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神经前体细胞表达,发育下调 8 促进膀胱癌的肿瘤进展并预测患者的预后不良。

Neural precursor cell expressed, developmentally downregulated 8 promotes tumor progression and predicts poor prognosis of patients with bladder cancer.

机构信息

Department of Urology, The Second Hospital of Tianjin Medical University, Tianjin, China.

Sino-Singapore Eco-City Hospital of Tianjin Medical University, Tianjin, China.

出版信息

Cancer Sci. 2019 Jan;110(1):458-467. doi: 10.1111/cas.13865. Epub 2018 Dec 10.

Abstract

Neddylation has been researched in many different human carcinomas. However, the roles of neural precursor cell expressed, developmentally downregulated 8 (NEDD8) in bladder cancer are still unknown. Our study was the first study which systematically investigated the possible functions of NEDD8 in bladder cancer (BC) progression. We carried out immunohistochemistry to explore associations between the expression of NEDD8 in tumor tissues and clinical outcomes of patients. RT-qPCR and western blot were used to detect the expressional levels of genes. The biological abilities of cell proliferation, migration and invasion were researched by in vitro and in vivo experiments. Results were as follows: Data from The Cancer Genome Atlas (TCGA) database showed that NEDD8 was overexpressed in BC tissues and was associated with poor patient survival. Results of immunohistochemistry found that NEDD8 was significantly associated with poor clinical outcomes of BC patients. Suppression of NEDD8 could inhibit the proliferation, migration and invasion of tumor cells. Knocking down NEDD8 could induce apoptosis and G2 phase arrest of cell cycle progression. In vivo, suppression of NEDD8 restricted growth and metastasis of tumors in mice. In conclusion, NEDD8 has important roles in regulating the progression of BC cells and was associated with poor prognosis of patients; hence, it may become a potential therapeutic target of BC.

摘要

Neddylation 在许多不同的人类癌中进行了研究。然而,神经前体细胞表达的、发育下调的 8 号(NEDD8)在膀胱癌中的作用仍不清楚。我们的研究是首次系统研究 NEDD8 在膀胱癌(BC)进展中的可能作用的研究。我们进行了免疫组织化学研究,以探索肿瘤组织中 NEDD8 的表达与患者临床结局之间的关联。通过 RT-qPCR 和 Western blot 检测基因的表达水平。通过体外和体内实验研究细胞增殖、迁移和侵袭的生物学能力。结果如下:来自癌症基因组图谱(TCGA)数据库的数据显示,NEDD8 在 BC 组织中过表达,与患者生存不良相关。免疫组织化学结果发现,NEDD8 与 BC 患者的不良临床结局显著相关。抑制 NEDD8 可抑制肿瘤细胞的增殖、迁移和侵袭。敲低 NEDD8 可诱导细胞周期进程中的细胞凋亡和 G2 期阻滞。在体内,抑制 NEDD8 可限制小鼠肿瘤的生长和转移。总之,NEDD8 在调节 BC 细胞的进展中起重要作用,并与患者的不良预后相关;因此,它可能成为 BC 的潜在治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cfaf/6317957/31142d504c1b/CAS-110-458-g001.jpg

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