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https://www.readbyqxmd.com/read/28288968/depletion-of-tcf3-and-lef1-maintains-mouse-embryonic-stem-cell-self-renewal
#1
Shoudong Ye, Tao Zhang, Chang Tong, Xingliang Zhou, Kan He, Qian Ban, Dahai Liu, Qi-Long Ying
Mouse and rat embryonic stem cell (ESC) self-renewal can be maintained by dual inhibition of glycogen synthase kinase 3 (GSK3) and mitogen-activated protein kinase kinase (MEK). Inhibition of GSK3 promotes ESC self-renewal by abrogating T-cell factor 3 (TCF3)-mediated repression of the pluripotency network. How inhibition of MEK mediates ESC self-renewal, however, remains largely unknown. Here, we show that inhibition of MEK can significantly suppress lymphoid enhancer factor 1 (LEF1) expression in mouse ESCs...
March 13, 2017: Biology Open
https://www.readbyqxmd.com/read/28288164/bayesian-model-of-signal-rewiring-reveals-mechanisms-of-gene-dysregulation-in-acquired-drug-resistance-in-breast-cancer
#2
A K M Azad, Alfons Lawen, Jonathan M Keith
Small molecule inhibitors, such as lapatinib, are effective against breast cancer in clinical trials, but tumor cells ultimately acquire resistance to the drug. Maintaining sensitization to drug action is essential for durable growth inhibition. Recently, adaptive reprogramming of signaling circuitry has been identified as a major cause of acquired resistance. We developed a computational framework using a Bayesian statistical approach to model signal rewiring in acquired resistance. We used the p1-model to infer potential aberrant gene-pairs with differential posterior probabilities of appearing in resistant-vs-parental networks...
2017: PloS One
https://www.readbyqxmd.com/read/28287244/functional-differences-between-tcf1-isoforms-in-early-xenopus-development
#3
Giulietta Roël, Olaf Van Den Broek, Olivier Destrée
In Xenopus gastrula stage embryos, four isoforms of Tcf1 (B, C, D and E) are present with high amino acid sequence conservation compared to fish, mice and human. We studied possible functional differences between these Tcf1 isoforms during early Xenopus development. After overexpression of single Tcf1 isoforms, two distinct phenotypes were observed. Overexpression of the B or D isoforms of Tcf1, which both lack a C-clamp, enhances early canonical Wnt signaling and induces ectopic dorsal mesoderm at the expense of ventrolateral mesoderm prior to gastrulation, causing severe antero-dorzalization of embryos...
2017: International Journal of Developmental Biology
https://www.readbyqxmd.com/read/28278156/a-new-mode-of-dna-binding-distinguishes-capicua-from-other-hmg-box-factors-and-explains-its-mutation-patterns-in-cancer
#4
Marta Forés, Lucía Simón-Carrasco, Leiore Ajuria, Núria Samper, Sergio González-Crespo, Matthias Drosten, Mariano Barbacid, Gerardo Jiménez
HMG-box proteins, including Sox/SRY (Sox) and TCF/LEF1 (TCF) family members, bind DNA via their HMG-box. This binding, however, is relatively weak and both Sox and TCF factors employ distinct mechanisms for enhancing their affinity and specificity for DNA. Here we report that Capicua (CIC), an HMG-box transcriptional repressor involved in Ras/MAPK signaling and cancer progression, employs an additional distinct mode of DNA binding that enables selective recognition of its targets. We find that, contrary to previous assumptions, the HMG-box of CIC does not bind DNA alone but instead requires a distant motif (referred to as C1) present at the C-terminus of all CIC proteins...
March 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28273108/structure-based-mutational-analysis-of-icat-residues-mediating-negative-regulation-of-%C3%AE-catenin-co-transcriptional-activity
#5
Mélanie J Domingues, Juan Martinez-Sanz, Laura Papon, Lionel Larue, Liliane Mouawad, Jacky Bonaventure
ICAT (Inhibitor of β-CAtenin and TCF) is a small acidic protein that negatively regulates β-catenin co-transcriptional activity by competing with TCF/LEF factors in their binding to β-catenin superhelical core. In melanoma cells, ICAT competes with LEF1 to negatively regulate the M-MITF and NEDD9 target genes. The structure of ICAT consists of two domains: the 3-helix bundle N-terminal domain binds to β-catenin Armadillo (Arm) repeats 10-12 and the C-terminal tail binds to Arm repeats 5-9. To elucidate the structural mechanisms governing ICAT/β-catenin interactions in melanoma cells, three ICAT residues Y15, K19 and V22 in the N-terminal domain, contacting hydrophobic β-catenin residue F660, were mutated and interaction was assessed by immunoprecipitation...
