Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA273175 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Wound healing is a complex process that repairs organ-tissues including skin after injury. Cell migration is an important process of wound healing and fibroblast growth factor bFGF has been reported to accelerate cell migration. However, knowledge of how bFGF regulates cell migration is limited. Here, we used human foreskin fibroblast primary cells and RNA-Seq based transcriptome analysis to isolate bFGF-regulating signal pathways that regulate cell migration. Among the many pathways identified, an inflammatory response pathway was further examined for its role in fibroblast cell migration through analysis of function by the key regulator NF-κB. Application of Bay11-7082 and LPS, a typical inhibitor and inducer of inflammatory response, promoted and inhibited cell migration, respectively. Biochemical data showed that Bay11-7082 treatment induces the phosphorylation level of JNK，but PI3K inhibitor LY294002 application did not alter the IκBα phosphorylation level. In addition, Bay11-7082 and JNK inhibitor SP600125 together inhibit while LY294002 together with Bay11-7082 maintains normal cell migration, indicating that NF-κB is independent of the PI3K pathway for regulation of JNK activity during cell migration. Taken together, the present study broadens our understanding of the bFGF-regulation mechanism and further identifies a new bFGF-regulating mechanism by which NF-κB regulates JNK during human fibroblast cell migration.
2018-01-22 | GSE65193 | GEO
Project description:Cordyceps participates in various pharmacological activities including anti-tumor, and is involved in the regulation of NF-κB signaling pathway. However, the detailed role of cordycepin in suppression of NF-κB signaling pathway is less clear. In this study, we first analyzed the effect of cordyceps on NF-κB activity in TK-10 cells, and found that cordyceps resulted in a dose-dependent reduction in TNF-α-induced NF-κB activation. Here, we show that cordyceps mediated NF-kB inhibition induces apoptosis in TK-10 cells involved the serial activation of caspases. Moreover, we demonstrate that in addition to activating caspases, the cordyceps negatively modulates TNF-α-mediated NF-κB signaling to promote JNK activation, which results in apoptosis, and that NF-kB regulates antiapoptotic factor GADD45b and the JNK kinase MKK7. When the TNFα cytokine binds to the TNF receptor, IκB dissociates from NF-κB. As a result, the active NF-κB translocates to the nucleus. Cordyceps clearly prevented NF-κB from mobilizing to the nucleus, resulting in downregulation of GADD45b, whereas upregulation of MKK7 and phosphorylation of JNK (p-JNK). This increased Bax activation, leading to marked cordyceps-induced apoptosis. Bax subfamily proteins induced apoptosis through caspase-3. Furthermore, siRNA mediated inhibition of MKK7 downregulated p-JNK and The JNK inhibitor SP600125 strongly inhibited Bax. Thus, these results indicate that cordyceps inhibits NF-κB/GADD45b signaling activation to upregulate MKK7-JNK signaling pathway to induce apoptosis in TK-10 cells and support the potential of cordyceps as a therapeutic agent for renal cancer.
2016-05-24 | GSE81728 | GEO
Project description:The activated B-cell–like (ABC) subtype of diffuse large B-cell lymphoma (DLBCL) represents a very aggressive human lymphoma entity. Constitutive NF-κB activation caused by chronic active B-cell receptor (BCR) signaling is common feature of many ABC DLBCL cells; however, the pathways linking BCR signaling to the NF-κB prosurvival network are largely unknown. Here we report that constitutive activity of PI3K and the downstream kinase PDK1 are essential for the viability of two ABC DLBCL cell lines that carry mutations in the BCR proximal signaling adaptor CD79B. In these cells, PI3K inhibition reduces NF-κB activity and decreases the expression of NF-κB target genes. Furthermore, PI3K and PDK1 are required for maintaining MALT1 protease activity, which promotes survival of the affected ABC DLBCL cells. These results demonstrate a critical function of PI3K-PDK1 signaling upstream of MALT1 pro- tease and NF-κB in distinct ABC DLBCL cells and provide a rationale for the pharmacologic use of PI3K inhibitors in DLBCL therapy.
