Search results for "Signaling pathway."
showing 10 items of 281 documents
P–543 Inhibition of cell proliferation and extracellular matrix formation in human uterine leiomyomas by 5-aza–2’-deoxycitidine via Wnt/ β-catenin pa…
2021
Abstract Study question Is DNA methylation reversion through DNA methyltransferases (DNMT) inhibitors, such as 5-aza–2’-deoxycitidine, a potential therapeutic option for treatment of patients with uterine leiomyomas (UL)? Summary answer 5-aza–2’-deoxycitidine reduces proliferation and extracellular matrix (ECM) formation by inhibition of Wnt/ β-catenin pathway on UL cells, suggesting DNMT inhibitors as an option to treat UL. What is known already: UL is a multifactorial disease with an unclear pathogenesis and inaccurate treatment. Aberrant DNA methylation have been found in UL compared to myometrium (MM) tissue, showing hypermethylation of tumor suppressor genes, which contributes to the d…
MicroRNAs Associated With Biological Pathways of Left- and Right-sided Colorectal Cancer.
2020
BACKGROUND/AIM MicroRNAs (miRNAs) regulate the development of colorectal cancer (CRC). We aimed to investigate miRNAs and their relation to cancer-related signaling pathways in site-specific CRC. MATERIALS AND METHODS We used a total of 24 left- and right-sided Finnish CRC samples (discovery cohort) and The Cancer Genome Atlas public mature miRSeq dataset of 201 CRC samples (validation cohort). MiRNA differential expression and biological pathway analyses were performed using DESeq2 and the DIANA/mirPath tool, respectively. RESULTS We found 17 significantly differentially up-regulated [false discovery rate (FDR) <0.05] miRNAs in left-sided CRC ("left miRNAs"), and 15 in right-sided CRC ("ri…
Polarity factor 'Frizzled' in the demosponge Suberites domuncula: identification, expression and localization of the receptor in the epithelium/pinac…
2003
Until recently, it was assumed that polarity and axis formation have evolved only in metazoan phyla higher than Cnidaria. One key molecule involved in the signal transduction causing tissue polarity is Frizzled, a seven-transmembrane receptor that is activated by the Wnt family of secreted proteins. We report the isolation and characterization of a Frizzled gene from the demosponge Suberites domuncula (Sd-Fz). The deduced polypeptide comprises all characteristic domains known from Frizzled receptors of higher metazoans. In situ hybridization studies show that Sd-Fz is expressed in cells close to the surface of the sponges and in the pinacocytes of some canals. Northern blot analysis demonst…
Isolation and characterization of Wnt pathway-related genes from Porifera.
2006
The Wnt signal acts by binding to Frizzled receptors, with the subsequent activation of two different signal transduction cascades, the canonical and the non-canonical Wnt pathways, involved in cell growth, differentiation, migration and fate. The canonical pathway functions through the translocation of beta-catenin to the nucleus and the activation of TCF/LEF transcription factors; it plays an important role in developmental patterning and cell fate decisions during embryogenesis. The non-canonical Wnt pathway is responsible for the planar cell polarity process in invertebrates, and for the convergent-extension movements during vertebrate gastrulation. The final effect of the non-canonical…
Regional and modular expression of morphogenetic factors in the demosponge Lubomirskia baicalensis
2008
Some sponges [phylum Porifera], e.g. the demosponges Lubomirskia baicalensis or Axinella polypoides, show an arborescent growth form. In the freshwater sponge L. baicalensis this morphotype is seen mostly in depths below 4 m while in more shallow regions it grows as a crust. The different growth forms are determined in nature very likely by water current and/or light. The branches of this species are composed of modules, arranged along the apical-basal axis. The modules are delimited by a precise architecture of the spicule bundles; longitudinal bundles originate from the apex of the earlier module, while at the basis of each module these bundles are cross-linked by traverse bundles under f…