2017: PloS One
https://www.readbyqxmd.com/read/28259909/prostate-apoptosis-response-4-par4-expression-modulates-wnt-signaling-pathways-in-mcf7-breast-cancer-cells-a-possible-mechanism-underlying-par4-mediated-docetaxel-chemosensitivity
#6
Simone Aparecida de Bessa Garcia, Ana Carolina Pavanelli, Natália Cruz E Melo, Maria Aparecida Nagai
Docetaxel is an effective drug for the treatment of metastatic breast cancer. However, the exact mechanisms and/or markers associated with chemosensitivity or resistance to docetaxel remain unclear. We previously showed that the expression of prostate apoptosis response 4 (PAR4) inhibits the growth of MCF7 breast cancer cells and increases their sensitivity to docetaxel. Using cDNA microarray analysis, we evaluated transcriptome changes in MCF7 cells expressing increased levels of PAR4 and control cells before and after docetaxel treatment...
February 21, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28252047/inhibition-of-proliferation-and-epithelial-mesenchymal-transition-in-retinal-pigment-epithelial-cells-by-heavy-chain-hyaluronan-pentraxin-3
#7
Hua He, Ajay E Kuriyan, Chen-Wei Su, Megha Mahabole, Yuan Zhang, Ying-Ting Zhu, Harry W Flynn, Jean-Marie Parel, Scheffer C G Tseng
Proliferative vitreoretinopathy (PVR) is mediated by proliferation and epithelial mesenchymal transition (EMT) of retinal pigment epithelium (RPE). Because heavy chain-hyaluronic acid/pentraxin 3 (HC-HA/PTX3) purified from human amniotic membrane exerts anti-inflammatory and anti-scarring actions, we hypothesized that HC-HA/PTX3 could inhibit these PVR-related processes in vitro. In this study, we first optimized an ARPE-19 cell culture model to mimic PVR by defining cell density, growth factors, and cultivation time...
March 2, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28231299/exploration-of-inhibitory-mechanisms-of-curcumin-in-lung-cancer-metastasis-using-a-mirna-transcription-factor-target-gene-network
#8
De-Min Jiao, Li Yan, Li-Shan Wang, Hui-Zhen Hu, Xia-Li Tang, Jun Chen, Jian Wang, You Li, Qing-Yong Chen
The present study was aimed to unravel the inhibitory mechanisms of curcumin for lung cancer metastasis via constructing a miRNA-transcription factor (TF)-target gene network. Differentially expressed miRNAs between human high-metastatic non-small cell lung cancer 95D cells treated with and without curcumin were identified using a TaqMan human miRNA array followed by real-time PCR, out of which, the top 6 miRNAs (miR-302b-3p, miR-335-5p, miR-338-3p, miR-34c-5p, miR-29c-3p and miR-34a-35p) with more verified target genes and TFs than other miRNAs as confirmed by a literature review were selected for further analysis...
2017: PloS One
https://www.readbyqxmd.com/read/28222387/baicalein-enhances-the-osteogenic-differentiation-of-human-periodontal-ligament-cells-by-activating-the-wnt-%C3%AE-catenin-signaling-pathway
#9
Li-Jiao Chen, Bi-Bo Hu, Xin-Lian Shi, Man-Man Ren, Wen-Bin Yu, Sheng-Dan Cen, Rong-Dang Hu, Hui Deng
OBJECTIVE: Periodontium regeneration is one of the most important processes for periodontitis therapy. Human periodontal ligament cells (hPDLCs) play a vital role in the repair and regeneration of periodontal tissues. Our study aimed to investigated the mechanisms underlying the promotion of hPLDCs osteogenic differentiation by baicalein. DESIGN: hPDLCs were obtained from periodontal ligament (PDL) tissues by primary culture. The MTT assay was used to determine the growth curves of hPDLCs treated with different concentrations of baicalein (1...
February 7, 2017: Archives of Oral Biology
https://www.readbyqxmd.com/read/28220305/homeobox-wnt-and-fibroblast-growth-factor-signaling-is-augmented-during-alveogenesis-in-mice-lacking-superoxide-dismutase-3-extracellular
#10
Tania A Thimraj, Rahel L Birru, Ankita Mitra, Holger Schulz, George D Leikauf, Koustav Ganguly
Superoxide dismutase 3, extracellular (SOD3) polymorphisms have been implicated in reduced pulmonary function development and altered risk for chronic obstructive pulmonary disease. We previously reported that gene-targeted Sod3-/- mice have impaired lung function and human SOD3 variants are associated with reduced pulmonary function in children. Reduced lung SOD3 levels were reported in mice with lower lung function with the greatest difference occurring during alveogenesis phase [postnatal (P) days 14-28]...
