关键词: Bladder cancer CDC20 Cell cycle Prognosis Proliferation Therapeutic target

Mesh : Humans Cell Line, Tumor Urinary Bladder Neoplasms / metabolism Cell Proliferation / genetics Cell Cycle / genetics Cell Cycle Proteins / genetics Computational Biology Cdc20 Proteins / genetics metabolism

来  源:   DOI:10.1007/s13258-024-01505-x

Abstract:
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.
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.
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.
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.
Aberrantly high CDC20 expression promotes tumour progression in bladder cancer, resulting in a poor prognosis, and may also constitute a promising therapeutic target.
摘要:
背景:膀胱癌是一种普遍的恶性肿瘤。CDC20,一个关键的细胞周期调节基因,在肿瘤细胞增殖中起重要作用,但其在膀胱癌中的作用尚不清楚。
目的:本研究旨在分析膀胱癌中CDC20的表达,并探讨其在肿瘤进展中的作用,治疗反应,患者预后,和细胞增殖机制。
方法:我们使用生物信息学系统分析了膀胱癌中CDC20的表达。我们的研究调查了CDC20对化疗和放疗敏感性的影响,患者预后,和CDC20甲基化水平的变化。我们还探讨了CDC20在膀胱癌细胞生长中的作用和潜在的潜在机制。我们使用慢病毒转染下调5637和T24细胞中的CDC20表达,其次是CCK-8,集落形成,划痕,入侵,凋亡,和细胞周期分析。
结果:CDC20在膀胱癌中高表达,与不良预后显著相关。此外,CDC20显示出对膀胱癌的高诊断潜力(AUC>0.9)。与正常组织相比,肿瘤组织中CDC20的肿瘤甲基化水平明显下降,较低的甲基化水平与较差的预后相关。CDC20表达升高与突变负荷增加有关。我们的研究结果表明,高CDC20表达与化疗和放疗耐药之间存在潜在关联。CDC20表达可能影响免疫细胞浸润水平。机制分析显示CDC20通过细胞周期相关通路对膀胱癌细胞增殖的影响。根据细胞实验,CDC20下调显著阻碍膀胱癌细胞增殖和侵袭,导致G1期停滞。
结论:CDC20异常高表达促进膀胱癌肿瘤进展,导致预后不良,并且也可能构成有希望的治疗靶标。
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