Similar Datasets
Project description:Investigation of Upstream-Binding Protein (UBP1) on breast cancer progression
| PRJNA1145937 | ENA
Project description:Through integrative analysis of clinical breast cancer gene expression datasets, cell line models of breast cancer progression, and mutation data from cancer genome resequencing studies, we have identified RNA binding motif protein 47 (RBM47) as a candidate suppressor of breast cancer metastasis. RBM47 inhibited breast cancer progression in experimental models. Transcriptome-wide analysis of RBM47 localization by HITS-CLIP revealed widespread binding to mRNAs, preferentially at the 3' UTRs. RBM47 altered the abundance of a subset of its target mRNAs. Some of the mRNAs stabilized by RBM47, as exemplified by dickkopf WNT signaling pathway inhibitor 1 (DKK1), mediate tumor suppressive effects downstream of RBM47. This work identifies RBM47 as a suppressor of breast cancer progression and highlights the potential of global RNA modulatory events as a source of metastasis-promoting phenotypic traits. Cancer cells transduced with doxycycline-inducible wildtype RBM47 or the RBM47-I281fs mutant, treated with increasing concentrations of doxycycline.
2014-06-11 | E-GEOD-53779 | biostudies-arrayexpress
Project description:Through integrative analysis of clinical breast cancer gene expression datasets, cell line models of breast cancer progression, and mutation data from cancer genome resequencing studies, we have identified RNA binding motif protein 47 (RBM47) as a candidate suppressor of breast cancer metastasis. RBM47 inhibited breast cancer progression in experimental models. Transcriptome-wide analysis of RBM47 localization by HITS-CLIP revealed widespread binding to mRNAs, preferentially at the 3' UTRs. RBM47 altered the abundance of a subset of its target mRNAs. Some of the mRNAs stabilized by RBM47, as exemplified by dickkopf WNT signaling pathway inhibitor 1 (DKK1), mediate tumor suppressive effects downstream of RBM47. This work identifies RBM47 as a suppressor of breast cancer progression and highlights the potential of global RNA modulatory events as a source of metastasis-promoting phenotypic traits.
2014-06-11 | GSE53779 | GEO
Project description:Low oxygen stress dynamically regulates the translation of cellular mRNAs as a means of energy conservation in seedlings of Arabidopsis thaliana. Most of the highly hypoxia-induced mRNAs are recruited to polysomes and actively translated, whereas other cellular mRNAs become translationally inactive and are either targeted for stabilization or degradation. Here we identify the involvement of OLIGOURIDYLATE BINDING PROTEIN 1 (UBP1), a triple RNA Recognition Motif protein, in dynamic and reversible aggregation of translationally repressed mRNAs during hypoxia. Mutation or downregulation of UBP1C interferes with seedling establishment and reduces survival of low oxygen stress. By use of messenger ribonucleoprotein immunopurification, we show that UBP1C constitutively binds a subpopulation of mRNAs characterized by U-rich 3’-untranslated regions under normoxic conditions. During hypoxia, UBP1C association with non-U-rich mRNAs is enhanced concomitant with its aggregation into microscopically visible cytoplasmic foci, referred to as UBP1 stress granules (SGs). This UBP1C-mRNA association occurs as global levels of protein synthesis decline. Upon reoxygenation, rapid UBP1 SG disaggregation coincides with the return of the stabilized mRNAs to polysomes. The mRNAs that are highly induced and translated during hypoxia largely circumvent UBP1C sequestration. Thus, UBP1 is established as a component of dynamically assembled cytoplasmic mRNPs that sequester mRNAs that are poorly translated during a transient low energy stress.
2014-01-13 | GSE49411 | GEO
Project description:Low oxygen stress dynamically regulates the translation of cellular mRNAs as a means of energy conservation in seedlings of Arabidopsis thaliana. Most of the highly hypoxia-induced mRNAs are recruited to polysomes and actively translated, whereas other cellular mRNAs become translationally inactive and are either targeted for stabilization or degradation. Here we identify the involvement of OLIGOURIDYLATE BINDING PROTEIN 1 (UBP1), a triple RNA Recognition Motif protein, in dynamic and reversible aggregation of translationally repressed mRNAs during hypoxia. Mutation or downregulation of UBP1C interferes with seedling establishment and reduces survival of low oxygen stress. By use of messenger ribonucleoprotein immunopurification, we show that UBP1C constitutively binds a subpopulation of mRNAs characterized by U-rich 3M-bM-^@M-^Y-untranslated regions under normoxic conditions. During hypoxia, UBP1C association with non-U-rich mRNAs is enhanced concomitant with its aggregation into microscopically visible cytoplasmic foci, referred to as UBP1 stress granules (SGs). This UBP1C-mRNA association occurs as global levels of protein synthesis decline. Upon reoxygenation, rapid UBP1 SG disaggregation coincides with the return of the stabilized mRNAs to polysomes. The mRNAs that are highly induced and translated during hypoxia largely circumvent UBP1C sequestration. Thus, UBP1 is established as a component of dynamically assembled cytoplasmic mRNPs that sequester mRNAs that are poorly translated during a transient low energy stress. Immunoprecipated RNA associated with Arabidopsis UBP1C (IP) was compared with total cellular RNA from light (L), mock dark (D), 2 h hypoxia, and 2 h hypoxia + 20 min reoxygenation treated samples with duplicate hybridizations to the Affymetrix ATH1 Genechip array.
