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NDRG1 的上调通过影响膀胱癌中的 EMT 过程预测不良预后并促进疾病进展。

Upregulation of NDRG1 predicts poor outcome and facilitates disease progression by influencing the EMT process in bladder cancer.

机构信息

Department of Laboratory Medicine, Peking University Third Hospital, No.49 North Garden Road, Haidian District, Beijing, 100191, China.

Department of Urology, Friendship Hospital Affiliated to Capital Medical University, 95th Yong An Road, Xuan Wu District, Beijing, 100050, China.

出版信息

Sci Rep. 2019 Mar 26;9(1):5166. doi: 10.1038/s41598-019-41660-w.

Abstract

N-myc downstream regulated gene 1 (NDRG1) is an intracellular protein involved in cell differentiation and was recently reported to exert various effects in several cancers. However, its expression and role in bladder cancer remain unclear. Our study enrolled 100 bladder cancer patients to detect NDRG1 expression in tumour tissues by immunohistochemistry. Correlations between NDRG1 expression and clinical factors were analysed. An NDRG1 overexpression plasmid and NDRG1 siRNAs were transfected into bladder cancer cell lines. Cell biological behaviours were assessed by CCK-8, flow cytometry, wound healing and Transwell assays. Additionally, the influence of NDRG1 on epithelial-mesenchymal transition (EMT) was investigated by western blotting and real-time PCR. NDRG1 expression in urine from bladder cancer patients was examined by ELISA. NDRG1 protein levels were significantly increased in bladder cancer patients and correlated with tumour stage (p = 0.025), lymph node metastasis (p = 0.034) and overall survival (p = 0.016). Patients with high NDRG1 expression had poorer outcomes than those with low NDRG1 expression. NDRG1 overexpression was associated with increased cell proliferation, migration, and invasion and decreased apoptotic cell numbers; NDRG1 knockdown resulted in the inverse effects. Moreover, upregulated NDRG1 expression was associated with downregulated Cytokeratin 7 and Claudin-1 expression and upregulated N-cad, β-catenin and slug expression. Downregulated NDRG1 expression was associated with the inverse effects. Urine protein levels could distinguish bladder cancer patients from healthy controls, with an area under the curve of 0.909. NDRG1 promoted EMT in bladder cancer and could be an effective diagnostic and prognostic biomarker in bladder cancer patients.

摘要

N- 细胞癌基因下游调节基因 1(NDRG1)是一种参与细胞分化的细胞内蛋白,最近有报道称其在几种癌症中发挥多种作用。然而,其在膀胱癌中的表达和作用尚不清楚。我们的研究纳入了 100 例膀胱癌患者,通过免疫组织化学检测肿瘤组织中 NDRG1 的表达。分析了 NDRG1 表达与临床因素之间的相关性。将 NDRG1 过表达质粒和 NDRG1 siRNA 转染至膀胱癌细胞系。通过 CCK-8、流式细胞术、划痕愈合和 Transwell 实验评估细胞生物学行为。此外,通过 Western blot 和实时 PCR 研究了 NDRG1 对上皮-间质转化(EMT)的影响。通过 ELISA 检测膀胱癌患者尿液中的 NDRG1 表达。NDRG1 蛋白水平在膀胱癌患者中显著升高,与肿瘤分期(p=0.025)、淋巴结转移(p=0.034)和总生存(p=0.016)相关。NDRG1 高表达患者的预后比 NDRG1 低表达患者差。NDRG1 过表达与细胞增殖、迁移和侵袭增加以及凋亡细胞数量减少有关;NDRG1 敲低则产生相反的效果。此外,上调 NDRG1 表达与下调 Cytokeratin 7 和 Claudin-1 表达以及上调 N-cad、β-catenin 和 slug 表达有关。下调 NDRG1 表达则产生相反的效果。尿液蛋白水平可区分膀胱癌患者与健康对照者,曲线下面积为 0.909。NDRG1 促进膀胱癌 EMT,可能是膀胱癌患者有效的诊断和预后生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7616/6435802/bedec2da7afc/41598_2019_41660_Fig1_HTML.jpg

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