The goal of our study was to molecularly dissect mesothelioma tumor pathways by mean of microarray technologies in order to identify new tumor biomarkers, that could be used as early diagnostic markers and possibly as specific molecular therapeutic targets. We performed Affymetrix U133A plus 2.0 microarray analysis comparing 9 human pleural mesotheliomas with 4 normal pleural specimen. Stringent statistical feature selection detected a set of differentially expressed genes that were further evaluated to identify potential biomarkers to be used in early diagnostics. Selected genes were confirmed by RT-PCR. As reported by other mesothelioma profiling studies, most of genes are involved in G2/M transition. Our list contains several genes previously described as prognostic classifier. Furthermore, we found novel genes never associated before to mesothelioma and could be involved in tumor progression. Notable, the identification of MMP-14, a member of matrix metalloproteinase family. This molecule has been described as a new disease marker and could be used as biomarker also for mesothelioma early diagnosis and prognosis and that can be viewed as new and effective therapeutic target to test.
Global gene expression profiling of human pleural mesotheliomas: identification of matrix metalloproteinase 14 (MMP-14) as potential tumour target.
No sample metadata fields
View SamplesTranscript profile of 10 days-old seedlings over expressing miR396
Control of cell proliferation in Arabidopsis thaliana by microRNA miR396.
No sample metadata fields
View SamplesThe Growth Regulating Factors (GRFs) are plant specific transcription factors. They form complexes with GRF Interacting Factors (GIFs), a small family of transcriptional co-activators. In Arabidopsis thaliana, seven out of the nine GRFs are regulated by microRNA miR396. A detailed analysis of GRF3 revealed that a modified transgene, insensitive to the regulation of miR396, causes a strong increase in the number of cells in leaves, while an additional increase of GIF1 expression further enhances the number of cells synergistically. Genome-wide transcript profiling revealed that simultaneous increase of GRF3 and GIF1 levels causes additional effects in gene expression compared to either of the transgenes alone. We observed that GIF1 interacts in vivo with GRF3, as well as chromatin remodeling complexes, providing a mechanistic explanation for the additional activities of a GRF3-GIF1 complex. Interestingly, we found that the GRF system also regulates leaf longevity. Genetic and molecular analysis revealed that the functions of GRFs in leaf size and senescence can be uncoupled, demonstrating that the GRFs control different stages of leaf development. The results provide new insights into the functions of a complex regulatory network composed of microRNAs, transcription factors, and co-transcription factors.
Post-transcriptional control of GRF transcription factors by microRNA miR396 and GIF co-activator affects leaf size and longevity.
Specimen part
View SamplesAnalysis of gene expression in the meristematic zone of Arabidopsis roots overexpressing miR396
MicroRNA miR396 Regulates the Switch between Stem Cells and Transit-Amplifying Cells in Arabidopsis Roots.
Age, Specimen part
View SamplesWe used microarrays to assess gene expression changes in cells with siRNA-mediated knockdown of OPG compared to normal cells. Furthermore, we used microarrays to assess gene expression in cells treated with either RANKL or TRAIL compared to vehicle-treated cells.
No influence of OPG and its ligands, RANKL and TRAIL, on proliferation and regulation of the calcification process in primary human vascular smooth muscle cells.
Specimen part, Treatment
View SamplesIn Drosophila, PIWI proteins and bound PIWI interacting RNAs (piRNAs) form the core of a small RNA mediated defense system against selfish genetic elements. Within germline cells piRNAs are processed from piRNA clusters and transposons to be loaded into Piwi/Aubergine/AGO3 and a subset of piRNAs undergoes target dependent amplification. In contrast, gonadal somatic support cells express only Piwi, lack signs of piRNA amplification and exhibit primary piRNA biogenesis from piRNA clusters. Neither piRNA processing/loading nor Piwi mediated target silencing is understood at the genetic, cellular or molecular level. We developed an in vivo RNAi assay for the somatic piRNA pathway and identified the RNA helicase Armitage, the Tudor domain containing RNA helicase Yb and the putative nuclease Zucchini as essential factors for primary piRNA biogenesis. Lack of any of these proteins leads to transposon de-silencing, to a collapse in piRNA levels and to a failure in Piwi nuclear accumulation. We show that Armitage and Yb interact physically and co-localize in cytoplasmic Yb-bodies, which flank P-bodies. Loss of Zucchini leads to an accumulation of Piwi and Armitage in Yb-bodies indicating that Yb-bodies are sites of primary piRNA biogenesis. Overall design: small RNA libraries were prepared from Piwi immuno-precipitates of five different genotypes
An in vivo RNAi assay identifies major genetic and cellular requirements for primary piRNA biogenesis in Drosophila.
Subject
View SamplesThe aim of the study was to illucidate how BAFF mediates B cell survival and growth through the identification of BAFF-regulated genes.
BAFF controls B cell metabolic fitness through a PKC beta- and Akt-dependent mechanism.
No sample metadata fields
View SamplesAirway epithelium is the initial point of host-pathogen interaction in Pseudomonas aeruginosa infection, an important pathogen in cystic fibrosis and nosocomial pneumonia. We used global gene expression analysis to determine airway epithelial transcriptional responses dependent on matrilysin (MMP-7) and stromelysin-2 (MMP-10), two matrix metalloproteinases induced by acute P. aeruginosa pulmonary infection. Extraction of Differential Gene Expression (EDGE) analysis of gene expression changes in P. aeruginosa infected organotypic tracheal epithelial cell cultures from wildtype, Mmp7-/-, and Mmp10-/- mice identified 2,089 matrilysin-dependent and 1,628 stromelysin-2-dependent genes that were differentially expressed. Key node network analysis showed that these MMPs controlled distinct gene expression programs involved in proliferation, cell death, immune responses, and signal transduction, among other host defense processes. Our results demonstrate discrete roles for these MMPs in regulating epithelial responses to pseudomonas infection and show that a global genomics strategy can be used to assess MMP function.
Individual matrix metalloproteinases control distinct transcriptional responses in airway epithelial cells infected with Pseudomonas aeruginosa.
No sample metadata fields
View SamplesThis study examines the innate immune response of human pluripotent stem cell derived airway epithelium. Immune challenge was performed with TNF-alpha or bacterial lipopolysaccharide (LPS)
Innate immune response of human pluripotent stem cell-derived airway epithelium.
Specimen part, Treatment
View SamplesCraniosynostosis is a disease defined by premature fusion of one or more cranial sutures. The mechanistic pathology of isolated single-suture craniosynostosis is complex and while a number of genetic biomarkers and environmental predispositions have been identified, in many cases the causes remain controversial and inconclusive at best. After controlling for variables contributing to potential bias, FGF7, SFRP4, and VCAM1 emerged as potential genetic biomarkers for single-suture craniosynostosis due to their significantly large changes in gene expression compared to the control population. Furthermore, pathway analysis implicated focal adhesion and extracellular matrix (ECM)-receptor interaction as differentially regulated gene networks when comparing all cases of single-suture synostosis and controls. Lastly, overall gene expression was found to be highly conserved between coronal and metopic cases, as evidenced by the fact that WNT2 and IGFBP2 were the only differentially regulated genes identified in a direct comparison. These results not only confirm the roles of previously reported craniosynostosis-related targets but also introduce novel genetic biomarkers and pathways that may play critical roles in its pathogenesis.
Differential expression of extracellular matrix-mediated pathways in single-suture craniosynostosis.
Sex, Specimen part
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