| Autor: |
Tracy KM; Department of Biochemistry, University of Vermont Larner College of Medicine, Burlington, VT 05405., Prior S; Department of Biomedical and Health Sciences, University of Vermont College of Nursing and Health Sciences, Burlington, VT 05405., Trowbridge WT; Department of Biochemistry, University of Vermont Larner College of Medicine, Burlington, VT 05405., Boyd JR; Department of Biomedical and Health Sciences, University of Vermont College of Nursing and Health Sciences, Burlington, VT 05405., Ghule PN; Department of Biochemistry, University of Vermont Larner College of Medicine, Burlington, VT 05405; Department of Biomedical and Health Sciences, University of Vermont College of Nursing and Health Sciences, Burlington, VT 05405., Frietze S; Department of Biochemistry, University of Vermont Larner College of Medicine, Burlington, VT 05405; Department of Biomedical and Health Sciences, University of Vermont College of Nursing and Health Sciences, Burlington, VT 05405; University of Vermont Cancer Center, University of Vermont Larner College of Medicine, Burlington, VT 05405., Stein JL; Department of Biochemistry, University of Vermont Larner College of Medicine, Burlington, VT 05405; University of Vermont Cancer Center, University of Vermont Larner College of Medicine, Burlington, VT 05405., Stein GS; Department of Biochemistry, University of Vermont Larner College of Medicine, Burlington, VT 05405; University of Vermont Cancer Center, University of Vermont Larner College of Medicine, Burlington, VT 05405., Lian JB; Department of Biochemistry, University of Vermont Larner College of Medicine, Burlington, VT 05405; University of Vermont Cancer Center, University of Vermont Larner College of Medicine, Burlington, VT 05405. |
| Abstrakt: |
Long non-coding RNA (lncRNA)-mediated control of gene expression contributes to regulation of biological processes that include proliferation and phenotype, as well as compromised expression of genes that are functionally linked to cancer initiation and tumor progression. lncRNAs have emerged as novel targets and biomarkers in breast cancer. We have shown that mitotically associated lncRNA MANCR is expressed in triple-negative breast cancer (TNBC) cells and that it serves a critical role in promoting genome stability and survival in aggressive breast cancer cells. Using an siRNA strategy, we selectively depleted BRD2, BRD3, and BRD4, singly and in combination, to establish which bromodomain proteins regulate MANCR expression in TNBC cells. Our findings were confirmed by using in situ hybridization combined with immunofluorescence analysis that revealed BRD4, either alone or with BRD2 and BRD3, can support MANCR regulation of TNBC cells. Here we provide evidence for MANCR-responsive epigenetic control of super enhancers by histone modifications that are required for gene transcription to support cell survival and expression of the epithelial tumor phenotype in triple negative breast cancer cells. |
