Similar Datasets
Project description:SNHG12 knockdown in Human Umbilical Vein Cells under ROS conditions.
| PRJNA575048 | ENA
Project description:It is generally believed that vascular endothelial cells (VECs) rely on glycolysis instead of the tricarboxylic acid (TCA) cycle under both normoxic and hypoxic conditions. However, the metabolic pattern of human umbilical vein endothelial cells (HUVECs) under extreme ischemia (hypoxia and nutrient deprivation) needs to be elucidated. We initiated a lethal ischemic model of HUVECs, performed proteomics and bioinformatics, and verified the metabolic pattern shift of HUVECs. Ischemic HUVECs displayed extensive aerobic respiration, including upregulation of the TCA cycle and mitochondrial respiratory chain in mitochondria and downregulation of glycolysis in cytoplasm. The TCA cycle was enhanced while the cell viability was decreased through the citrate synthase pathway when substrates of the TCA cycle (acetate and/or pyruvate) were added and vice versa when inhibitors of the TCA cycle (palmitoyl-CoA and/or avidin) were applied. The inconsistency of the TCA cycle level and cell viability suggested that the extensive TCA cycle can keep cells alive yet generate toxic substances that reduce cell viability. The data revealed that HUVECs depend on "ischemic TCA cycle" instead of glycolysis to keep cells alive under lethal ischemic conditions, but consideration must be given to relieve cell injury.
| S-EPMC9552233 | biostudies-literature
Project description:BackgroundThe balance between endothelial cell survival and apoptosis during stress is an important cellular process for vessel integrity and vascular homeostasis, and it is also pivotal in angiogenesis during the development of many vascular diseases. However, the underlying molecular mechanisms remain largely unknown. Although both transcription and alternative splicing are important in regulating gene expression in endothelial cells under stress, the regulatory mechanisms underlying this state and their interactions have not yet been studied on a genome-wide basis.ResultsHuman umbilical vein endothelial cells (HUVECs) were treated with cobalt chloride (CoCl2) both to mimic hypoxia and to induce cell apoptosis and alternative splicing responses. Cell apoptosis rate analysis indicated that HUVECs exposed to 300 microM CoCl2 for 24 hrs were initially counterbalancing apoptosis with cell survival. We therefore used the Affymetrix exon array system to determine genome-wide transcript- and exon-level differential expression. Other than 1583 differentially expressed transcripts, 342 alternatively spliced exons were detected and classified by different splicing types. Sixteen alternatively spliced exons were validated by RT-PCR. Furthermore, direct evidence for the ongoing balance between HUVEC survival and apoptosis was provided by Gene Ontology (GO) and protein function, as well as protein domain and pathway enrichment analyses of the differentially expressed transcripts. Importantly, a novel molecular module, in which the heat shock protein (HSP) families play a significant role, was found to be activated under mimicked hypoxia conditions. In addition, 46% of the transcripts containing stress-modulated exons were differentially expressed, indicating the possibility of combinatorial regulation of transcription and splicing.ConclusionThe exon array system effectively profiles gene expression and splicing on the genome-wide scale. Based on this approach, our data suggest that transcription and splicing not only regulate gene expression, but also carry out combinational regulation of the balance between survival and apoptosis of HUVECs under mimicked hypoxia conditions. Since cell survival following the apoptotic challenge is pivotal in angiogenesis during the development of many vascular diseases, our results may advance the knowledge of multilevel gene regulation in endothelial cells under physiological and pathological conditions.
| S-EPMC2678155 | biostudies-literature
Project description:Tissue factor (TF) has been extensively studied for tumor metastasis, but its role in mediating cancer cell adhesion to vasculature remains unknown. This study aimed to measure the ability of TF to mediate the adhesion of breast cancer cells to human umbilical vein endothelial cells (HUVECs). MDA-MB-231 cells expressed the highest TF level and adhered more to HUVECs under static and flow conditions, a neutralizing TF antibody abolished the enhanced adhesion of MDA-MB-231 cells to HUVECs. Recombinant human soluble TF (rTF) bonded β1integrin on HUVECs surfaces, β1 or α3integrin antibody combined with TF antibody abolished more cell-cell adhesion. These data suggested that TF mediated adhesion of breast cancer cells to endothelial cells may rely on β1integrin on HUVECs surfaces.
| S-EPMC7993123 | biostudies-literature
Project description:The high glucose?induced activation of protein kinase C??2 (PKC??2) has an essential role in the pathophysiology of diabetes?associated vascular disease. In the present study, human umbilical vein endothelial cells (HUVECs) were cultured in high and normal glucose conditions prior to being infected with a recombinant adenovirus to induce the overexpression of PKC??2. The activity of PKC??2 was also decreased using a selective PKC??2 inhibitor. A series of two?dimensional electrophoresis images detected ~800 spots in the nuclei, and ~600 spots in the cytosol. Following intra? and inter?group cross?matching, 38 significantly altered spots were identified as high glucose?induced and PKC??2?associated nuclear proteins. In addition to the observation that the regulation of key proteins involved in the nuclear factor (NF)??B signaling cascade occurred in the cytosol, various transcription factors, including peroxisome proliferator?activated receptor ? (PPAR??), were also altered in the nuclei. A human protein?protein interaction network of potential connections of PKC??2?associated proteins was constructed in the proteomics investigation using Biological General Repository for Interaction Datasets. The results indicated that PKC??2 may be involved in high glucose?induced glucose and lipid crosstalk by regulating PPAR??. In addition, NF??B inhibitor?interacting Ras?like protein 1 may be important in the PKC??2?NF??B inhibitor?NF??B signaling pathway in HUVECs under high?glucose conditions.
