Monocyte membrane-coated nanoparticles (MoNP)-Verteporfin (VP) treatment alleviated the TNFalpha-induced inflammatory response in Endothelial cells
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE229918 | GEO | 2024/10/23
REPOSITORIES: GEO
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Project description:Verteporfin (VP) inhibts colon cancer growth in vivo and in cell lines by inducing high molecular weight oligomerization of proteins. The antitumor effect of VP is independent of its YAP inhibitor activity. Tumor hypoxia contributes partly to antitumor effect of VP by impairing clearance of VP-induced high molecular weight aggregates.
2015-10-14 | PXD002793 | Pride
Project description:Verteporfin (trade name Visudyne) is a medication used as a photosensitizer for photodynamic therapy to eliminate the abnormal blood vessels in the eye associated with conditions such as the wet form of macular degeneration. Verteporfin accumulates in these abnormal blood vessels and, when stimulated by nonthermal red light with a wavelength of 689 nm[1] in the presence of oxygen, produces highly reactive short-lived singlet oxygen and other reactive oxygen radicals, resulting in local damage to the endothelium and blockage of the vessels. Recently, it was reported that VP has chemotherapeutic effect in cancer. To identify the gene expression profile in gastric cancer cells by VP, we performed microarray.
2017-12-26 | GSE77982 | GEO
Project description:Purpose: The goals of this study are to compare VEGF-treated HUVECs with or without Verteporfin (VP) pretreatment transcriptome profiling (RNA-seq) to microarray and quantitative reverse transcription polymerase chain reaction (qRT–PCR) methods and to evaluate protocols for optimal high-throughput data analysis Methods: After serum-starving for 12 hours, HUVECs were divided into two group: VEGF and VEGF+VP. Cells from VEGF+VP group were pretreated with VP (4 μM) for 2 hours and then all cells were treated with VEGF (200 ng/mL) for another 24 hours. Subsequently, total RNA from HUVECs were prepared using Trizol reagent and mRNA library was constructed. RNA-sequencing: RNA-sequencing was carried out by BGI (Beijing Genomic Institute, ShenZhen, China). SOAPnuke software (v1.5.2) was used to filter the data for RNA-sequencing and then these data were mapped to the reference genome using HISAT2 software (v2.0.4). The clean reads were aligned to the gene set by Bowtie2 (v2.2.5). The expression level of genes was then measured by RSEM software (v1.2.12). The heatmap of top 40 different expression genes was drawn according to the gene expression with FPKM (fragment per kilobase of transcript per million). Reactome (https://www.reactome.org/) enrichment analysis of different expression genes was undertaken and the significant levels of terms and pathways were corrected by Q value. Results: The statistical results of significant DEGS confirmed that approximately 7204 genes of the transcripts showed differential expression between the VEGF group and VEGF+VP group, with a fold change ≥1.5 and p value <0.05. Altered expression of 20 genes was confirmed with qRT–PCR, demonstrating the high degree of sensitivity of the RNA-seq method. Hierarchical clustering of differentially expressed genes uncovered several as yet uncharacterized genes that may contribute to angiogenesis. Data analysis with GO analysis and GSEA analysis revealed a significant overlap yet provided complementary insights in transcriptome profiling. Conclusions: Our study represents the first detailed transcriptomic analysis of VEGF treated HUVECs with or without VP treatment, with biologic replicates, generated by RNA-seq technology. The optimized data analysis workflows reported here should provide a framework for comparative investigations of expression profiles.
2022-04-06 | GSE181880 | GEO
Project description:Abstract Hippo pathway downstream effectors Yap and Taz play key roles in cell proliferation and regeneration, regulating gene expression especially via interaction with Tead transcription factors. To investigate their role in skeletal muscle stem cells, we analysed Taz in vivo and ex vivo in comparison to Yap. Taz was expressed in activated satellite cells. siRNA knockdown or constitutive expression of wildtype or constitutively active TAZ mutants showed that TAZ promoted proliferation, a function that was shared with YAP. However, at later stages of myogenesis, TAZ also enhanced myogenic differentiation of myoblasts, whereas YAP inhibits such differentiation. Functionally, while muscle growth was mildly affected in Taz (gene symbol Wwtr1-/-) knockout mice, there were no overt effect on regeneration. However, conditional knockout of Yap in satellite cells of Pax7Cre-ERT2/+ : Yapflox/flox : Rosa26Lacz mice produced a marked regeneration deficit. To identify potential mechanisms, microarray analysis showed many common Taz/Yap targets, but Taz also regulates some genes independently of Yap, including myogenic genes such as Pax7, Myf5 and Myod1. Proteomic analysis of Yap/Taz revealed many common binding partners, but Taz also interacts with proteins distinct from Yap, that are mainly involved in myogenesis and aspects of cytoskeleton organization. Neither TAZ nor YAP bind members of the Wnt destruction complex but both extensively changed expression of Wnt and Wnt-cross talking genes with known roles in myogenesis. Finally, TAZ operates through Tead4 to enhance myogenic differentiation. In summary, Taz and Yap have overlapping functions in promoting myoblast proliferation but Taz then switches to promote myogenic differentiation.