Oxidative stress inhibits IFN-α-induced antiviral gene expression by blocking the JAK–STAT pathway
2006
Abstract BACKGROUND/AIMS: Unresponsiveness to IFN-alpha is common in chronic hepatitis C. Since conditions associated with an increased oxidative stress (advanced age, steatosis, fibrosis, iron overload, and alcohol consumption) reduce the likelihood of response, we hypothesized that oxidative stress may affect the antiviral actions of IFN-alpha. METHODS: We examined in a human hepatocellular carcinoma cell line (Huh-7) the effect of hydrogen peroxide (H2O2), as a generator of oxidative stress, on the IFN-alpha signaling pathway. RESULTS: Pretreatment of Huh-7 cells with 0.5-1 mM H2O2 resulted in the suppression of the IFN-alpha-induced antiviral protein MxA and of IRF-9 mRNA expression. Th…
RSPO2 gene rearrangement: a powerful driver of β-catenin activation in liver tumours
2019
ObjectiveWe aimed at the identification of genetic alterations that may functionally substitute for CTNNB1 mutation in ß-catenin-activated hepatocellular adenomas (HCAs) and hepatocellular carcinoma (HCC).DesignLarge cohorts of HCA (n=185) and HCC (n=468) were classified using immunohistochemistry. The mutational status of the CTNNB1 gene was determined in ß-catenin-activated HCA (b-HCA) and HCC with at least moderate nuclear CTNNB1 accumulation. Ultra-deep sequencing was used to characterise CTNNB1wild-type and ß-catenin-activated HCA and HCC. Expression profiling of HCA subtypes was performed.ResultsA roof plate-specific spondin 2 (RSPO2) gene rearrangement resulting from a 46.4 kb microd…
Targeting the JAK/STAT Pathway: A Combined Ligand- and Target-Based Approach
2021
Janus kinases (JAKs) are a family of proinflammatory enzymes able to mediate the immune responses and the inflammatory cascade by modulating multiple cytokine expressions as well as various growth factors. In the present study, the inhibition of the JAK-signal transducer and activator of transcription (STAT) signaling pathway is explored as a potential strategy for treating autoimmune and inflammatory disorders. A computationally driven approach aimed at identifying novel JAK inhibitors based on molecular topology, docking, and molecular dynamics simulations was carried out. For the best candidates selected, the inhibitory activity against JAK2 was evaluated in vitro. Two hit compounds with…
Lrp4, a Novel Receptor for Dickkopf 1 and Sclerostin, Is Expressed by Osteoblasts and Regulates Bone Growth and Turnover In Vivo
2009
Lrp4 is a multifunctional member of the low density lipoprotein-receptor gene family and a modulator of extracellular cell signaling pathways in development. For example, Lrp4 binds Wise, a secreted Wnt modulator and BMP antagonist. Lrp4 shares structural elements within the extracellular ligand binding domain with Lrp5 and Lrp6, two established Wnt co-receptors with important roles in osteogenesis. Sclerostin is a potent osteocyte secreted inhibitor of bone formation that directly binds Lrp5 and Lrp6 and modulates both BMP and Wnt signaling. The anti-osteogenic effect of sclerostin is thought to be mediated mainly by inhibition of Wnt signaling through Lrp5/6 within osteoblasts. Dickkopf1 …
Association of JAK-STAT pathway related genes with lymphoma risk: results of a European case-control study (EpiLymph)
2011
Previous studies have suggested an important role for the Janus kinase-signal transducer and activator of transcription (JAK-STAT) signalling pathway in tumour development. Therefore, we explored genetic variants in JAK-STAT pathway associated genes with lymphoma risk. In samples of the EpiLymph case-control study we genotyped 1536 single nucleotide polymorphisms (SNPs) using GoldenGate BeadArray™ Technology (Illumina, San Diego, CA, USA). Here, we report the associations between selected SNPs and haplotypes of the JAK-STAT pathway and risk of Hodgkin lymphoma (HL), B-cell non-Hodgkin lymphoma (B-NHL) and most frequent B-NHL subtypes. Among 210 relevant JAK-STAT pathway-related SNPs, polymo…