2017-02-08 | GSE94610 | GEO
Project description:Transplantation of functional neurons improve the functionally recovery in animal models of Alzheimer's disease and other neurological disorders. Although functional neurons can be differentiated from embryonic stem cells or induced-pluripotent stem cells, alternative cell sources of functional neurons may be more available for transplantation. Dedifferentiated fat cells (DFATs) were isolated and cultured from mature adipose tissue, which have advantages in their abundance, ease of isolation and homogeneity compared to other adult stem cells. DFATs are promising for clinical applications such as cell transplation therapy. Direct reprogramming has been developed in recent years. It is possible to convert mature differentiated cells into other types of functional cells by introducing cell-fate-conversion transcriptional factors. However, the introduction of exogenous transcriptional factors limits their use of clinical application. Previous studies found that in vitro neuronal differentiation follows the processes of in vivo neuronal development, which are related to the surrounding microenvironments. Therefore, the arrangement of a proper microenvironment for the neuronal development process is essential to induce neuronal differentiation. In this study, we report that DFATs differentiated into neurons by all trans retinoic acid (ATRA) and basic fibroblast growth factor (bFGF). The ATRA/bFGF-treated DFATs expressed the neuron-specific mRNA and pritein expression, exibited neuron-like morphology, generated voltage-dependent sodium current and action potentials and react with neurotransmitters. Transcriptomics resutls suggested that ATRA/bFGF treatment induced a specific differentiatioin into neurons. The lesional analysis revealed that ATRA/bFGF-treated cells are compatible with telemcephalon gabaergic neuron. To investigate the mechanism of ATRA/bFGF-induced neuronal differentiation, we performed the pathway analysis. The pathway analysis suggested that JNK signaling pathway was involved in the neuronal diffeerentiation. Our knockdown experiient further demonstrated that JNK3, a neuronal subtype of JNK, plays a crucial role in ATRA/bFGF-induced neuronal differentiation. In conclusion, we demonstrated that ATRA/bFGF induced DFATs into functional neurons via the activation of JNK3 signaling pathway. Our study provides an efficient approach for generating functional neurons from adult fat tissue and reveals the functional importance of JNK3 in neuronal differentiation process.
2020-04-17 | GSE106504 | GEO
Project description:Nuclear factor κB (NF-κB) pathway plays an important role in hepatocellular carcinoma (HCC) progression. miR-194 was previously shown to reduce the induction of NF-κB activity upon addition of tumor necrosis factor α (TNFα). To clarify the molecular mechanism responsible for the effect of miR-194 on NF-κB pathway, mRNA microarray assays were performed to identify the genes that were suppressed by miR-194. HEK-293T cells transfected with miR-194 mimics were cultured for RNA extraction and hybridization on Affymetrix mRNA microarrays. These were compared against the control, which were HEK-293T cells transfected with negative control mimics.
2015-07-01 | E-GEOD-70434 | biostudies-arrayexpress
Project description:SW480 cells overexpressing BOP1, CKS2 or NFIL3 migrated more actively compared to Control cells. Migration induced by BOP1, CKS2 or NFIL3 was repressed by interfering with distinct signaling systems using small- molecular-weight inhibitors, i.e., interference with PI3K, JNK and Notch in the case of BOP1, with PI3K and p38 MAPK in the case of CKS2, as well as with PI3K, p38 and mTOR in the case of NFIL3. Gene expression profilings suggest that BOP1, CKS2 and NFIL3 overexpression are associated functionally with a series of migration-related genes, which can be repressed transcriptionally by specific pathway inhibitors.
2015-08-04 | GSE50841 | GEO
Project description:Although therapy responsiveness to therapy in Burkitt lymphoma (BL) is high, relapsed disease and and chemoresistance remain a clinical challenge, and complete mechanisms underlying BL chemoresistance and how it can be circumvented is yet to be fully elucidated. In this study we present data showing that chymotrypsin-like serine proteases inhibitor Nα-tosyl-L-phenylalanine chloromethylketone (TPCK) and specific NF-κB inhibitor Bay-11 7082 can induce caspase-independent apoptosis in chemoresistant BL cells. We also demonstrate that both TPCK and Bay-11 7082-treatment leads to decreased NF-κB nuclear activity and that this is associated with sensitization of chemoresistant Burkitt lymphoma cells. Furthermore we investigated global transcriptional changes induced by Bay-11 7082 and TPCK in the DG-75 and Raji cell lines, respectively, by microarray analysis using Illumina BeadChips. TPCK-treatment of Raji and DG-75 cells resulted in 59 and 21 differently expressed genes, respectively, while Bay-11-treated Raji and DG-75 cells displayed 1403 and 8 differently expressed genes, respectively. Gene Ontology (GO) categorization confirmed