2017-06-13 | PXD005751 | Pride
Project description:Uncontrolled Transforming growth factor-beta (TGFβ) signaling promotes aggressive metastatic properties in late-stage breast cancers. However, how TGFβ-mediated cues are directed to induce late-stage tumorigenic events is poorly understood, particularly given that TGFβ has clear tumor suppressing activity in other contexts. Here we demonstrate that the transcriptional regulators TAZ and YAP (TAZ/YAP), key effectors of the Hippo pathway, are necessary to promote and maintain TGFβ-induced tumorigenic phenotypes in breast cancer cells. Interactions between TAZ/YAP, TGFβ-activated SMAD2/3, and TEAD transcription factors reveal convergent roles for these factors in the nucleus. Genome-wide expression analyses indicate that TAZ/YAP, TEADs and TGFβ-induced signals coordinate a specific pro-tumorigenic transcriptional program. Importantly, genes cooperatively regulated by TAZ/YAP, TEAD, and TGFβ, such as the novel targets NEGR1 and UCA1, are necessary for maintaining tumorigenic activity in metastatic breast cancer cells. Nuclear TAZ/YAP also cooperate with TGFβ signaling to promote phenotypic and transcriptional changes in non-tumorigenic cells to overcome TGFβ repressive effects. Our work thus identifies crosstalk between nuclear TAZ/YAP and TGFβ signaling in breast cancer cells, revealing novel insight into late-stage disease-driving mechanisms. Expression profiling was conducted following the repression of the transcriptional regulators TAZ and YAP (TAZ/YAP), the TEAD family of transcription factors (TEAD1/2/3/4), or the TGFb signaling pathway (with SB-431542, an inhibitor of the TBRI recpeptor) in human MDA-MB-231-LM2 breast cancer cells treated with TGFβ1. Human MDA-MB-231-LM2-4 breast cancer cells were transfected with control siRNA, or siRNAs targeting TAZ/YAP or all four TEADs and were treated 24 hours later with 500pM TGFβ1 or 5mM SB-431542 for an additional 24 hours. Total RNA was isolated and twelve microarrays in total were performed, with each condition carried out three times on separate days. The Boston University Microarray Core generated the data using the Affymetrix Human Gene 1.0 St Array.
2014-04-02 | E-GEOD-56445 | biostudies-arrayexpress
Project description:Together with TEAD4 the Hippo pathway effector YAP stimulates chromosomal instability. Verteporfin is known to disrupt the physical YAP/TEAD interaction and tehrefore might prevent from chromosomal instability in liver cancer. Immortalized HCC cell line hepG2 is treated with Verteporfin for 24 hours.
2016-02-11 | E-GEOD-73396 | biostudies-arrayexpress
Project description:Purpose: It has been observed that the drug verteporfin (VP), a known disruptor of YAP-TEAD signaling, causes cell rounding and changes in phenotype and biosynthesis in human nucleus pulposus cells. In this study the time-dependent effects of VP treatment on the transcriptome of human NP cells was explored. Methods: mRNA profiles of NP cells treated for 24 hours, 48 hours, or 4 days with VP or vehicle (DMSO) control were generated for cells from 3 adult human tissue samples, using Illumina NovaSeq. Unaligned reads were trimmed based on quality score (minimum quality level (Phred) = 20, minimum read length = 25) and aligned to the whole human genome (STAR 2.6.1d; hg19) using Partek Flow software. This software suite was also used to calculate the counts/normalized counts of genes and to perform gene specific analysis (GSA), principle component analysis (PCA), hierarchical clustering, and gene set enrichment. Differentially regulated genes were considered to be those with a fold change value (VP/DMSO) for a given time point that was greater than or equal to 2 or less than or equal to negative 2 and a FDR-adjusted p-value of less than or equal to 0.05. Results: Using a data analysis workflow buit in Partek Flow, we identified 1810 differentially regulated genes at 24 hours, 4287 differentially regulated genes at 48 hours, and 9272 differentially regulated genes at 4 days. Hierarchical clustering and PCA analysis demonstrated clustering of the data by patient and time point, but separation by treatment group. We further observed that while generally the expression of fibroblastic markers decreased with VP treatment, a number of markers of NP phenotype were increased. We also identified enriched gene sets (ex. 2026 at the 4 day time point) which represented a variety of cellular components, processes, and functions potentially implicated by VP treatment. Conclusions: The data from this RNA-sequencing demonstrate that VP treatment which induces cell rounding in NP cells was also accompanied by pronounced and time-dependent changes in the transcriptome of adult NP cells in culture. The enriched gene sets and differentially regulated genes suggest a major role for cell adhesion, cytoskeletal remodeling, vacuolar lumen, and M APK activity in the NP phenotypic and functional response to changes in cell shape.
