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NuSAP1 的过表达预示着预后不良,并通过 Wnt/β-catenin/EMT 信号通路促进三阴性乳腺癌细胞的增殖和侵袭。

Overexpression of NuSAP1 is predictive of an unfavourable prognosis and promotes proliferation and invasion of triple-negative breast cancer cells via the Wnt/β-catenin/EMT signalling axis.

机构信息

Department of Breast Surgery, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China.

Department of Urology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China.

出版信息

Gene. 2020 Jul 15;747:144657. doi: 10.1016/j.gene.2020.144657. Epub 2020 Apr 13.

Abstract

OBJECTIVE

We analysed the effect of expression of nucleolar spindle-associated protein 1 (NuSAP1) on the prognosis of breast cancer (BC) and investigated its potential mechanism of tumourigenicity in triple-negative breast cancer (TNBC) cell lines.

MATERIALS AND METHODS

We downloaded the RNA-seq breast cancer (BC) data from The Cancer Genome Atlas (TCGA) and screened for the NuSAP1 gene using R software. The clinical data for patients with BC were screened and analysed using R software. A survival curve was drawn using the Kaplan-Meier Plotter. Cell proliferation and invasion were verified by the Cell Counting Kit-8 and Transwell assays. Expression of NuSAP1, the Wnt/β-catenin pathway, and epithelial-mesenchymal-transition-related proteins in TNBC was detected using real-time quantitative polymerase chain reaction (qRT-PCR) and western blotting (WB).

RESULTS

Expression of NuSAP1 was upregulated in BC. The change in NuSAP1 expression levels was associated with multiple clinicopathological factors, and the higher the expression of NuSAP1 was, the shorter the survival time. In MDA-MB-231 and BT549 cells, knockdown of NuSAP1 expression resulted in a significant decrease in cell proliferation and invasion; a decrease in expression of cyclin D1, vimentin, Slug, Twist, wnt3a, and pβ-catenin; and an increase in expression of e-cadherin. The results of the sh-NuSAP1 + ov-NuSPA1 group were the opposite of the results of the sh-NuSAP1 group.

CONCLUSION

NuSAP1 is a carcinogen that facilitates progression of TNBC through the Wnt/β-catenin and epithelial-mesenchymal transition pathways.

摘要

目的

我们分析核仁纺锤体相关蛋白 1(NuSAP1)的表达对乳腺癌(BC)预后的影响,并研究其在三阴性乳腺癌(TNBC)细胞系中致瘤性的潜在机制。

材料和方法

我们从癌症基因组图谱(TCGA)下载了 RNA-seq 乳腺癌(BC)数据,并使用 R 软件筛选 NuSAP1 基因。使用 R 软件筛选和分析 BC 患者的临床数据。使用 Kaplan-Meier Plotter 绘制生存曲线。通过细胞计数试剂盒-8 和 Transwell 测定验证细胞增殖和侵袭。使用实时定量聚合酶链反应(qRT-PCR)和 Western blot(WB)检测 TNBC 中 NuSAP1、Wnt/β-catenin 通路和上皮-间充质转化相关蛋白的表达。

结果

NuSAP1 在 BC 中表达上调。NuSAP1 表达水平的变化与多种临床病理因素有关,NuSAP1 表达水平越高,生存时间越短。在 MDA-MB-231 和 BT549 细胞中,敲低 NuSAP1 表达导致细胞增殖和侵袭显著减少;细胞周期蛋白 D1、波形蛋白、Slug、Twist、wnt3a 和 pβ-catenin 表达减少;E-钙黏蛋白表达增加。sh-NuSAP1+ov-NuSAP1 组的结果与 sh-NuSAP1 组的结果相反。

结论

NuSAP1 是一种致癌基因,通过 Wnt/β-catenin 和上皮-间充质转化途径促进 TNBC 的进展。

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