Integrative Bioinformatics and Functional Analyses of GEO, ENCODE, and TCGA Reveal FADD as a Direct Target of the Tumor Suppressor BRCA1
Abstract
:1. Introduction
2. Results
2.1. Identification of Potential BRCA1 Target Genes from ENCODE, GEO, and TCGA Data Analysis
2.2. BRCA1 Overexpression Positively Regulates FADD, MEIS2, and CKS1B Expression
2.3. BRCA1 Knockdown Negatively Regulates FADD, MEIS2, and CKS1B Expression
2.4. BRCA1 Activates the Promoter Region of FADD but Not the Other Target Genes
2.5. Fas Ligand (FasL) Signaling and BRCA1 Expression Reduce Proliferation
2.6. Low Expression of FADD is Correlated with Poor Survival of Triple-Negative Breast Cancer (TNBC) Patients, Whereas the Opposite Occurs in Estrogen Receptor (ER)-Positive Cases
3. Discussion
4. Materials and Methods
4.1. GEO, ENCODE, and TCGA Data Analysis
4.2. ChIP Assay
4.3. DNA Constructs
4.4. Transfection and Luciferase Assay
4.5. Knockdown Using siRNA
4.6. Real-Time PCR Analysis
4.7. Western Blot Analysis
4.8. AlamarBlue® Cell Proliferation Assay
4.9. PROgeneV2 Analysis
4.10. Statistical Analysis
Supplementary Materials
Author Contributions
Acknowledgments
Conflicts of Interest
References
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Gene Name | Function | ENCODE Data (CHIP seq) a | BRCA1 KD/Ctr b | BRCA1 overExp/Ctr c | TCGA Correlation d |
---|---|---|---|---|---|
CKS1B | binding to the catalytic subunit of the cyclin-dependent kinases and is essential for their biological function | −319 | 0.66 | 1.90 | 0.29 |
FADD | an adaptor molecule that interacts with various cell surface receptors and mediates cell apoptotic signals | +152 | 1.06 | 2.10 | 0.24 |
MEIS2 | binding to HOX or PBX proteins to form dimers, or to a DNA-bound dimer of these proteins and is thought to play a role in stabilization of the homeoprotein-DNA complex for transcriptional regulation | +521,171 | 0.77 | 1.01 | −0.32 |
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Nguyen, D.-D.; Lee, D.G.; Kim, S.; Kang, K.; Rhee, J.-k.; Chang, S. Integrative Bioinformatics and Functional Analyses of GEO, ENCODE, and TCGA Reveal FADD as a Direct Target of the Tumor Suppressor BRCA1. Int. J. Mol. Sci. 2018, 19, 1458. https://doi.org/10.3390/ijms19051458
Nguyen D-D, Lee DG, Kim S, Kang K, Rhee J-k, Chang S. Integrative Bioinformatics and Functional Analyses of GEO, ENCODE, and TCGA Reveal FADD as a Direct Target of the Tumor Suppressor BRCA1. International Journal of Molecular Sciences. 2018; 19(5):1458. https://doi.org/10.3390/ijms19051458
Chicago/Turabian StyleNguyen, Dinh-Duc, Dong Gyu Lee, Sinae Kim, Keunsoo Kang, Je-keun Rhee, and Suhwan Chang. 2018. "Integrative Bioinformatics and Functional Analyses of GEO, ENCODE, and TCGA Reveal FADD as a Direct Target of the Tumor Suppressor BRCA1" International Journal of Molecular Sciences 19, no. 5: 1458. https://doi.org/10.3390/ijms19051458