Project description:Cytoplasmic RNA bound to eIF4E was pulled down from MDA-MB-231 cells to determine the influence of radiation on eIF4E mRNA binding 4 samples were analyzed with 3 biological replicates
Project description:To identify typical enhancers and super-enhancers in the MDA-MB-231 triple-negative breast cancer cell line, we performed ChIP-seq using DNA isolated from untreated MDA-MB-231 cells using an H3K27ac antibody.
Project description:p63 ChIP-SEQ in a p63 expressing basal-subtype breast cancer cell line, MCFDCIS and in a p63 deficient claudin-low subtype breast cancer cell line, MDA-MB-231 p63 ChIP-SEQ on MCFDCIS and MDA-MB-231 cell lines
Project description:In previous studies, our research demonstrated that VNLG-152R exhibits inhibitory effects on Triple Negative Breast Cancer (TNBC) cells both in vitro and in vivo. The TNBC cell line MDA-MB-231 cells were treated with VNLG-152R. A total of 337 genes were differentially expressed when MDA-MB-231 cells were treated with 10 μM VNLG-152R for 24h; 259 genes were upregulated and 78 downregulated. Through proteome analyses, we discovered that VNLG-152R upregulates the expression of E3 ligase Synoviolin 1 (SYVN1), also called 3-hydroxy-3-methylglutaryl reductase degradation (HRD1) in TNBC cells. Moreover, we provide genetic and pharmacological evidence to demonstrate that SYVN1 mediates the ubiquitination and subsequent proteasomal degradation of MNK1/2, the only known kinases responsible for phosphorylating eIF4E. Phosphorylation of eIF4E being a rate-limiting step in the formation of the eIF4F translation initiation complex, the degradation of MNK1/2 by VNLG-152R and its analogs impedes dysregulated translation in TNBC cells, resulting in the inhibition of tumor growth. Importantly, our findings were validated in vivo using TNBC xenograft models derived from MDA-MB-231, MDA-MB-468, and MDA-MB-453 cell lines, representing different racial origins and genetic backgrounds. These xenograft models, which encompass TNBCs with varying androgen receptor (AR) expression levels, were effectively inhibited by oral administration of VNLG-152R and its deuterated analogs in NRG mice.