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https://www.readbyqxmd.com/read/28079285/a-pathway-based-association-study-reveals-variants-from-wnt-signaling-genes-contributing-to-asthma-susceptibility
#1
A Barreto-Luis, A Corrales, M Acosta-Herrera, C Gonzalez-Colino, J Cumplido, J Martinez-Tadeo, A Carracedo, J Villar, T Carrillo, M Pino-Yanes, C Flores
BACKGROUND: Genetic susceptibility to asthma is currently linked to a handful of genes which have a limited ability to predict the overall disease risk, suggesting the existence of many other genes involved in disease development. Accumulated evidence from association studies in genes related by biological pathways could reveal novel asthma genes. OBJECTIVE: To reveal novel asthma susceptibility genes by means of a pathway-based association study. METHODS: Based on summary data from a previous a genome-wide association study (GWAS) of asthma, we first identified significant biological pathways using a gene-set enrichment analysis...
January 12, 2017: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28077379/effects-of-supplementation-with-nondigestible-carbohydrates-on-fecal-calprotectin-and-on-epigenetic-regulation-of-sfrp1-expression-in-the-large-bowel-mucosa-of-healthy-individuals
#2
Fiona C Malcomson, Naomi D Willis, Iain McCallum, Long Xie, Idoia Ibero-Baraibar, Wing C Leung, Seamus Kelly, D Michael Bradburn, Nigel J Belshaw, Ian T Johnson, John C Mathers
BACKGROUND: Hyperactive Wnt signaling is frequently observed in colorectal cancer. Higher intakes of dietary fiber [nondigestible carbohydrates (NDCs)] and the fermentation product butyrate are protective against colorectal cancer and may exert their preventative effects via modulation of the Wnt pathway. OBJECTIVES: We investigated the effects of supplementing healthy individuals with 2 NDCs [resistant starch (RS) and polydextrose] on fecal calprotectin concentrations and Wnt pathway-related gene expression...
January 11, 2017: American Journal of Clinical Nutrition
https://www.readbyqxmd.com/read/28069793/decreased-wnt-%C3%AE-catenin-signalling-contributes-to-the-pathogenesis-of-dilated-cardiomyopathy-caused-by-mutations-in-the-lamin-a-c-gene
#3
Caroline Le Dour, Coline Macquart, Fusako Sera, Shunichi Homma, Gisele Bonne, John P Morrow, Howard J Worman, Antoine Muchir
Cardiomyopathy caused by lamin A/C gene (LMNA) mutations (hereafter referred as LMNA cardiomyopathy) is characterized by cardiac conduction abnormalities and left ventricular systolic dysfunction predisposing to heart failure. Previous cardiac transcriptional profiling of Lmna(H222P/H222P) mouse, a small animal model of LMNA cardiomyopathy, suggested decreased WNT/β-catenin signalling. We confirmed decreased WNT/β-catenin signalling in the hearts of these mice by demonstrating decreased β-catenin and WNT proteins...
January 9, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28063934/morphine-administration-induces-change-in-anxiety-related-behavior-via-wnt-%C3%AE-catenin-signaling
#4
Jiancai Wang, Gang Zhu, Lu Huang, Tiejian Nie, Kai Tao, Yuqian Li, Guodong Gao
Chronic morphine administration is known to decrease anxiety-related behavior, which may lead to morphine-seeking and other social problems. Recent studies have revealed that Wnt/β-catenin signaling plays an important role in anxiety-related behavior. We used HT22 cells, which were derived from primary mouse hippocampal neuronal cultures, to explore the relationship between Wnt signaling and morphine exposure. Many techniques, such as western blot analysis, immunofluorescence and luciferase assays, were utilized...
January 4, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28062160/loss-of-secreted-frizzled-related-protein-1-expression-is-associated-with-poor-prognosis-in-intrahepatic-cholangiocarcinoma
#5
M Davaadorj, Y Saito, Y Morine, T Ikemoto, S Imura, C Takasu, S Yamada, T Hiroki, M Yoshikawa, M Shimada
AIMS: Secreted Frizzled-Related Protein-1 (SFRP1) is a well-known negative regulator of the wingless type (Wnt)-β-catenin pathway and its inactivation plays an important role in the development and progression of many cancers. In this study, we aimed to determine the clinical significance of SFRP1 expression in intrahepatic cholangiocarcinoma (IHCC) and to define the relationship to Wnt-β-catenin pathway. METHODS: Fifty IHCC patients who had liver resection were enrolled in this study...
