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Comparison of the seleno-transcriptome expression between human non-cancerous mammary epithelial cells and two human breast cancer cell lines

机译:人非癌性乳腺上皮细胞与两种人乳腺癌细胞系之间的转录组表达比较

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摘要

Breast cancer is the second most common cause of mortality in women; therefore, the identification of novel putative markers is required to improve its diagnosis and prognosis. Selenium is known to protect mammary epithelial cells from oxidative DNA damage, and to inhibit the initiation phase of carcinogenesis by stimulating DNA repair and apoptosis regulation. Consequently, the present study has focused attention on the selenoprotein family and their involvement in breast cancer. The present study performed a global analysis of the seleno-transcriptome expression in human breast cancer MCF-7 and MDA-MB231 cell lines compared with healthy breast MCF-10A cells using reverse transcription-quantitative polymerase chain reaction. The present data revealed the presence of differently expressed genes in MCF-7 and MDA-MB231 cells compared with MCF-10A cells: Four downregulated [glutathione peroxidase (GPX)1, GPX4, GPX5 and GPX7] and three upregulated (deiodinase iodothyronine, type II, GPX2 and GPX3) genes. Additionally, interactomic investigation were performed by the present study to evaluate the association between the downregulated and upregulated genes, and to identify putative HUB nodes, which represent the centers of association between the genes that are capable of direct control over the gene networks. Network analysis revealed that all differentially regulated genes, with the exception of selenoprotein T, are implicated in the same network that presents three HUB nodes interconnected to the selenoprotein mRNAs, including TP53, estrogen receptor 1 and catenin-β1 (CTNNB1). Overall, these data demonstrated for the first time, a profile of seleno-mRNAs specific for human breast cells, indicating that these genes alter their expression on the basis of the ER-positivity or negativity of breast cancer cells.
机译:乳腺癌是女性死亡的第二大最普遍原因。因此,需要鉴定新的推定标记以改善其诊断和预后。硒可保护乳腺上皮细胞免于氧化性DNA损伤,并通过刺激DNA修复和凋亡调控来抑制癌变的起始阶段。因此,本研究集中于硒蛋白家族及其在乳腺癌中的参与。本研究使用逆转录定量聚合酶链反应对健康乳腺癌MCF-10A细胞进行了人乳腺癌MCF-7和MDA-MB231细胞系中硒转录组表达的整体分析。目前的数据显示,与MCF-10A细胞相比,MCF-7和MDA-MB231细胞中存在不同表达的基因:四种下调的[谷胱甘肽过氧化物酶(GPX)1,GPX4,GPX5和GPX7]和三种上调的(去碘酶碘甲状腺素,类型II,GPX2和GPX3)基因。此外,本研究进行了相互作用组学研究,以评估下调基因和上调基因之间的关联,并确定推定的HUB节点,这些节点代表了能够直接控制基因网络的基因之间的关联中心。网络分析表明,除硒蛋白T外,所有差异调节基因均与同一网络有关,该网络呈现出三个与硒蛋白mRNA互连的HUB节点,包括TP53,雌激素受体1和连环蛋白-β1(CTNNB1)。总体而言,这些数据首次证明了对人乳腺细胞特异的硒mRNA的概况,表明这些基因基于乳腺癌细胞的ER阳性或阴性来改变其表达。

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