To identify intrinsic mechanismis that mediating Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) resistance , gene expression analysis was performed on MDA-MB-231 cell lines exposed to TRAIL, in parental (Sensitive) or treat to resistance (TTR) conditions.
A Genome-Wide Loss-of-Function Screen Identifies SLC26A2 as a Novel Mediator of TRAIL Resistance.
Cell line
View SamplesMacrophage inflammatory protein 1alpha/CCL3 protein is a known pro-inflammatory cytokine that can mediate chemotaxis of monocytes and promote cell degranulation. Ccl3 gene expression is elevated in the CNS and visceral tissue of many lysosomal storage disorders. The deletion of Ccl3 in a mouse model of Sandhoff disease was reported to result in reduced monocyte-associated pathology in the brain, delayed neurodegeneration, and prolonged health. However, deletion of Ccl3 in a mouse model of Niemann-Pick C disease was dentrimental or neutral instead of beneficial. Prevention of neuronal loss was instead mediated by providing NPC1 to neurons.
Neuronal and epithelial cell rescue resolves chronic systemic inflammation in the lipid storage disorder Niemann-Pick C.
Specimen part
View SamplesWe undertook a survey of gene expression changes in primary microglial cultures with and without neurovirulent (FrCasE) and non-neurovirulent (Fr57E) virus infection to identify physiological changes that could be relevant to the induction of spongiform neurodegeneration. These gene expression analyses were performed using Affymetrix 430A mouse GeneChips (5 chips for each of the three experimental conditions, representing over 14,000 murine genes and ESTs. RNA from 5 separate microglial culture preparations were analyzed for Control (mock infected), Fr57E-, and FrCasE-infected microglia. Present/absent calls were based on MicroArray Suite 5.0 from Affymetrix. Affymetrix CEL files were analyzed using dChip software after normalization of the data between all 15 arrays. Statistical analyses were performed using ANOVA.
Gene expression profiling of microglia infected by a highly neurovirulent murine leukemia virus: implications for neuropathogenesis.
Specimen part
View SamplesExpression analysis of 36 pancreatic ductal adenocarcinoma tumors and matching normal pancreatic tissue samples from pancreatic cancer patients of the Clinical Institute Fundeni (ICF) using Affymetrix U133 Plus 2.0 whole-genome chips.
Combined gene expression analysis of whole-tissue and microdissected pancreatic ductal adenocarcinoma identifies genes specifically overexpressed in tumor epithelia.
Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Screening and validation of lncRNAs and circRNAs as miRNA sponges.
Cell line
View SamplesIntensive research in past two decades has uncovered the presence and importance of noncoding RNAs (ncRNAs), which includes microRNAs (miRs) and long ncRNAs (lncRNAs). These two classes of ncRNAs interact to a certain extent, as some lncRNAs bind to miRs to sequester them. Such lncRNAs are collectively called 'competing endogenous RNAs' or 'miRNA sponges'. In this study, we screened for lncRNAs that may act as miRNA sponges using the publicly available data sets and databases. To uncover the roles of miRNA sponges, loss-of-function experiments were conducted, which revealed the biological roles as miRNA sponges. LINC00324 is important for the cell survival by binding to miR-615-5p leading to the de-repression of its target BTG2 LOC400043 controls several biological functions via sequestering miR-28-3p and miR-96-5p, thereby changing the expressions of transcriptional regulators. Finally, we also screened for circular RNAs (circRNAs) that may function as miRNA sponges. The results were negative at least for the selected circRNAs in this study. In conclusion, miRNA sponges can be identified by applying a series of bioinformatics techniques and validated with biological experiments.
Screening and validation of lncRNAs and circRNAs as miRNA sponges.
Cell line
View SamplesNC1153 was shown to inhibit JAK3 tyrosine kinase. Lymphocytes survival depends on the integrity of STAT5, the primary downstream target of JAK3.
Uncoupling JAK3 activation induces apoptosis in human lymphoid cancer cells via regulating critical survival pathways.
Cell line
View SamplesIn most metazoan nuclei, heterochromatin is located at the nuclear periphery in contact with the nuclear lamina, which provides mechanical stability to the nucleus. We show that in cultured cells, chromatin de-compaction by the nucleosome binding protein HMGN5 decreases the sturdiness, elasticity, and rigidity of the nucleus. Mice overexpressing HMGN5, either globally or only in the heart, are normal at birth but develop hypertrophic heart with large cardiomyoctyes, deformed nuclei and disrupted lamina, and die of cardiac malfunction. Chromatin de-compaction is seen in cardiomyocytes of newborn mice but misshaped nuclei with disrupted lamina are seen only in adult cardiomyocytes, suggesting that loss of heterochromatin diminishes the ability of the nucleus to withstand the mechanical forces of the contracting heart. Thus, heterochromatin enhances the ability of the nuclear lamina to maintain the sturdiness and shape of the eukaryotic nucleus; a structural role for chromatin that is distinct from its genetic functions.
Chromatin decompaction by the nucleosomal binding protein HMGN5 impairs nuclear sturdiness.
Specimen part
View SamplesIn order to provide functional data of kidney-specific long intergenic non-coding RNAs (lincRNA), loss-of-function study was conducted.
Logic programming to infer complex RNA expression patterns from RNA-seq data.
Cell line
View SamplesUnderstanding the mechanisms of host macrophage responses to Mycobacterium tuberculosis (M.tb.) is essential for uncovering potential avenues of intervention to boost host resistance to infection. Macrophage transcriptome profiling revealed M.tb. infection strongly induced expression of several enzymes controlling tryptophan (Trp) catabolism. This included indole 2,3-dioxygenase 1 (IDO1) and tryptophan 2,3-dioxygenase (TDO2), which catalyze the rate-limiting step in the kynurenine pathway, producing ligands for the aryl hydrocarbon receptor (AHR). The AHR and heterodimeric partners AHR nuclear translocator (ARNT) and RELB are robustly expressed, and AHR and RELB levels further increased during infection. Infection enhanced AHR/ARNT and AHR/RELB DNA binding, and stimulated expression of AHR target genes, including that encoding the inflammatory cytokine IL1beta. AHR target gene expression was further enhanced by exogenous kynurenine, and exogenous Trp, kynurenine or synthetic agonist indirubin reduced mycobacterial viability. Comparative expression profiling revealed that AHR ablation diminished expression of numerous genes implicated in innate immune responses, including several cytokines. Notably, AHR depletion reduced expression of IL23A and IL12B transcripts, which encode subunits of interleukin 23 (IL23), a macrophage cytokine that stimulates production of IL22 by innate lymphoid cells. The AHR directly induced IL23A transcription in human and mouse macrophages through near-upstream enhancer regions. Taken together, these findings show that AHR signaling is strongly engaged in Mtb-infected macrophages, and has widespread effects on innate immune responses. Moreover, they reveal a cascade of AHR-driven innate immune signaling, as IL1B (IL-1) and IL23 stimulate T cell subsets producing IL22, another direct target of AHR transactivation.
Engagement of the Aryl Hydrocarbon Receptor in Mycobacterium tuberculosis-Infected Macrophages Has Pleiotropic Effects on Innate Immune Signaling.
Cell line
View Samples