Aberrantly high CDC20 expression promotes tumour progression in bladder cancer, resulting in a poor prognosis, and may also constitute a promising therapeutic target.

Abstract Image

生物信息学分析和实验验证揭示了 CDC20 过表达促进膀胱癌进展及其潜在的内在机制。
背景:膀胱癌是一种常见的恶性肿瘤:膀胱癌是一种常见的恶性肿瘤。CDC20是一种关键的细胞周期调节基因,在肿瘤细胞增殖中发挥着重要作用,但其在膀胱癌中的作用仍不清楚:本研究旨在分析 CDC20 在膀胱癌中的表达,并探讨其在肿瘤进展、治疗反应、患者预后和细胞增殖机制中的作用:我们利用生物信息学系统分析了 CDC20 在膀胱癌中的表达。我们的研究调查了 CDC20 对化疗和放疗敏感性、患者预后以及 CDC20 甲基化水平变化的影响。我们还探讨了 CDC20 在膀胱癌细胞生长中的作用和潜在的内在机制。我们使用慢病毒转染技术下调了 CDC20 在 5637 和 T24 细胞中的表达,然后进行了 CCK-8、集落形成、划痕、侵袭、凋亡和细胞周期分析:结果:CDC20在膀胱癌中高表达,且与预后不良显著相关。此外,CDC20 对膀胱癌具有很高的诊断潜力(AUC > 0.9)。与正常组织相比,CDC20在肿瘤组织中的甲基化水平明显降低,而较低的甲基化水平与较差的预后有关。CDC20表达的升高与突变负荷的增加有关。我们的研究结果表明,CDC20的高表达与化疗和放疗的耐药性之间存在潜在联系,因为CDC20的表达可能会影响免疫细胞的浸润水平。机理分析表明,CDC20 通过细胞周期相关途径对膀胱癌细胞增殖产生影响。根据细胞实验,CDC20 的下调会显著阻碍膀胱癌细胞的增殖和侵袭,导致 G1 期停滞:结论:CDC20的异常高表达会促进膀胱癌的肿瘤进展,导致不良预后,也可能是一个有前景的治疗靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Genes & genomics
Genes & genomics 生物-生化与分子生物学
CiteScore
3.70
自引率
4.80%
发文量
131
审稿时长
6-12 weeks
期刊介绍: Genes & Genomics is an official journal of the Korean Genetics Society (http://kgenetics.or.kr/). Although it is an official publication of the Genetics Society of Korea, membership of the Society is not required for contributors. It is a peer-reviewed international journal publishing print (ISSN 1976-9571) and online version (E-ISSN 2092-9293). It covers all disciplines of genetics and genomics from prokaryotes to eukaryotes from fundamental heredity to molecular aspects. The articles can be reviews, research articles, and short communications.
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