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Published on: January 16, 2015
Identification of epigenetic modifications mediating the antagonistic effect of selenium against cadmium-induced
Zhuo-Zhi Liang1, Yi-Xin Zhang1, Rui-Mei Zhu1,2
1School of Public Health, Sun Yat-Sen University, Guangzhou, 510080, China.
Abstract:
The antagonistic effect of selenium (Se) against cadmium (Cd)-induced breast carcinogenesis was reported, but underlying mechanisms were unclear. The aim of this study was to identify the epigenetically regulated genes and biological pathways mediating the antagonistic effect. We exposed MCF-7 cells to Cd and Se alone or simultaneously. Cell proliferation was assessed by MTT assay, and differential epigenome (DNA methylation, microRNA, and long non-coding RNA) was obtained by microarrays. We cross-verified the epigenetic markers with differential transcriptome, and the ones modulated by Cd and Se in opposite directions were regarded to mediate the antagonistic effect. The epigenetically regulated genes were validated by using gene expression data in human breast tissues. We further assessed the biological functions of these validated genes. Our results showed that Se alleviated the proliferative effect of Cd on MCF-7 cell. A total of 10 epigenetically regulated genes were regarded to mediate the antagonistic effect, including APBA2, KIAA0895, DHX35, CPEB3, SVIL, MYLK, ZFYVE28, ABLIM2, GRB10, and PCDH9. Biological function analyses suggested that these epigenetically regulated genes were involved in multiple cancer-related pathways, such as focal adhesion and PI3K/Akt pathway. In conclusion, we provided evidence that Se antagonized the Cd-induced breast carcinogenesis via epigenetic modification and revealed the critical pathways.
Insights
Selenium (Se) counteracts cadmium (Cd)-induced breast cancer by altering gene expression. This study identified 10 key genes and pathways involved in selenium
Area of Science:
- Environmental Toxicology
- Cancer Epigenetics
- Molecular Biology
Background:
- Cadmium (Cd) exposure is linked to breast cancer.
- Selenium (Se) shows antagonistic effects against Cd-induced carcinogenesis.
- Mechanisms underlying Se's protective role remain largely unknown.
Purpose of the Study:
- To elucidate the epigenetic mechanisms behind Se's antagonism to Cd.
- To identify specific epigenetically regulated genes and pathways involved.
Main Methods:
- MCF-7 cells were treated with Cd and Se.
- Cell proliferation was measured using MTT assay.
- Epigenomic profiling (DNA methylation, miRNA, lncRNA) and transcriptomic analysis were performed.
- Cross-verification of epigenetic markers with transcriptomic data identified key genes.
Main Results:
- Selenium alleviated the proliferative effects of cadmium on MCF-7 cells.
- Ten epigenetically regulated genes (e.g., APBA2, CPEB3, MYLK) were identified as mediators.
- These genes are implicated in cancer-related pathways like focal adhesion and PI3K/Akt signaling.
Conclusions:
- Selenium antagonizes Cd-induced breast carcinogenesis through epigenetic modifications.
- Identified genes and pathways provide novel insights into Se's chemopreventive potential.
- This study highlights the role of epigenetics in environmental carcinogenesis and prevention.
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