December 24, 2016: European Journal of Surgical Oncology
https://www.readbyqxmd.com/read/28058013/aging-related-methylation-influences-the-gene-expression-of-key-control-genes-in-colorectal-cancer-and-adenoma
#6
Orsolya Galamb, Alexandra Kalmár, Barbara Kinga Barták, Árpád V Patai, Katalin Leiszter, Bálint Péterfia, Barnabás Wichmann, Gábor Valcz, Gábor Veres, Zsolt Tulassay, Béla Molnár
AIM: To analyze colorectal carcinogenesis and age-related DNA methylation alterations of gene sequences associated with epigenetic clock CpG sites. METHODS: In silico DNA methylation analysis of 353 epigenetic clock CpG sites published by Steve Horvath was performed using methylation array data for a set of 123 colonic tissue samples [64 colorectal cancer (CRC), 42 adenoma, 17 normal; GEO accession number: GSE48684]. Among the differentially methylated age-related genes, secreted frizzled related protein 1 (SFRP1) promoter methylation was further investigated in colonic tissue from 8 healthy adults, 19 normal children, 20 adenoma and 8 CRC patients using bisulfite-specific PCR followed by methylation-specific high resolution melting (MS-HRM) analysis...
December 21, 2016: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28002843/loss-of-zebrafish-mfrp-causes-nanophthalmia-hyperopia-and-accumulation-of-subretinal-macrophages
#7
Ross F Collery, Peter J Volberding, Jonathan R Bostrom, Brian A Link, Joseph C Besharse
Purpose: Mutations in membrane frizzled-related protein (MFRP) are associated with nanophthalmia, hyperopia, foveoschisis, irregular patches of RPE atrophy, and optic disc drusen in humans. Mouse mfrp mutants show retinal degeneration but no change in eye size or refractive state. The goal of this work was to generate zebrafish mutants to investigate the loss of Mfrp on eye size and refractive state, and to characterize other phenotypes observed. Methods: Clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 methods were used to generate multiple frameshift mutations in zebrafish mfrp causing premature translational stops in Mfrp...
December 1, 2016: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/27996212/ectodermal-neural-cortex-1-isoforms-have-contrasting-effects-on-mc3t3-e1-osteoblast-mineralization-and-gene-expression
#8
Leah E Worton, Yan-Chuan Shi, Elisabeth J Smith, Simon C Barry, Thomas J Gonda, Jonathan P Whitehead, Edith M Gardiner
The importance of Wnt pathway signaling in development of bone has been well established. Here we investigated the role of a known Wnt target, ENC1 (ectodermal-neural cortex 1; NRP/B), in osteoblast differentiation. Enc1 expression was detected in mouse osteoblasts, chondrocytes and osteocytes by in situ hybridization, and osteoblastic expression was verified in differentiating primary cultures and MC3T3-E1 pre-osteoblast cells, with 57kDa and 67kDa ENC1 protein isoforms detected throughout differentiation...
December 20, 2016: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/27986984/bone-marrow-sfrp5-level-is-negatively-associated-with-bone-formation-markers
#9
H Chen, Y He, D Wu, G Dai, C Zhao, W Huang, D Jiang
: Secreted frizzled-related protein 5 (sFRP5) level in bone marrow environment is inversely correlated with bone formation markers, suggesting that it decreases bone mass by inhibiting bone formation. Besides, it functions in a local fashion when regulating bone metabolism. sFRP5 may be a target when developing anti-osteoporotic agents. INTRODUCTION: The purpose of the study is to investigate the relationship between bone marrow sFRP5 level and bone turnover state...
December 17, 2016: Osteoporosis International
https://www.readbyqxmd.com/read/27959380/sequencing-and-bioinformatics-analysis-of-the-differentially-expressed-genes-in-herniated-discs-with-or-without-calcification
#10
Jia Shao, Miao Yu, Liang Jiang, Fengliang Wu, Xiaoguang Liu
The purpose of this study was to detect the differentially expressed genes between ossified herniated discs and herniated discs without ossification. In addition, we sought to identify a few candidate genes and pathways by using bioinformatics analysis. We analyzed 6 samples each of ossified herniated discs (experimental group) and herniated discs without ossification (control group). Purified mRNA and cDNA extracted from the samples were subjected to sequencing. The NOISeq method was used to statistically identify the differentially expressed genes (DEGs) between the 2 groups...
January 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/27930333/tet-proteins-influence-the-balance-between-neuroectodermal-and-mesodermal-fate-choice-by-inhibiting-wnt-signaling
#11
Xiang Li, Xiaojing Yue, William A Pastor, Lizhu Lin, Romain Georges, Lukas Chavez, Sylvia M Evans, Anjana Rao
TET-family dioxygenases catalyze conversion of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) and oxidized methylcytosines in DNA. Here, we show that mouse embryonic stem cells (mESCs), either lacking Tet3 alone or with triple deficiency of Tet1/2/3, displayed impaired adoption of neural cell fate and concomitantly skewed toward cardiac mesodermal fate. Conversely, ectopic expression of Tet3 enhanced neural differentiation and limited cardiac mesoderm specification. Genome-wide analyses showed that Tet3 mediates cell-fate decisions by inhibiting Wnt signaling, partly through promoter demethylation and transcriptional activation of the Wnt inhibitor secreted frizzled-related protein 4 (Sfrp4)...