| S-EPMC4626174 | biostudies-literature
Project description:Genetic and epigenetic changes contribute to intratumor heterogeneity and chemotherapy resistance in several tumor types. LncRNAs have been implicated, directly or indirectly, in the epigenetic regulation of gene expression. We investigated lncRNAs that potentially mediate carboplatin-resistance of cell subpopulations, influencing the progression of ovarian cancer (OC). Four carboplatin-sensitive OC cell lines (IGROV1, OVCAR3, OVCAR4, and OVCAR5), their derivative resistant cells, and two inherently carboplatin-resistant cell lines (OVCAR8 and Ovc316) were subjected to RNA-sequencing and global DNA methylation analysis. Integrative and cross-validation analyses were performed using external (The Cancer Genome Atlas, TCGA dataset, n=111 OC samples) and internal datasets (n=39 OC samples) to identify lncRNA candidates. A total of 4,255 differentially expressed genes (DEGs) and 14,529 differentially methylated CpG positions (DMPs) were identified comparing sensitive and resistant OC cell lines. The comparison of DEGs between OC cell lines and TCGA-OC dataset revealed 570 genes, including 50 lncRNAs, associated with carboplatin resistance. Eleven lncRNAs showed DMPs, including the SNHG12. Knockdown of SNHG12 in Ovc316 and OVCAR8 cells increased their sensitivity to carboplatin. The results suggest that the lncRNA SNHG12 contributes to carboplatin resistance in OC and is a potential therapeutic target. We demonstrated that SNHG12 is functionally related to epigenetic mechanisms.
2022-04-20 | GSE198073 | GEO
Project description:Genetic and epigenetic changes contribute to intratumor heterogeneity and chemotherapy resistance in several tumor types. LncRNAs have been implicated, directly or indirectly, in the epigenetic regulation of gene expression. We investigated lncRNAs that potentially mediate carboplatin-resistance of cell subpopulations, influencing the progression of ovarian cancer (OC). Four carboplatin-sensitive OC cell lines (IGROV1, OVCAR3, OVCAR4, and OVCAR5), their derivative resistant cells, and two inherently carboplatin-resistant cell lines (OVCAR8 and Ovc316) were subjected to RNA-sequencing and global DNA methylation analysis. Integrative and cross-validation analyses were performed using external (The Cancer Genome Atlas, TCGA dataset, n=111 OC samples) and internal datasets (n=39 OC samples) to identify lncRNA candidates. A total of 4,255 differentially expressed genes (DEGs) and 14,529 differentially methylated CpG positions (DMPs) were identified comparing sensitive and resistant OC cell lines. The comparison of DEGs between OC cell lines and TCGA-OC dataset revealed 570 genes, including 50 lncRNAs, associated with carboplatin resistance. Eleven lncRNAs showed DMPs, including the SNHG12. Knockdown of SNHG12 in Ovc316 and OVCAR8 cells increased their sensitivity to carboplatin. The results suggest that the lncRNA SNHG12 contributes to carboplatin resistance in OC and is a potential therapeutic target. We demonstrated that SNHG12 is functionally related to epigenetic mechanisms.
2022-04-20 | GSE198042 | GEO
Project description:To investigate the differentially expressed lncRNAs,CircRNAs and mRNAs in Human Umbilical Vein Endothelial Cells between normal pregnancy and preeclampsia, we performed the human lncRNA,cirRNA and mRNA microarray analysis of 8 samples from clinical patients.
2021-05-12 | GSE165324 | GEO
Project description:BackgroundFoetal anaemia and umbilical vein thrombosis are rare pregnancy complications that can increase the risk of perinatal adverse events, which, in severe cases, can lead to foetal death. During pregnancy, umbilical vein varix (UVV) commonly occurs in the intra-abdominal part of the umbilical vein and is associated with an increased risk of foetal anaemia and umbilical vein thrombosis. However, UVV occurring in the extra-abdominal part of the umbilical vein is rare, especially when accompanied by thrombosis. In this case report, we describe a rare case of an extensive extra-abdominal umbilical vein varix (EAUVV), which ultimately resulted in foetal death due to umbilical vein thrombosis.Case presentationIn this report, we describe a rare case of an extensive EAUVV that was discovered at 25 weeks and 3 days of gestation. During the examination, there were no abnormalities in foetal haemodynamics. The estimated weight of the foetus was only 709 g. In addition to refusing to be hospitalized, the patient refused close monitoring of the foetus. As a result, we were limited to choosing an expectant therapy. The foetus died 2 weeks after diagnosis and was confirmed to have EAUVV with thrombosis after the induction of labour.ConclusionIn the case of EAUVV, lesions are extremely rare, and it is very easy for thrombosis to form, which may result in the death of the child. When determining the next step in the treatment of the condition, the degree of UVV, possible complications, gestational age, foetal haemodynamics, and other relevant factors are strongly connected to the clinical therapy decision, and these factors should be considered comprehensively when making a clinical decision. We recommend close monitoring with hospital admission (to facilities capable of handling extremely preterm foetuses) after variability in delivery for worsening haemodynamic status.
| S-EPMC9993576 | biostudies-literature
Project description:HUVECs of ischemia for 3 h, ischemia for 3 h/reperfusion for 24 h, and control group for 3 h were collected to identify respiratory and metabolic status under lethal ischemic condition. The results showed that HUVECs depend on ischemic TCA cycle rather than glycolysis to keep cells alive under lethal ischemia condition.
2023-03-11 | PXD031313 | Pride