TNIK drives endothelial cell response to viral infection through modulating interferon signaling
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE236529 | GEO | 2024/02/09
REPOSITORIES: GEO
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Project description:SOX13 was identified as a novel flow-sensitive transceiption factor. We found that siRNA-mediated knockdown of SOX13 increased endothelial inflammatory responses even under the unidirectional laminar shear stress (ULS, mimicking s-flow) condition. To understand the underlying mechanisms, we conducted an RNAseq study in HAECs treated with SOX13 siRNA under shear conditions (ULS vs. oscillatory shear mimicking d-flow). We found 94 downregulated and 40 upregulated genes that changed in a shear- and SOX13-dependent manner. Several cytokines, including CXCL10 and CCL5, were the most strongly upregulated genes in HAECs treated with SOX13 siRNA.
2022-09-27 | GSE207087 | GEO
Project description:Atherosclerosis is a focal disease that preferentially develop in the regions of atheroprone disturbed flow, but less in regions of atheroprotective laminar flow. The mechanisms by which atheroprotective laminar flow prevents atherosclerosis at the epigenetic level remain largely unknown. In this study, we observed that laminar flow decreased histone methyltransferase EZH2, which imposes a repressive epigenetic mark of histone 3 lysine 27 trimethylation (H3K27me3) onto target gene promoters, leading to transcriptional silencing. To evaluate the effect of atheroprotective flow on EZH2 and H3K27me3 dependent genome-wide transcriptional profile, we performed RNA-sequencing study on laminar flow and EZH2 siRNA treated human endothelial cells. Venn diagram was used to compare the common regulated genes by both laminar flow and EZH2 depletion. We found atheroprotective flow and EZH2 depletion altere endothelial gene landscape, which include upregulating atheroprotective genes while downregulating pro-atherosclerotic genes.
2017-09-30 | GSE87534 | GEO
Project description:Wnt signalling maintains the undifferentiated state of intestinal crypt/progenitor cells through the TCF4/ß-catenin activating transcriptional complex. In colorectal cancer, activating mutations in Wnt pathway components lead to inappropriate activation of the TCF4/ß-catenin transcriptional program and tumourigenesis in the gut epithelium. The mechanisms by which TCF4/ß-catenin activate key target genes are not well understood. Using a proteomics approach, we identified Tnik, a member of the Germinal centre kinase family, as a Tcf4 interactor in the proliferative crypts of mouse small intestine. Tnik is recruited to promoters of Wnt target genes in mouse crypts and in Ls174T colorectal cancer cells in a ß-catenin dependent manner. Depletion of TNIK and expression of TNIK kinase mutants abrogated TCF-LEF transcription, highlighting the essential role of the kinase activity in Wnt target gene activation. siRNA depletion of TNIK followed by expression array analysis demonstrated that TNIK is an essential and exclusive activator of Wnt induced transcriptional program. As an essential component in the TCF4/ß-catenin activator complex, the kinase TNIK may present an attractive candidate for drug targeting in colorectal cancer.
2009-08-13 | GSE17623 | GEO
Project description:Purpose: The goal of this study is to compare NGS-derived transcriptome profiling (RNA-seq) of naïve/ effector (D6)/ memory (D80) p14 T cell [wild-type (WT) and Tnik-/- (KO)] isolated form spleen of naïve or adoptively transferred and LCMV-WE immunized mice. Methods: Transcriptomic profiles of splenic naïve wild-type (WT) and Tnik-/- (KO) p14 T cells (8-week-old mice) or splenic effector (D6) and memory (D80) p14 T cells (post adoptive transfer and LCMV-WE immunization) were assessed in duplicates or triplicate by deep sequencing, using Illumina HiSeq 2500. qRT–PCR validation was performed using TaqMan and SYBR Green assays. Results: We mapped about 30 million sequence reads per sample to the mouse genome (GRCm38 - mm10) and identified expressed transcripts in splenic WT and Tnik−/− p14 T cells. RNA-seq data confirmed stable expression of known housekeeping genes. Differentially expressed genes between the WT and Tnik−/− p14 T cells from naïve, D6 or D80 were identified with a fold change ≥1.5 and p-value <0.05. Hierarchical clustering and gene ontology analysis of differentially expressed genes uncovered genes that may contribute to regulation of stemness, transcriptional regulation, cell cycle regulation, survival and function of T cells. Conclusions: Our study represents the first detailed transcriptome analysis of WT versus Tnik-/- p14 T cells in the context of acute viral infection, with biologic replicates, generated by RNA-seq technology. Our results show that TNIK regulates T cell fate. Evaluation of mRNA content in effector (D6) and memory (D80) p14 T cells revealed that TNIK-deficiency during T cell activation enhances proliferation, terminal differentiation and glycolysis of effector T cells, while compromising steady-state metabolic activity of memory T cells. We conclude that TNIK imprints memory formation early after CD8+ T cell priming.