December 20, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27926869/robust-asymmetric-localization-of-planar-polarity-proteins-is-associated-with-organization-into-signalosome-like-domains-of-variable-stoichiometry
#12
Helen Strutt, Jessica Gamage, David Strutt
In developing epithelia, the core planar polarity proteins physically interact with each other and localize asymmetrically at opposite cell ends, forming intercellular complexes that link the polarity of neighboring cells. Using quantitative imaging to examine the composition of the core protein complex in vivo, we find that complex composition is unexpectedly plastic. The transmembrane proteins Frizzled and Flamingo form a stoichiometric nucleus in the complex, while the relative levels of the other four core proteins can vary independently...
December 6, 2016: Cell Reports
https://www.readbyqxmd.com/read/27920883/exogenous-secreted-frizzled-related-protein-4-modulates-steroidogenesis-of-rat-granulosa-cells-through-wnt-%C3%AE-catenin-and-pi3k-akt-signaling-pathways
#13
Ghamartaj Hossein, Manijeh Khanmohammadi, Parisa Sahranavard Fard, Yasaman Heidarian, Somaieh Kazemnejad, Mohammad Mehdi Akhondi
BACKGROUND: It has been reported that secreted frizzled-related protein-4 known as an antagonist of Wnt signaling pathway plays a role in luteinization process of rodent granulosa cells. The purpose of this study was twofold: 1) to determine whether recombinant human secreted frizzled-related protein-4 (rhSFRP-4) could directly induce terminal differentiation of rat Granulosa Cells (GCs) and 2) to understand how the modulation of β-catenin and Protein Kinase B (PKB)/AKT activity by exogenous SFRP-4 could be involved in steroidogenesis...
October 2016: Avicenna Journal of Medical Biotechnology
https://www.readbyqxmd.com/read/27904780/low-expression-of-rbms3-and-sfrp1-are-associated-with-poor-prognosis-in-patients-with-gastric-cancer
#14
Tao Zhang, Youliang Wu, Zheng Fang, Qiang Yan, Shangxin Zhang, Ruochuan Sun, Junaid Khaliq, Yongxiang Li
RNA binding motif, single stranded interacting protein 3 (RBMS3) has been reported as a tumor suppressor gene (TSG) in some squamous carcinoma. However, its expression levels and clinical significance in gastric cancer (GC) remains unclear. Secreted frizzled-related protein 1 (SFRP1) plays a role of tumor suppressor in many cancers by inhibiting Wnt/β-catenin pathway. Nevertheless, its expression levels and clinical significance in GC are in dispute. In this study, quantitative real-time PCR and Western Blot were used to measure the mRNA and protein level of RBMS3 and SFRP1 in 23 fresh GC and corresponding normal tissues...
2016: American Journal of Cancer Research
https://www.readbyqxmd.com/read/27890011/microrna-mir-130b-promotes-wear-particle-induced-osteolysis-via-down-regulating-frizzled-related-protein-frzb
#15
De-Zhi Zheng, Lei Wang, Yan-Min Bu, Jun Liu
Periprosthetic osteolysis induced by wear particles can lead to aseptic loosening, one main reason of arthroplasty failure. However, the role of microRNA-130b (miR-130b) in particle-induced osteolysis (PIO) has not been explored yet. In this study, PIO models were established in C57BL/J6 mice via the implantation of Co-Cr-Mo alloy particles, and evaluated by detecting tartrate-resistant acid phosphatase (TRAP) activity and bone resorption in the calvaria. Mouse preosteoblast MC3T3-E1 cells were cultured to receive particle stimulation in vitro...
November 23, 2016: Current Neurovascular Research
https://www.readbyqxmd.com/read/27883247/2-methoxyestradiol-mediated-induction-of-frzb-contributes-to-cell-death-and-autophagy-in-mg63-osteosarcoma-cells
#16
Dalibel Bravo, Kristen L Shogren, Dongqing Zuo, Eric R Wagner, Gobinda Sarkar, Michael J Yaszemski, Avudaiappan Maran
Osteosarcoma is a bone tumor that mainly affects children and adolescents. Although its pathogenesis is still not fully understood, activation of Wnt signaling has been implicated in the development and metastasis of osteosarcoma. In this report, we have investigated the effect of the anti-tumor compound, 2-methoxyestradiol (2-ME) on Wnt antagonist frizzled-related protein b (Frzb), also known as secreted frizzled-related protein (sFRP)3 in human osteosarcoma (MG63) cells. Our results show that 2-ME treatment induces Frzb gene promoter activity, and increases Frzb mRNA and protein levels in osteosarcoma cells...
