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- W3211035402 abstract "Genome-wide association studies (GWAS) have identified more than 2000 single nucleotide polymorphisms (SNPs) associated with breast cancer susceptibility, most of which are located in the non-coding region. However, the causal SNPs functioning as gene regulatory elements still remain largely undisclosed. Here, we applied a Dinucleotide Parallel Reporter sequencing (DiR-seq) assay to evaluate 288 breast cancer risk SNPs in nine different breast cancer cell lines. Further multi-omics analysis with the ATAC-seq (Assay for Transposase-Accessible Chromatin using sequencing), DNase-seq (DNase I hypersensitive sites sequencing) and histone modification ChIP-seq (Chromatin Immunoprecipitation sequencing) nominated seven functional SNPs in breast cancer cells. Functional investigations show that rs4808611 affects breast cancer progression by altering the gene expression of NR2F6. For the other site, rs2236007, the alteration promotes the binding of the suppressive transcription factor EGR1 and results in the downregulation of PAX9 expression. The downregulated expression of PAX9 causes cancer malignancies and is associated with the poor prognosis of breast cancer patients. Our findings contribute to defining the functional risk SNPs and the related genes for breast cancer risk prediction." @default.
- W3211035402 created "2021-11-08" @default.
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- W3211035402 date "2021-10-26" @default.
- W3211035402 modified "2023-10-15" @default.
- W3211035402 title "Functional Screenings Identify Regulatory Variants Associated with Breast Cancer Susceptibility" @default.
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- W3211035402 doi "https://doi.org/10.3390/cimb43030124" @default.
- W3211035402 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/34889888" @default.
- W3211035402 hasPublicationYear "2021" @default.
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