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DNA 复制和姐妹染色单体黏合 1 通过调节 Wnt/β-连环蛋白信号和 p53 蛋白促进乳腺癌的进展。

DNA replication and sister chromatid cohesion 1 promotes breast carcinoma progression by modulating the Wnt/β-catenin signaling and p53 protein.

机构信息

Department of Breast and Thyroid Surgery, Jinan Central Hospital Affiliated to Shandong First Medical University, Jinan 250013, Shandong, China.

出版信息

J Biosci. 2020;45.

PMID:33184243
Abstract

The objective of this study is to assess the prognostic and functional role of DSCC1 in breast carcinoma, as well as the potential mechanism. Based upon the TCGA data, the expression pattern and prognostic value of DSCC1 in breast carcinoma was evaluated. The mRNA and protein levels of molecules were determined using qRT-PCR and Western blot. In vitro functional role of DSCC1 in tumor cells was determined using cell counting kit 8, clone formation, and Transwell assays. Gene set enrichment analysis (GSEA) was conducted to determine DSCC1 related gene sets, which are further confirmed by Western blot. The results showed that DSCC1 is overexpressed in breast carcinoma tissues and its high expression was linked to shorter overall survival. Overexpression of DSCC1 facilitated the proliferation, invasion and migration of breast carcinoma cells, while knockdown of DSCC1 showed opposite outcomes. GSEA showed that high DSCC1 expression had a positive correlation with p53, and Wnt signaling-related molecules. Western blot showed that silencing DSCC1 increased the levels of p53 and p-β-catenin, whereas decreased p-GSK-3β and cyclin D1 expression. These observations illustrate that DSCC1 emerges a well value on the diagnosis and prognosis of breast carcinoma, and facilitates the progression of breast carcinoma partly by activating Wnt/b-catenin signaling and inhibiting p53.

摘要

本研究旨在评估 DSCC1 在乳腺癌中的预后和功能作用,以及潜在的机制。基于 TCGA 数据,评估了 DSCC1 在乳腺癌中的表达模式和预后价值。使用 qRT-PCR 和 Western blot 测定分子的 mRNA 和蛋白水平。使用细胞计数试剂盒 8、克隆形成和 Transwell 测定评估 DSCC1 在肿瘤细胞中的体外功能作用。进行基因集富集分析 (GSEA) 以确定与 DSCC1 相关的基因集,并通过 Western blot 进一步验证。结果表明,DSCC1 在乳腺癌组织中过表达,其高表达与总生存期缩短有关。DSCC1 的过表达促进了乳腺癌细胞的增殖、侵袭和迁移,而 DSCC1 的敲低则显示出相反的结果。GSEA 显示高 DSCC1 表达与 p53 和 Wnt 信号相关分子呈正相关。Western blot 显示,沉默 DSCC1 增加了 p53 和 p-β-catenin 的水平,而降低了 p-GSK-3β 和 cyclin D1 的表达。这些观察结果表明,DSCC1 在乳腺癌的诊断和预后中具有很好的价值,通过激活 Wnt/β-catenin 信号通路和抑制 p53 部分促进了乳腺癌的进展。

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