February 20, 2017: Lung
https://www.readbyqxmd.com/read/28185954/wip1-directly-dephosphorylates-nlk-and-increases-wnt-activity-during-germ-cell-development
#11
Seung-Ju Cho, Bok-Sik Cha, Ok-Seon Kwon, Jisun Lim, Dong-Myung Shin, Dong Wook Han, Tohru Ishitani, Eek-Hoon Jho, Albert J Fornace, Hyuk-Jin Cha
Mice null for wild-type p53-induced phosphatase 1 (WIP1) display defects in testis development and spermatogenesis, resulting in reduced fertility. However, the molecular mechanism underlying these abnormalities in the testis remains uncharacterized. We report that the phosphatase activity of WIP1 increases Wnt activity through Nemo-like kinase (NLK). WIP1 directly interacted with NLK, which is highly homologous to p38 MAPK, a WIP1 substrate, and dephosphorylated its activation site. The WIP1-mediated inhibition of NLK activity markedly decreased the phosphorylation of lymphoid enhancer-binding factor 1 (LEF1), enhancing its interaction with β-catenin...
April 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28122350/transcriptional-suppression-of-microrna-27a-contributes-to-laryngeal-cancer-differentiation-via-gsk-3%C3%AE-involved-wnt-%C3%AE-catenin-pathway
#12
Sheng Chen, Yuan-Yuan Sun, Zhao-Xiong Zhang, Yun-Hui Li, Zhen-Ming Xu, Wei-Neng Fu
miR-27a regulates cell differentiation in a variety of diseases. However, whether and how miR-27a participates in laryngeal cancer cell differentiation remains unknown. Therefore, we explored role and molecular mechanism of miR-27a in laryngeal cancer differentiation in the study. We found that miR-27a expression was inversely correlated with laryngeal cancer differentiation degree based on the clinical pathological diagnosis of each patient. miR-27 asignificantly rescued differentiation and inhibited β-catenin, LEF1, OCT4 and SOX2 in Wnt/β-catenin pathway in all-trans-retinoic acid (ATRA)-induced laryngeal cancer cells...
January 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/28118819/short-bowel-syndrome-results-in-increased-gene-expression-associated-with-proliferation-inflammation-bile-acid-synthesis-and-immune-system-activation-rna-sequencing-a-zebrafish-sbs-model
#13
Kathy A Schall, Matthew E Thornton, Mubina Isani, Kathleen A Holoyda, Xiaogang Hou, Ching-Ling Lien, Brendan H Grubbs, Tracy C Grikscheit
BACKGROUND: Much of the morbidity associated with short bowel syndrome (SBS) is attributed to effects of decreased enteral nutrition and administration of total parenteral nutrition (TPN). We hypothesized that acute SBS alone has significant effects on gene expression beyond epithelial proliferation, and tested this in a zebrafish SBS model. METHODS: In a model of SBS in zebrafish (laparotomy, proximal stoma, distal ligation, n = 29) or sham (laparotomy alone, n = 28) surgery, RNA-Seq was performed after 2 weeks...
January 25, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28103583/angiogenesis-related-genes-may-be-a-more-important-factor-than-matrix-metalloproteinases-in-bronchopulmonary-dysplasia-development
#14
Min Yang, Bo-Lin Chen, Jian-Bao Huang, Yan-Ni Meng, Xiao-Jun Duan, Lu Chen, Lin-Rui Li, Yan-Ping Chen
We characterized the expression profile of angiogenesis-related genes (ARG) and matrix metalloproteinase (MMP) genes in preterm infants, with and without bronchopulmonary dysplasia (BPD). We reanalyzed a gene expression dataset for preterm infants from the Gene Expression Omnibus database using the Gene-Cloud of Biotechnology Information platform. A total of 1,652 genes were differentially (1.2-fold change) expressed: 811 were highly expressed in infants with BPD, and 841 were highly expressed in those without BPD...
January 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28099467/senescent-atrophic-epidermis-retains-lrig1-stem-cells-and-loses-wnt-signaling-a-phenotype-shared-with-cd44ko-mice
#15
Laurent Barnes, Jean-Hilaire Saurat, Gürkan Kaya
Lrig1 is known to repress the epidermal growth through its inhibitory activity on EGFR, while CD44 promotes it. We analyzed the expression of these molecules in senescent atrophic human epidermis and in the epidermis of CD44KO mice. In normal human epidermis, Lrig1+ cells form clusters located in the basal layer in which CD44 expression is downregulated and Lef1 expression reflects an active Wnt signaling. In senescent atrophic human epidermis, we found retention of Lrig1high+ cells all along the basal layer, forming no clusters, with decrease of CD44 and lef1 expression...