2020-08-03 | GSE151090 | GEO
Project description:We conditionally knocked out both Yap and Taz in cranial neural crest (CNC) using the Wnt1Cre driver and sequenced mRNA from embryonic day 10.5 mandibles. Examination of mRNA level in E10.5 mandibular tissues from control and Wnt1Cre Taz and Yap dKO mutant.
2016-03-01 | E-GEOD-69311 | biostudies-arrayexpress
Project description:Oral squamous cell carcinoma (OSCC) is a prevalent form of cancer that develops from the epithelium of the oral cavity. OSCC is on the rise worldwide, and death rates associated with the disease are particularly high. Despite progress in understanding of the mutational and expression landscape associated with OSCC, advances in deciphering these alterations for the development of therapeutic strategies have been limited. Further insight into the molecular cues that contribute to OSCC is therefore required. Here we show that the transcriptional regulators YAP (YAP1) and TAZ (WWTR1), which are key effectors of the Hippo pathway, drive pro-tumorigenic signals in OSCC. Regions of pre-malignant oral tissues exhibit aberrant nuclear YAP accumulation, suggesting that dysregulated YAP activity contributes to the onset of OSCC. Supporting this premise, we determined that nuclear YAP and TAZ activity drives OSCC cell proliferation, survival, and migration in vitro, and is required for OSCC tumor growth and metastasis in vivo. Global gene expression profiles associated with YAP and TAZ knockdown revealed changes in the control of gene expression implicated in pro-tumorigenic signaling, including those required for cell cycle progression and survival. Notably, the transcriptional signature regulated by YAP and TAZ significantly correlates with gene expression changes occurring in human OSCCs identified by The Cancer Genome Atlas (TCGA), emphasizing a central role for YAP and TAZ in OSCC biology. Expression profiling was conducted following the repression of the transcriptional regulators TAZ and YAP (YAP/TAZ) in human SCC2 oral cancer cells. Human SCC2 oral cancer cells were transfected with control siRNA, or siRNAs targeting TAZ, YAP, or YAP/TAZ for 48 hours. Total RNA from three independent experiments carried out on separate days was isolated and purified and the samples were then profiled on Affymetrix Human Gene 2.0 Chips at the Boston University Microarray Core. The expression profiles were processed and normalized using the Robust Multi-array Average (RMA) procedure (23) based on a custom Brainarray CDF (24). For each of the siRNA experiments, signatures of genes differentially expressed between treatment and corresponding siRNA control with an FDR q-value ?0.05 and a fold change ?2 were identified as either activated (up-regulated in control) or repressed (up-regulated in treatment). The overlap between the differentially expressed gene signatures was evaluated by Fisher test. Hierarchical gene and sample clustering was performed on the top 3000 genes with highest median absolute deviation (MAD; a robust version of the variance) across 12 samples, using “ward” as the agglomeration rule, and 1 minus Pearson correlation and Euclidean as the distance measures for genes and samples, respectively.
2015-05-26 | E-GEOD-66949 | biostudies-arrayexpress
Project description:The Hippo pathway downstream effectors, Yap and Taz, play key roles in cell proliferation and tissue growth, regulating gene expression especially via interaction with Tead transcription factors. To investigate their role in skeletal muscle stem cells, we analysed gene expression changes driven by Taz and compared these to Yap mediated changes to the transcriptome by measurement of gene expression on Affymetrix microarrays. To interrogate overlapping and unique transcriptional changes driven by these Hippo effectors, satellite cell-derived myoblasts were transduced with constitutively active TAZ S89A or YAP S127A retrovirus for 24h or 48h, with empty retrovirus as control. Triplicate microarray analyses of empty vector controls, hYAP1 S127A and TAZ S89A transgenic primary myoblasts were conducted.
2017-06-20 | E-MTAB-5395 | biostudies-arrayexpress