Genome-wide analysis of gene expression in MDA-MB-231 breast cancer cells in response to conditional miRNA mediated OPN knockdown
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE133608 | GEO | 2019/11/04
REPOSITORIES: GEO
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Project description:Our goal was to identify the genes, which are modulated following conditional BSP knockdown for 3 and 6 days. Thus, to elucidate the BSP relevance and to broaden the knowledge on the affected signalling pathways.
2014-02-28 | GSE55432 | GEO
Project description:Our goal was to identify the genes, which are modulated following conditional BSP knockdown for 3 and 6 days. Thus, to elucidate the BSP relevance and to broaden the knowledge on the affected signalling pathways. Cell pellets were collected after 3 and 6 days of cultivating the cells in media with or without doxycycline. There were duplicated total RNA samples for each time interval and each condition.The mRNA expression of the in vitro miRNA treated cells was compared to the respective +dox control.
2014-02-28 | E-GEOD-55432 | biostudies-arrayexpress
Project description:BackgroundPrevious studies showed that suppression of pyruvate carboxylase (PC) expression in highly invasive breast cancer cell line, MDA-MB-231 inhibits cell growth as a consequence of the impaired cellular biosynthesis. However, the precise cellular mechanism underlying this growth restriction is unknown.MethodsWe generated the PC knockdown (PCKD) MDA-MB-231 cells and assessed their phenotypic changes by fluorescence microscopy, proliferation, apoptotic, cell cycle assays and proteomics.ResultsPC knockdown MDA-MB-231 cells had a low percentage of cell viability in association with accumulation of abnormal cells with large or multi-nuclei. Flow cytometric analysis of annexin V-7-AAD positive cells showed that depletion of PC expression triggers apoptosis with the highest rate at day 4. The increased rate of apoptosis is consistent with increased cleavage of procaspase 3 and poly (ADP-Ribose) polymerase. Cell cycle analysis showed that the apoptotic cell death was associated with G2/M arrest, in parallel with marked reduction of cyclin B levels. Proteomic analysis of PCKD cells identified 9 proteins whose expression changes were correlated with the degree of apoptosis and G2/M cell cycle arrest in the PCKD cells. STITCH analysis indicated 3 of 9 candidate proteins, CCT3, CABIN1 and HECTD3, that form interactions with apoptotic and cell cycle signaling networks linking to PC via MgATP.ConclusionsSuppression of PC in MDA-MB-231 cells induces G2/M arrest, leading to apoptosis. Proteomic analysis supports the potential involvement of PC expression in the aberrant cell cycle and apoptosis, and identifies candidate proteins responsible for the PC-mediated cell cycle arrest and apoptosis in breast cancer cells.General significanceOur results highlight the possibility of the use of PC as an anti-cancer drug target.
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Project description:BackgroundEarlier, we have identified PTOV1 as a novel interactome of PIN1 in PC-3 cells. This study aims to explore the functional similarity and the common role of both genes in breast cancer cell proliferation.MethodsCTG, crystal violet assay, clonogenic assay, wound healing assay, cell cycle analysis, Hoechst staining and ROS measurement were performed to assess cell viability, colony forming potential, cell cycle arrest, nuclear condensation and ROS production after knocking down of PTOV1 and PIN1 by siRNAs in MDA-MB-231 and MCF-7 cells. CO-IP, qPCR and western blot were performedto study interaction, transcriptional and translational regulation of both genes.ResultsKnockdown of PTOV1 and PIN1 inhibited the cell proliferation, colony formation, migration, cell cycle, and induced nuclear condensation as well as ROS production. Interaction of PTOV1 and PIN1 was validated by Co-IP in MDA-MB-231 cells. Genes involved in cell proliferation, migration, cell cycle, and apoptosis were regulated by PIN1 and PTOV1. PTOV1 knockdown inhibited Bcl-2, Bcl-xL and inducedBAX, LC3 and Beclin-1expression. Overexpression of PIN1 increased the expression of PTOV1. Knockdown of both genes inhibited the expression of cyclin D1, c-Myc, and β-catenin.ConclusionsPTOV1 and PIN1 interact and exert oncogenic role in MDA-MB-231 cells by sharing the similar expression profile at transcriptional and translational level which can be a promising hub for therapeutic target.
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Project description:CD44, an adhesion molecule that binds to extracellular matrix, primarily to hyaluronan (HA), has been implicated in cancer cell migration, invasion, and metastasis. CD44 has also recently been recognized as a marker for stem cells of several types of cancer. However, the roles of CD44 in the development of bone metastasis still remain unclear. To explore this issue, we established the MDA-MB-231 human breast cancer cells stably expressing short hairpin RNA against CD44. The CD44-knockdown MDA-MB-231 cells (MDA-MB-231 shCD44-2 and shCD44-3) were analyzed. As control, MDA-MB-231 cells stably expressing shRNA against firefly luciferase (shLuc) were used. Total of three samples. No replicates.