2017: PloS One
https://www.readbyqxmd.com/read/28098757/role-of-mir-34a-5p-in-hematopoietic-progenitor-cells-proliferation-and-fate-decision-novel-insights-into-the-pathogenesis-of-primary-myelofibrosis
#16
Elisa Bianchi, Samantha Ruberti, Sebastiano Rontauroli, Paola Guglielmelli, Simona Salati, Chiara Rossi, Roberta Zini, Enrico Tagliafico, Alessandro Maria Vannucchi, Rossella Manfredini
Primary Myelofibrosis (PMF) is a chronic Philadelphia-negative myeloproliferative neoplasm characterized by a skewed megakaryopoiesis and an overproduction of proinflammatory and profibrotic mediators that lead to the development of bone marrow (BM) fibrosis. Since we recently uncovered the upregulation of miR-34a-5p in PMF CD34+ hematopoietic progenitor cells (HPCs), in order to elucidate its role in PMF pathogenesis here we unravelled the effects of miR-34a-5p overexpression in HPCs. We showed that enforced expression of miR-34a-5p partially constrains proliferation and favours the megakaryocyte and monocyte/macrophage commitment of HPCs...
January 13, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28065818/growth-retardation-induced-by-avian-leukosis-virus-subgroup-j-associated-with-down-regulated-wnt-%C3%AE-catenin-pathway
#17
Weiguo Feng, Defang Zhou, Wei Meng, Gen Li, Pingping Zhuang, Zhifang Pan, Guihua Wang, Ziqiang Cheng
Avian leukosis virus subgroup J (ALV-J), an oncogenic retrovirus, induces growth retardation and neoplasia in chickens, leading to enormous economic losses in poultry industry. Increasing evidences showed several signal pathways involved in ALV-J infection. However, what signaling pathway involved in growth retardation is largely unknown. To explore the possible signaling pathway, we tested the cell proliferation and associated miRNAs in ALV-J infected CEF cells by CCK-8 and Hiseq, respectively. The results showed that cell proliferation was significantly inhibited by ALV-J and three associated miRNAs were identified to target Wnt/β-catenin pathway...
March 2017: Microbial Pathogenesis
https://www.readbyqxmd.com/read/28043148/analysis-of-differentially-co-expressed-genes-based-on-microarray-data-of-hepatocellular-carcinoma
#18
Y Wang, T Jiang, Z Li, L Lu, R Zhang, D Zhang, X Wang, J Tan
Hepatocellular carcinoma (HCC) is the third leading cause of cancer related death worldwide. Although great progress in diagnosis and management of HCC have been made, the exact molecular mechanisms remain poorly understood. The study aims to identify potential biomarkers for HCC progression, mainly at transcription level. In this study, chip data GSE 29721 was utilized, which contains 10 HCC samples and 10 normal adjacent tissue samples. Differentially expressed genes (DEGs) between two sample types were selected by t-test method...
2017: Neoplasma
https://www.readbyqxmd.com/read/28038713/expression-of-lef1-in-mantle-cell-lymphoma
#19
REVIEW
Dennis P O'Malley, John P Lee, Andrew M Bellizzi
Small lymphocytic lymphoma/chronic lymphocytic leukemia (CLL/SLL) and mantle cell lymphoma (MCL) usually are distinctly different in regard to clinical presentation, morphology, immunophenotype and molecular/genetic findings. In spite of this, select cases may show overlapping characteristics and represent a diagnostic challenge. Recently LEF1 staining was identified as a fairly characteristic finding in CLL/SLL, with positivity identified in up to 95% of cases. LEF1 staining has not been reported as being present in cases of MCL, making this stain a useful tool in distinguishing these diagnoses...
February 2017: Annals of Diagnostic Pathology
https://www.readbyqxmd.com/read/28027119/comparison-of-%C3%AE-catenin-and-lef1-immunohistochemical-stains-in-desmoid-type-fibromatosis-and-its-selected-mimickers-with-unexpected-finding-of-lef1-positivity-in-scars
#20
Youran Zou, Yaxia Zhang, James Church, Xiuli Liu
β-catenin immunohistochemical stain can be useful in the diagnosis of many tumors including desmoid-type fibromatosis (DTF). Lymphoid enhancer-factor 1 (LEF1), a recently emerged marker, is part of the Wnt pathway with β-catenin but has not been studied in DTF. We performed LEF1 and β-catenin immunohistochemistry in DTF (n=26), superficial fibromatosis (n=19), sclerosing mesenteritis (n=12), gastrointestinal stromal tumor (n=17), and cutaneous scar (n=14) using tissue microarray and whole sections. The staining intensity was scored as strong (visible at ×2 objective, value of 3), moderate (visible at ×4, value of 2), weak (visible at ×10, value of 1), and negative (not visible at ×10, value of 0)...
December 23, 2016: Applied Immunohistochemistry & Molecular Morphology: AIMM
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