2020-02-24 | GSE127734 | GEO
Project description:Wnt signalling maintains the undifferentiated state of intestinal crypt/progenitor cells through the TCF4/Ã-catenin activating transcriptional complex. In colorectal cancer, activating mutations in Wnt pathway components lead to inappropriate activation of the TCF4/Ã-catenin transcriptional program and tumourigenesis in the gut epithelium. The mechanisms by which TCF4/Ã-catenin activate key target genes are not well understood. Using a proteomics approach, we identified Tnik, a member of the Germinal centre kinase family, as a Tcf4 interactor in the proliferative crypts of mouse small intestine. Tnik is recruited to promoters of Wnt target genes in mouse crypts and in Ls174T colorectal cancer cells in a Ã-catenin dependent manner. Depletion of TNIK and expression of TNIK kinase mutants abrogated TCF-LEF transcription, highlighting the essential role of the kinase activity in Wnt target gene activation. siRNA depletion of TNIK followed by expression array analysis demonstrated that TNIK is an essential and exclusive activator of Wnt induced transcriptional program. As an essential component in the TCF4/Ã-catenin activator complex, the kinase TNIK may present an attractive candidate for drug targeting in colorectal cancer. HEK293T cells: Wnt3A vs control medium (CM) induction for 4, 7 and 9 hours; si-TNIK vs si-control after Wnt3A induction at 4 and 7 hours (2 biological replicates for 7 hour time point); dyeswap for each experiment (i.e. 12 arrays in total).
2010-08-18 | E-GEOD-17623 | biostudies-arrayexpress
Project description:Background: The potential of expression profiling using microarray analysis as a tool to predict the prognosis for different types of cancer has been realized. This study aimed to identify a novel biomarker for colorectal cancer (CRC). Methods: The expression profiles of cancer cells in 152 patients with stage I-III CRC were examined using microarray analysis. High expression in CRC cells, especially in patients with distant recurrences, was a prerequisite to select candidate genes. Thus, we identified eleven candidate genes, and selected Traf2- and Nck-interacting kinase (TNIK), which was known to be associated with progression in CRC through Wnt signaling pathways. We analyzed the protein expression of TNIK using immunohistochemistry (IHC) and investigated the relationship between protein expression and patient characteristics in 220 stage I-III CRC patients. Results: Relapse-free survival was significantly worse in the TNIK high expression group than in the TNIK low expression group in stage II (p = 0.028) and stage III (p = 0.006) patients. In multivariate analysis, high TNIK expression was identified as a significant independent risk factor of distant recurrence in stage III patients. Conclusion: This study is the first to demonstrate the prognostic significance of intratumoral TNIK protein expression in clinical tissue samples of CRC, in that high expression of TNIK protein in primary tumors was associated with distant recurrence in stage II and III CRC patients. This TNIK IHC study might contribute to practical decision-making in the treatment of these patients.
2016-07-22 | GSE71222 | GEO
Project description:Hippocampi from adult TNIK-/- and TNIK+/+ mice were dissected out, the mRNA extracted, and hybridized to arrays. The aim was to determine the extent and nature of differential expression in the mutant, particularly those changes which might be indicative of major physiological changes.
2012-10-10 | E-MTAB-1202 | biostudies-arrayexpress
Project description:This study investigates the role of endothelial cell (EC) gene expression in the focal origin of atherosclerosis, particularly in response to local hemodynamics. Differential gene expression was profiled in EC isolated from athero-susceptible and athero-protected regions of the normal pig aorta. Specifically, a region of disturbed flow (DF, the inner aortic arch) was compared to a region of undisturbed flow (UF, descending thoracic aorta). Linearly amplified RNA was used to screen nylon filter arrays of 13,824 human cDNAs.
2006-07-21 | E-CBIL-17 | biostudies-arrayexpress
Project description:We performed bulk RNA-seq on primary and immortalized human renal proximal tubule epithelial cells (RPTECs) subjected to siRNA mediated TNIK silencing.
2024-04-10 | GSE216015 | GEO
Project description:Background: The potential of expression profiling using microarray analysis as a tool to predict the prognosis for different types of cancer has been realized. This study aimed to identify a novel biomarker for colorectal cancer (CRC). Methods: The expression profiles of cancer cells in 152 patients with stage I-III CRC were examined using microarray analysis. High expression in CRC cells, especially in patients with distant recurrences, was a prerequisite to select candidate genes. Thus, we identified eleven candidate genes, and selected Traf2- and Nck-interacting kinase (TNIK), which was known to be associated with progression in CRC through Wnt signaling pathways. We analyzed the protein expression of TNIK using immunohistochemistry (IHC) and investigated the relationship between protein expression and patient characteristics in 220 stage I-III CRC patients. Results: Relapse-free survival was significantly worse in the TNIK high expression group than in the TNIK low expression group in stage II (p = 0.028) and stage III (p = 0.006) patients. In multivariate analysis, high TNIK expression was identified as a significant independent risk factor of distant recurrence in stage III patients. Conclusion: This study is the first to demonstrate the prognostic significance of intratumoral TNIK protein expression in clinical tissue samples of CRC, in that high expression of TNIK protein in primary tumors was associated with distant recurrence in stage II and III CRC patients. This TNIK IHC study might contribute to practical decision-making in the treatment of these patients. Gene expression profiles for 152 cancer tissues from colorectal cancer patients were measured by Affymetrix HG-U133 Plus 2.0 arrays. Normalization was performed by robust multi-array average (RMA) method under R 2.12.1 statistical software with affy package from BioConductor. The normalized gene expression levels were presented as log2-transformed values by RMA.
2016-07-22 | E-GEOD-71222 | biostudies-arrayexpress