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Project description:Our goal was to identify the genes, which are modulated following conditional BSP knockdown for 3 and 6 days. Thus, to elucidate the BSP relevance and to broaden the knowledge on the affected signalling pathways. Cell pellets were collected after 3 and 6 days of cultivating the cells in media with or without doxycycline. There were duplicated total RNA samples for each time interval and each condition.The mRNA expression of the in vitro miRNA treated cells was compared to the respective +dox control.
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Project description:Breast cancer is one of the most common malignant cancers among women and a major clinical obstacle. Although studies have reported the abnormal expression of SIRT7 in breast cancer, whether the function of SIRT7 regulates the expression of long noncoding RNAs (lncRNAs) in breast cancer remains unknown. We aimed to determine the differential expressions of mRNAs and lncRNAs associated with SIRT7 and understand the regulatory mechanism of SIRT7 in breast cancer. RNA sequencing was performed to explore the transcriptome in MDA-MB-231 cells after SIRT7 depletion, and a total of 50,634 different transcripts were identified. In comparison with the negative control, siSIRT7 groups showed 240 differentially expressed mRNAs and 26 differentially expressed lncRNAs. Gene ontology analysis revealed that the differentially expressed mRNAs mainly regulated DNA replication, CXCR chemokine receptor binding, and maturation of large subunit rRNA from tricistronic rRNA transcript, nucleoplasm, mitochondrion, and NAD+ ADP-ribosyltransferase activity. Kyoto Encyclopedia of Genes and Genomes analysis showed that the differentially expressed mRNAs were mainly involved in pathways associated with MAPK signaling pathway, tumor necrosis factor signaling pathway, hepatitis B, and cancer. Moreover, the target genes of the differentially expressed lncRNAs mainly regulated the carboxylic acid metabolic processes and were involved in glycolysis pathway. The mRNA-lncRNA coexpression network comprised 186 mRNAs and 23 lncRNAs. Our results provide essential data regarding differentially expressed lncRNAs and mRNAs after the depletion of SIRT7 in breast cancer cells, which may be useful to elucidate the role of SIRT7 in breast cancer development.
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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.
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Project description:We recently showed that inactivation of the WASF3/WAVE3 gene in breast cancer cells results in loss of cell motility and invasion in vitro and metastasis in vivo. To obtain a better understanding of molecular mechanisms of action of WASF3, we have established the stable WASF3 knockdown MDA-MB-231 cells using shRNA strategy. We used microarrays to detail the global programme of gene expression after silencing WASF3 and identified distinct classes of up or down-regulated genes associated with breast cancer cell migration and motility The three stable WASF3 knockdown single clones and three control clones were selected for RNA extraction and hybridization on Affymetrix microarrays. To identify altered gene expression patterns in the knockdown cells, we compared gene expression levels between three different knockdown and three different control clones.
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Project description:In the past decades, altered Follistatin‑like 1 (FSTL1) expression has been documented in a variety of cancers, while its functional roles are poorly understood. Particularly in breast cancer, the expression of FSTL1 and its signaling pathway remain to be determined. In the present study, an elevated FSTL1 expression and a supressed cell proliferation were detected in a specific brain metastatic cell line MDA‑MB‑231‑BR (231‑BR), compared with its parental cell line MDA‑MB‑231. However, this protein was hardly detected in the other three breast cancer cell lines. Next, lentiviral vectors encoding FSTL1 or FSTL1 specific shRNAs were used to overexpress or knock down FSTL1 in MDA‑MB‑231 or 231‑BR, respectively (MDA‑MB‑231FSTL1 or 231‑BRsh FSTL1). Results showed that overexpression of FSTL1 inhibited MDA‑MB‑231 cell proliferation, while knockdown of FSTL1 in 231‑BR cells promotes cell proliferation, compared with their corresponding control groups. These results were further confirmed in nude mouse xenografts. The tumor volume in 231‑BR cell-bearing mice was significantly smaller than that of MDA‑MB‑231 group, and reduction of tumor volume was detected in MDA‑MB‑231FSTL1 cell-bearing mice compared with the control group. Previous studies revealed that TGF‑β-Smad2/3 signaling pathway was activated in 231‑BR and MDA‑MB‑231FSTL1 cells, which may contribute to the inhibited cell proliferation. In addition, Smad3 knockdown could restore the inhibition of cell proliferation induced by FSTL1 overexpression in MDA‑MB‑231FSTL1 cells, indicating that the anti‑proliferative effect of FSTL1 overexpression may be associated with Smad3 involved TGF‑β signaling pathway regulation. This study identified FSTL1 as an inhibitor of cell proliferation in MDA‑MB‑231 and 231‑BR cell lines, which may provide new insights into the development and management of breast cancer.
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