The impact of HnRNPF knockdown on gene expression in MDA-MB-231 cell line
Ontology highlight
ABSTRACT: We discovered that HnRNPF is significantly upregulated in breast cancer tissues and is closely associated with the cell proliferation signaling pathway. Overexpression of HnRNPF notably inhibits cell proliferation in MDA-MB-231 breast cancer cells. HnRNPF promotes the expression of the cell cycle inhibitor p21.
Project description:We discovered that USP30-AS1 is significantly upregulated in breast cancer tissues and is closely associated with the cell proliferation signaling pathway. Knockdown of USP30-AS1 notably inhibits cell proliferation in MDA-MB-231 breast cancer cells. USP30-AS1 inhibits the expression of the cell cycle inhibitor p21.
Project description:Since bone metastatic breast cancer is an incurable disease, causing significant morbidity and mortality, understanding of the underlying molecular mechanisms would be highly valuable. Here, we describe in vitro and in vivo evidence for the importance of serine biosynthesis in the metastasis of breast cancer to bone. We first characterized the bone metastatic propensity of the MDA-MB-231(SA) cell line variant as compared to the parental MDA-MB-231 cells by radiographic and histological observations in the inoculated mice. Genome-wide gene expression profiling of this isogenic cell line pair revealed that all the three genes involved in the L-serine biosynthesis pathway, phosphoglycerate dehydrogenase (PHGDH), phosphoserine aminotransferase 1 (PSAT1), and phosphoserine phosphatase (PSPH) were upregulated in the highly metastatic variant. This pathway is the primary endogenous source for L-serine in mammalian tissues. Consistently, we observed that the proliferation of MDA-MB-231(SA) cells in serine-free conditions was dependent on PSAT1 expression. In addition, we observed that L-serine is essential for the formation of bone resorbing human osteoclasts and may thus contribute to the vicious cycle of osteolytic bone metastasis. High expression of PHGDH and PSAT1 in primary breast cancer was significantly associated with decreased relapse-free and overall survival of patients and malignant phenotypic features of breast cancer. In conclusion, high expression of serine biosynthesis genes in metastatic breast cancer cells and the stimulating effect of L-serine on osteoclastogenesis and cancer cell proliferation indicate a functionally critical role for serine biosynthesis in bone metastatic breast cancer and thereby an opportunity for targeted therapeutic interventions. Parental MDA-MB-231 cells and MDA-MB-231(SA) cells were cultured in cell culture flasks. RNA was isolated in order to compare the gene expression profiles of these cell variants. Total of two samples. No replicates.
Project description:Since bone metastatic breast cancer is an incurable disease, causing significant morbidity and mortality, understanding of the underlying molecular mechanisms would be highly valuable. Here, we describe in vitro and in vivo evidence for the importance of serine biosynthesis in the metastasis of breast cancer to bone. We first characterized the bone metastatic propensity of the MDA-MB-231(SA) cell line variant as compared to the parental MDA-MB-231 cells by radiographic and histological observations in the inoculated mice. Genome-wide gene expression profiling of this isogenic cell line pair revealed that all the three genes involved in the L-serine biosynthesis pathway, phosphoglycerate dehydrogenase (PHGDH), phosphoserine aminotransferase 1 (PSAT1), and phosphoserine phosphatase (PSPH) were upregulated in the highly metastatic variant. This pathway is the primary endogenous source for L-serine in mammalian tissues. Consistently, we observed that the proliferation of MDA-MB-231(SA) cells in serine-free conditions was dependent on PSAT1 expression. In addition, we observed that L-serine is essential for the formation of bone resorbing human osteoclasts and may thus contribute to the vicious cycle of osteolytic bone metastasis. High expression of PHGDH and PSAT1 in primary breast cancer was significantly associated with decreased relapse-free and overall survival of patients and malignant phenotypic features of breast cancer. In conclusion, high expression of serine biosynthesis genes in metastatic breast cancer cells and the stimulating effect of L-serine on osteoclastogenesis and cancer cell proliferation indicate a functionally critical role for serine biosynthesis in bone metastatic breast cancer and thereby an opportunity for targeted therapeutic interventions.
Project description:The project profiled the expression patterns in hypoxia induced secretomes between MDA-MB-231 parental and MDA-MB-231 Bone Tropic (BT) breast cancer cell lines which have been previously generated by Massague and colleagues (Kang et al. Cancer Cell 2003).
Project description:P21-activated kinase 5 (PAK5) plays an important role in tumors. Yet, the connection of PAK5 with miRNA biogenesis is so far unclear.In this work, we studied the change in microRNA profiles of breast cancer MDA-MB-231 cells as a result of overexpression of PAK5 protein.
Project description:The project profiled the expression patterns in hypoxia induced secretomes between MDA-MB-231 parental and MDA-MB-231 Bone Tropic (BT) breast cancer cell lines which have been previously generated by Massague and colleagues (Kang et al. Cancer Cell 2003).
Project description:Identification of changes in protein expression by label-free shotgun proteomics in breast cancer MDA-MB-231 cells with knockdown of ELOVL5 and IGFBP6 genes in comparison with control MDA-MB-231 cells.
Project description:MDA-MB-231 breast cancer cells were infected with either Ad-GFP, Ad-FLI1, or Ad-PDEF qPCR gene expression profiling of MDA-MB-231 breast cancer cells were infected with either Ad-GFP, Ad-FLI1, or Ad-PDEF.
Project description:To determine the differentially expressed miRNAs in MDA-MB-231-GATA3 cells vs. MDA-MB-231-Control cells Pooled polyclonal cells from MDA-MB-231 breast cancer cells +/- GATA3 over-expression were analyzed for miRNA expression
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.