Abstract Breast cancer is one of the most common malignant tumors in women. Derlin-1 has been found to be overexpressed in several human cancers in addition to playing an important role in tumor processes; however, the expression patterns and functions of Derlin-1 in human breast cancer are not fully understood. In this study, we found that Derlin-1 overexpression was higher in breast cancer compared to normal samples through TCGA and GTEx database analyses. Kaplan-Meier plotter analysis showed that Derlin-1 was a predicting factor for patient prognosis. Derlin-1 expression was significantly up-regulated in breast cancer tissues (18/30, 60.00%) compared to corresponding paracancerous tissue (9/30, 30.00%, p < 0.05) as detected by immunohistochemistry, and the expression of Derlin-1 was correlated to pathological grading. siRNA interference of Derlin-1 inhibited cell proliferation, which is associated with the promotion of apoptosis and migration. Derlin-1 knockdown suppressed the protein levels of p-AKT and Cyclin D1 while up-regulating Caspase3 and Bax. GEPIA database analysis showed that MTDH and ATAD2 were downstream target genes, and the expression of MTDH and was suppressed in Derlin-1 knockdown cells. Taken together, our results demonstrated ATAD2 that Derlin-1 is overexpressed in breast cancer and promoted a malignant phenotype through the AKT signaling pathway.

中文翻译：

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Derlin-1 在乳腺癌中作为生长促进剂

摘要 乳腺癌是女性最常见的恶性肿瘤之一。除了在肿瘤过程中发挥重要作用外，还发现 Derlin-1 在几种人类癌症中过度表达；然而，Derlin-1 在人乳腺癌中的表达模式和功能尚不完全清楚。在本研究中，我们通过 TCGA 和 GTEx 数据库分析发现，与正常样本相比，乳腺癌中的 Derlin-1 过表达更高。Kaplan-Meier 绘图仪分析表明，Derlin-1 是患者预后的预测因素。与免疫组织化学检测到的相应癌旁组织（9/30, 30.00%, p < 0.05）相比，乳腺癌组织中的 Derlin-1 表达显着上调（18/30, 60.00%），并且 Derlin-1 的表达与病理分级相关。Derlin-1 的 siRNA 干扰抑制细胞增殖，这与促进细胞凋亡和迁移有关。Derlin-1 敲低抑制了 p-AKT 和细胞周期蛋白 D1 的蛋白质水平，同时上调了 Caspase3 和 Bax。GEPIA数据库分析显示MTDH和ATAD2是下游靶基因，在Derlin-1敲低细胞中MTDH和ATAD2的表达受到抑制。总之，我们的结果表明 ATAD2，即 Derlin-1 在乳腺癌中过度表达并通过 AKT 信号通路促进恶性表型。和 MTDH 的表达在 Derlin-1 敲低细胞中被抑制。总之，我们的结果表明 ATAD2，即 Derlin-1 在乳腺癌中过度表达并通过 AKT 信号通路促进恶性表型。和 MTDH 的表达在 Derlin-1 敲低细胞中被抑制。总之，我们的结果表明 ATAD2，即 Derlin-1 在乳腺癌中过度表达并通过 AKT 信号通路促进恶性表型。