2014-01-13 | E-GEOD-49411 | biostudies-arrayexpress
Project description:To determine the roles of RBP2 in breast cancer metastasis, MDA-MD-231 cells were transfected with siRNAs against RBP2 or luciferase control, followed with gene expression microarray analysis and gene set enrichment analysis. These analyses revealed that RBP2 knockdown significantly decreased expression of genes linked to breast cancer metastasis to lung. Total RNA obtained from the breast cancer cell line MDA-MB231 72 hours after transfection with siRNA targeting KDM5A/RBP2/JARID1A, and targeting Luceferase gene as a control.
2014-02-27 | E-GEOD-49119 | biostudies-arrayexpress
Project description:miRNAs are small non-coding RNAs frequently altered in human malignancies. They regulate protein-coding gene expression by mediating mRNA degradation and/or repressing translation via the association with the 3M-bM-^@M-^Y untranslated region (3M-bM-^@M-^Y UTR) of the mRNAs. Aberrant miRNA expression can influence several gene networks and pathways implicated in tumorigenesis and metastasis formation. To reveal miRNAs involved in breast cancer progression we investigated miRNA expression in 77 ductal breast carcinoma biopsies and 17 mammoplasties by microarray analysis. 16 differentially expressed miRNAs were identified comparing patients with or without disease relapse within 72 months from surgery. We have performed a microarray miRNA expression analysis on 77 ductal breast carcinoma biopsies and 17 normal tissues from mammoplastic reductions using the Human Agilent platform (V2). 77 frozen tumor specimens were selected from the Tumor Bank of the Department of Obstetrics and Gynecology, University of Turin. They were obtained from patients who underwent primary surgical treatment between 1988 and 2001 at a median age of 54 years (25-82). Eligibility criteria were the following: diagnosis of invasive breast cancer, all T and N stages, no distant metastasis at diagnosis (M0), complete clinical-pathological data and updated follow up. All patients were treated with radical modified mastectomy or quadrantectomy and axillary dissection plus breast irradiation. As normal breast controls 17 frozen mammoplastic reductions (EPFL, Lausanne) were included in the screening. Appropriate ethical approval was obtained for this study.
2012-12-16 | E-GEOD-26659 | biostudies-arrayexpress
Project description:To determine the roles of RBP2 in breast cancer metastasis, MDA-MD-231 cells were transfected with siRNAs against RBP2 or luciferase control, followed with gene expression microarray analysis and gene set enrichment analysis. These analyses revealed that RBP2 knockdown significantly decreased expression of genes linked to breast cancer metastasis to lung.
2014-02-27 | GSE49119 | GEO
Project description:The epithelial-to-mesenchymal transition (EMT) has been recognized as a driving force for tumor progression in breast cancer. Recently, our group identified the RNA Binding Motif Single Stranded Interacting Protein 3 (RBMS3) to be significantly associated with an EMT transcriptional program in breast cancer. Additional expression profiling demonstrated that RBMS3 was consistently upregulated by multiple EMT transcription factors and correlated with mesenchymal gene expression in breast cancer cell lines. Functionally, RBMS3 was sufficient to induce EMT in two immortalized mammary epithelial cell line. In triple-negative breast cancer (TNBC) models, RBMS3 was necessary for maintaining the mesenchymal phenotype and invasion and migration in vitro. Loss of RBMS3 significantly impaired both tumor progression and spontaneous metastasis in vivo. Using a genome-wide approach to interrogate mRNA stability, we found that ectopic expression of RBMS3 upregulates many genes that are resistant to degradation following transcriptional blockade by actinomycin D. Specifically, RBMS3 was shown to interact with the mRNA of EMT transcription factor PRRX1 and promote PRRX1 mRNA stability. PRRX1 is required for RBMS3-mediated EMT and is partially sufficient to rescue the effect of RBMS3 knockdown in TNBC cell lines. Together, this study identifies RBMS3 as a novel and common effector of EMT, which could be a promising therapeutic target for triple-negative breast cancer treatment.
2022-07-25 | GSE181237 | GEO
Project description:The primary cause of mortality in breast cancer is metastasis, a process which is still poorly understood. To study the process of breast cancer metastasis, we isolated focal hyperplasias from the MMTV-PyMT transgenic breast cancer model and transplanted to syngeneic hosts. The transplants underwent stereotyped progression to adenoma, early carcinoma, and late carcinoma at 5, 8 and 18 weeks post-transplant, respectively. We compared the gene expression profiles of adenomas and late carcinomas by microarray. Analysis of the data revealed that the most differentially expressed gene family between adenomas and late carcinomas were luminal differentiation genes, among them GATA-3. In this report, we characterized the role of GATA-3 in breast cancer. Keywords: spotted oligonucleotide Single hyperplasias were isolated from pubertal MMTV-PyMT x B-actin-GFP mice and transplanted into syngeneic hosts. Total RNA from adenomas (5 week outgrowths) were compared to late carcinomas (18 week outgrowths).
2010-07-01 | E-GEOD-5221 | biostudies-arrayexpress