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

Abstract

Abstract. 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.

Current concepts and challenges to unravel the role of iodothyronine deiodinases in human neoplasias

“…Despite these negative findings, upregulation of DIO1, DIO2 and DIO3 mRNAs has been shown in MCF-7 cells. On the other hand, only DIO2 is upregulated in MDA-MB-231 when these cell lines were compared to non-tumoral human breast cells MCF-10A (Rusolo et al 2017). The differences between deiodinase mRNA expression and protein activity could be explained by different subtypes of breast tumor as well as posttranscriptional regulatory mechanisms.…”

Involvement of glutathione peroxidases in the occurrence and development of breast cancers

“…Although the active domain of GPx5 lacks selenocysteine, it retains antioxidant properties [18]. Another non-selenium glutathione peroxidase, GPx7, which lacks GPx activity, has recently been described as a novel phospholipid hydroperoxide GPx [11,[19][20][21]; the sequence of GPx7 encodes cysteine in its conserved catalytic motifs [22]. As a non-selenocysteine, GPx8 is a membrane protein that is detected in the endoplasmic reticulum, is present abundantly expressed in the lung, and was identified as a novel member of the GPx family [23].…”

“…GPx1 3p21.31 TFAP2C regulates GPx1 promoter through an AP-2 regulatory region [81] GPx1 polymorphism in modifying stress response [82] Decreased GPx1 expression [83] Loss of heterozygosity and allelic differences of GPx1 [88] Pro198Leu-associated decreased GPx1 activity with high breast cancer risk [89,92] The Leu198Leu genotype of GPx-1 [91] Regulate the sensitivity to doxorubicin [93] GPx2 14q23.3 Upregulated in breast cancer cells [19] Overexpression in rat breast cancer [98] Highly regulated by retinoic acid [94] GPx3 5q33.1 Downregulated in aggressive phenotype of breast cancer [103] An independent predictive marker for local recurrence of early-stage invasive cancer patients [104] GPx4 19p13.3 Downregulated in breast cancer cells [19] Predict poor prognosis of invasive ductal breast carcinoma [106] Impaired GPx4 expression in peripheral blood monocytes as a biomarker for increased breast cancer risk associated with an increased risk of breast cancer [91]. It is suggested that Leu carriers with the Pro198Leu GPx1 allele had a 1.9-fold increased risk of non-ductal breast cancer and a 2.6-fold increased risk of developing grade 3 ductal tumors [92].…”

Integrated Analysis to Study the Relationship between Tumor-Associated Selenoproteins: Focus on Prostate Cancer

“…Based on a transcriptomic and interactomic approach, a list of dysregulated selenoproteins was observed in two human HCC cell lines, HepG2 and Huh7, compared to normal human hepatocytes [18]. Moreover, we identified human miR-544a as able to modulate SELENOK expression in the two HepG2 and Huh7 cell lines [19], and also analyzed the selenoproteins' transcriptomes in MCF-7 and MDA-MB231 human breast cancer cell lines, compared to MCF10A normal epithelial breast cells [20]. Recently, we reported that elevated tumor tissue expression of the selenoprotein SEPHS2 in triple-negative breast cancer (TNBC) patients was correlated with the malignancy grade [21].…”