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Differential epigenetic profiles induced by sodium selenite in breast cancer cells
Affiliation:1. School of Public Health, Sun Yat-sen University, Guangzhou 510080, China;2. The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China;3. The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou 510630, China;1. Department of Orthopaedics, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, 362000, PR China;2. Department of Neurology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, 362000, PR China;1. DCFQE/ Faculty of Sciences and Technology, University of the Azores, 9501-855 Ponta Delgada, Azores, Portugal;2. Cardiology Department, Hospital Divino Espírito Santo de Ponta Delgada-EPER, Avenida D. Manuel, 9500-782 Ponta Delgada, Azores, Portugal;1. Department of Medical Oncology, Jiangsu Cancer Hospital, Nanjing Medical University, No. 42 Baiziting Road, Nanjing 210009, China;2. Department of Medical Oncology, First People’s Hospital of Yunnan Province, No. 175 Jinbi Road, Kunming 650032, China
Abstract:ObjectivesSelenium (Se) was a potential anticancer micronutrient with proposed epigenetic effect. However, the Se-induced epigenome in breast cancer cells was yet to be studied.MethodsThe profiles of DNA methylation, microRNA (miRNA), long non-coding RNA (lncRNA), and message RNA (mRNA) in breast cancer cells treated with sodium selenite were examined by microarrays. We verified the epigenetic modifications by integrating their predicted target genes and differentially expressed mRNAs. The epigenetically regulated genes were further validated in a breast cancer cohort by associating with tumor progression. We conducted a series of bioinformatics analyses to assess the biological function of these validated genes and identified the critical genes.ResultsThe Se-induced epigenome regulated the expression of 959 genes, and 349 of them were further validated in the breast cancer cohort. Biological function analyses suggested that these validated genes were enriched in several cancer-related pathways, such as PI3K/Akt and metabolic pathways. Based on the degrees of expression change, hazard ratio difference, and connectivity, NEDD4L and FMO5 were identified as the critical genes.ConclusionsThese results confirmed the epigenetic effects of sodium selenite and revealed the epigenetic profiles in breast cancer cells, which would help understand the mechanisms of Se against breast cancer.
Keywords:Selenium  Epigenome  Breast cancer
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