enrichment of multiple GOs in Bay 11-treated Raji and DG-75 cells. Fifty percent of the 61 categories in Raji cells were categories sorting under Biological Processes and represented mostly increased gene expression. In DG-75 cells Bay-11 7082 induced significant gene ontology enrichment in only two categories, where the increased/decreased ratio was 1:1. Further unsupervised and supervised bioinformatics processing by Ingenuity Pathway Analysis indicated significant networks in response to TPCK and Bay 11 respectively, including association to NF-κB. Bay-11 7082 demonstrated deregulated NF-κB related members of receptor mediated cell death signaling, i.e TRAF2 and TRADD, as well as deregulated members of the NF-κB signaling pathway from the cytoplasmic compartment, i.e RELB, in Raji cells. Comparably NF-κB network analysis of Raji- and DG-75 cells treated with Bay-11 7082 and Raji cells treated with TPCK demonstrated deregulation of NF-κB target genes CD69 and IL8. These data indicates that NF-kB may play a role in overcoming chemoresistance in BL cells with defective classical apoptosis signaling. NF-κB network analysis of Raji- and DG-75 cells treated with Bay-11 7082 and Raji cells treated with TPCK
2014-01-19 | E-GEOD-31258 | biostudies-arrayexpress
Project description:SW480 cells overexpressing BOP1, CKS2 or NFIL3 migrated more actively compared to Control cells. Migration induced by BOP1, CKS2 or NFIL3 was repressed by interfering with distinct signaling systems using small- molecular-weight inhibitors, i.e., interference with PI3K, JNK and Notch in the case of BOP1, with PI3K and p38 MAPK in the case of CKS2, as well as with PI3K, p38 and mTOR in the case of NFIL3. Gene expression profilings suggest that BOP1, CKS2 and NFIL3 overexpression are associated functionally with a series of migration-related genes, which can be repressed transcriptionally by specific pathway inhibitors. SW480 stable cells were grown in DMEM, 10% FCS, and treated for 24 hr with the following inhibitors or with solvent (DMSO): SW480_Control with DMSO; SW480_BOP1 with DMSO, LY294002 (3.3 uM), SP600125 (33.3 nM) and DAPT (667 nM); SW480_CKS2 with DMSO, LY294002 (3.3 uM) and SB203580 (3.3 uM); SW480_NFIL3 with DMSO, LY294002 (3.3 uM), SB203580 (3.3 uM) and Rapamycin (33.3 nM).
2015-08-04 | E-GEOD-50841 | biostudies-arrayexpress
Project description:NF-κB has an essential role in innate immune response and inflammation and is involved in cancer development and progression. We apply the SEC-PCP-SILAC method incorporating metabolic labeling, size exclusion chromatography and protein correlation profiling to construct a complex network of interactome rearrangement in response to NF-κB modulation in breast cancer cells. Our interaction network represents a complex insight into the dynamics of MCF-7 protein interactome associated with NF-κB pathway. Our dataset could serve as a basis for future studies characterizing role of NF-κB in breast cancer cellular pathways. This PRIDE project includes results from SILAC labeled and label-free replicates from the SEC-PCP-SILAC analysis of protein complexes in MCF-7 cells with inhibited and uninhibited NF-κB pathway, results from the immunoprecipitation experiment aimed at interaction partners of NF-κB factor RELA, analysis of total proteome after NF-κB inhibition, and results from SEC fractionation of untreated and unlabeled MCF-7 cells.
2024-02-28 | PXD040125 | Pride
Project description:Background: Constitutive activation of the alternative NF-κB pathway leads to marginal zone B cell expansion and disorganized spleen microarchitecture. Furthermore, uncontrolled alternative NF-κB signaling results in the development and progression of cancer. We aimed here to learn about the mechanisms how does the constitutively active alternative NF-κB pathway exert its effects in these malignant processes. Methodology/Principal Findings: To explore the consequences of constitutive alternative NF-κB activation on genome-wide transcription, we compared gene expression profiles of wild-type and NF-kB2/p100-deficient (p100-/-) primary mouse embryonic fibroblasts (MEFs) and spleens. Microarray experiments revealed 73 differentially regulated genes in p100-/- vs. wild-type MEFs. Chromatin immunoprecipitation (ChIP) assays showed in p100-/- MEFs direct binding of RelB and p52 to the promoter of the enpp2 gene encoding Enpp2/Autotaxin, a protein with an important role in lymphocyte homing and cell migration. Gene ontology analysis revealed upregulation of genes with anti-apoptotic/proliferative activity (enpp2, serpina3g, traf1, rrad), chemotactic/locomotory activity (enpp2, ccl8), and lymphocyte homing activity (enpp2, cd34). Most importantly, biochemical analyses of MEFs and gene expression analyses of mice indicated a crosstalk between classical and alternative NF-κB pathways. Conclusions/Significance: The present results show that uncontrolled alternative NF-κB signaling is further enhanced by classical NF-κB activation, indicating that p100 deficiency alone is insufficient for full induction of a subset of genes by the alternative NF-κB pathway.
2012-12-21 | GSE30317 | GEO