November 24, 2016: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/27878554/the-involvement-of-the-decrease-of-astrocytic-wnt5a-in-the-cognitive-decline-in-minimal-hepatic-encephalopathy
#17
Saidan Ding, Zhu Xu, Jianjing Yang, Leping Liu, Xueli Huang, Xuebao Wang, Qichuan Zhuge
Wnt signaling plays a key role in neuroprotection and synaptic plasticity. We speculate that the impairment of Wnt signaling may mediate astrocytic neurotrophins (NTs) production and the impairment of Wnt signaling to astrocytic NTs production contributes to the pathogenesis of minimal hepatic encephalopathy (MHE). Here, we found that induction of astrocytic NTs synthesis was by Wnt5a via the calcium/calmodulin-sensitive protein kinase II (CaMK II)-cAMP-response element-binding protein (CREB) pathway in PCAs...
November 22, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27869803/genome-wide-crispr-screens-reveal-a-wnt-fzd5-signaling-circuit-as-a-druggable-vulnerability-of-rnf43-mutant-pancreatic-tumors
#18
Zachary Steinhart, Zvezdan Pavlovic, Megha Chandrashekhar, Traver Hart, Xiaowei Wang, Xiaoyu Zhang, Mélanie Robitaille, Kevin R Brown, Sridevi Jaksani, René Overmeer, Sylvia F Boj, Jarrett Adams, James Pan, Hans Clevers, Sachdev Sidhu, Jason Moffat, Stéphane Angers
Forward genetic screens with CRISPR-Cas9 genome editing enable high-resolution detection of genetic vulnerabilities in cancer cells. We conducted genome-wide CRISPR-Cas9 screens in RNF43-mutant pancreatic ductal adenocarcinoma (PDAC) cells, which rely on Wnt signaling for proliferation. Through these screens, we discovered a unique requirement for a Wnt signaling circuit: engaging FZD5, one of the ten Frizzled receptors encoded in the human genome. Our results uncover an underappreciated level of context-dependent specificity at the Wnt receptor level...
January 2017: Nature Medicine
https://www.readbyqxmd.com/read/27859262/functional-and-prognostic-significance-of-the-genomic-amplification-of-frizzled-6-fzd6-in-breast-cancer
#19
Gabriele Corda, Gianluca Sala, Rossano Lattanzio, Manuela Iezzi, Michele Sallese, Giorgia Fragassi, Alessia Lamolinara, Hasan Mirza, Daniela Barcaroli, Sibylle Ermler, Elisabete Silva, Hemad Yasaei, Robert F Newbold, Paola Vagnarelli, Marcella Mottolese, Pier Giorgio Natali, Letizia Perracchio, Jelmar Quist, Anita Grigoriadis, Pierfrancesco Marra, Andrew N Tutt, Mauro Piantelli, Stefano Iacobelli, Vincenzo De Laurenzi, Arturo Sala
Frizzled receptors mediate Wnt ligand signalling, which is crucially involved in regulating tissue development and differentiation, and is often deregulated in cancer. In this study, we found that the gene encoding the Wnt receptor frizzled 6 (FZD6) is frequently amplified in breast cancer, with an increased incidence in the triple-negative breast cancer (TNBC) subtype. Ablation of FZD6 expression in mammary cancer cell lines: (1) inhibited motility and invasion; (2) induced a more symmetrical shape of organoid three-dimensional cultures; and (3) inhibited bone and liver metastasis in vivo...
November 9, 2016: Journal of Pathology
https://www.readbyqxmd.com/read/27852064/overexpression-of-fzd7-promotes-glioma-cell-proliferation-by-upregulating-taz
#20
Xia Qiu, Jianguo Jiao, Yidong Li, Tian Tian
Gliomas are the most prevalent type of primary brain tumors in adults, accounting for more than 40% of neoplasm in the central nervous system. Frizzled-7 (FZD7) is a seven-pass trans-membrane Wnt receptor that plays a critical role in the development of various tumors. In this study, we detected high-level FZD7 expression in glioma and its overexpression was associated with advanced tumor stage. In vitro functional assays showed that forced overexpression of FZD7 promoted proliferation of gliomas cells, whereas knockdown of endogenous FZD7 significantly suppressed proliferation ability of these cells...
November 11, 2016: Oncotarget
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