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https://www.readbyqxmd.com/read/27811935/integrated-computational-approach-to-the-analysis-of-rna-seq-data-reveals-new-transcriptional-regulators-of-psoriasis
#1
Alena Zolotarenko, Evgeny Chekalin, Alexandre Mesentsev, Ludmila Kiseleva, Elena Gribanova, Rohini Mehta, Ancha Baranova, Tatiana V Tatarinova, Eleonora S Piruzian, Sergey Bruskin
Psoriasis is a common inflammatory skin disease with complex etiology and chronic progression. To provide novel insights into the regulatory molecular mechanisms of the disease, we performed RNA sequencing analysis of 14 pairs of skin samples collected from patients with psoriasis. Subsequent pathway analysis and extraction of the transcriptional regulators governing psoriasis-associated pathways was executed using a combination of the MetaCore Interactome enrichment tool and the cisExpress algorithm, followed by comparison to a set of previously described psoriasis response elements...
November 4, 2016: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/27806296/opposing-development-of-cytotoxic-and-follicular-helper-cd4%C3%A2-t-cells-controlled-by-the-tcf-1-bcl6-nexus
#2
Tiziano Donnarumma, George R Young, Julia Merkenschlager, Urszula Eksmond, Nadine Bongard, Stephen L Nutt, Claude Boyer, Ulf Dittmer, Vu Thuy Khanh Le-Trilling, Mirko Trilling, Wibke Bayer, George Kassiotis
CD4(+) T cells develop distinct and often contrasting helper, regulatory, or cytotoxic activities. Typically a property of CD8(+) T cells, granzyme-mediated cytotoxic T cell (CTL) potential is also exerted by CD4(+) T cells. However, the conditions that induce CD4(+) CTLs are not entirely understood. Using single-cell transcriptional profiling, we uncover a unique signature of Granzyme B (GzmB)(+) CD4(+) CTLs, which distinguishes them from other CD4(+) T helper (Th) cells, including Th1 cells, and strongly contrasts with the follicular helper T (Tfh) cell signature...
November 1, 2016: Cell Reports
https://www.readbyqxmd.com/read/27766570/long-noncoding-rna-tcf7-promotes-invasiveness-and-self-renewal-of-human-non-small-cell-lung-cancer-cells
#3
Jinhui Wu, Dongshuang Wang
Lung cancer is the most common solid tumor and the leading cause of cancer-related death worldwide. Non-small cell lung cancer (NSCLC) represents the major histological subtype and accounts for about 80 % cases of lung cancer cases. Recently, lncRNA lncTCF7 was identified, which is highly expressed in hepatocellular carcinoma (HCC) tumors and liver cancer stem cells (CSCs). However, the role of lnTCF7 in NSCLC remains largely unknown. In this study, Gain- and loss-of-function studies demonstrated the critical role of lncTCF7 in promoting invasion and self-renewal in NSCLC cells...
October 20, 2016: Human Cell
https://www.readbyqxmd.com/read/27764755/icariin-promotes-osteogenic-differentiation-of-rat-bone-marrow-stromal-cells-by-activating-the-er%C3%AE-wnt-%C3%AE-catenin-signaling-pathway
#4
QiuShi Wei, Jin Zhang, GuoJu Hong, ZhenQiu Chen, WeiMin Deng, Wei He, Mei Hui Chen
Icariin, the main effective component of Herba Epimedii, has been identified to regulate the osteogenic differentiation of rat bone marrow stromal cells (rBMSCs) and have potential application in preventing bone loss and promoting bone regeneration. However, the underlying signaling pathway of its osteogenic effect remains unclear. Here, we investigated whether icariin could promote osteogenesis of rBMSCs through modulating the estrogen receptor alpha (ERα) and Wnt/β-catenin signaling pathways, which implicated in rBMSCs osteogenesis...
October 17, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27683056/upregulation-of-mir-192-inhibits-cell-growth-and-invasion-and-induces-cell-apoptosis-by-targeting-tcf7-in-human-osteosarcoma
#5
Yadong Wang, Shanfeng Zhang, Yan Xu, Yan Zhang, Hongya Guan, Xinjie Li, Yuebai Li, Yisheng Wang
MicroRNAs (miRNAs) can function as oncogenes or tumor suppressor genes and are involved in multiple processes in cancer development and progression. For example, miR-192 is dysregulated in multiple human cancers, including osteosarcoma (OS). However, the pathophysiological role of miR-192 and its relevance to OS cell growth and invasion has not yet been clarified. This study aimed to investigate the expression of miR-192 in OS and elucidate the molecular mechanisms by which miR-192 acts as a tumor suppressor in this disease...
September 28, 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/27582468/de-novo-dna-methylation-by-dna-methyltransferase-3a-controls-early-effector-cd8-t-cell-fate-decisions-following-activation
#6
Brian H Ladle, Kun-Po Li, Maggie J Phillips, Alexandra B Pucsek, Azeb Haile, Jonathan D Powell, Elizabeth M Jaffee, David A Hildeman, Christopher J Gamper
DNMT3a is a de novo DNA methyltransferase expressed robustly after T-cell activation that regulates plasticity of CD4(+) T-cell cytokine expression. Here we show that DNMT3a is critical for directing early CD8(+) T-cell effector and memory fate decisions. Whereas effector function of DNMT3a knockout T cells is normal, they develop more memory precursor and fewer terminal effector cells in a T-cell intrinsic manner compared with wild-type animals. Rather than increasing plasticity of differentiated effector CD8(+) T cells, loss of DNMT3a biases differentiation of early effector cells into memory precursor cells...
September 20, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27527215/the-role-of-the-c-clamp-in-wnt-related-colorectal-cancers
#7
REVIEW
Aditi J Ravindranath, Ken M Cadigan
T-cell Factor/Lymphoid Enhancer Factor (TCF/LEF) transcription factors are major regulators of Wnt targets, and the products of the TCF7 and TCF7L2 genes have both been implicated in the progression of colorectal cancer in animal models and humans. TCFs recognize specific DNA sequences through their high mobility group (HMG) domains, but invertebrate TCFs and some isoforms of vertebrate TCF7 and TCF7L2 contain a second DNA binding domain known as the C-clamp. This review will cover the basic properties of C-clamps and their importance in Wnt signaling, using data from Drosophila, C...
2016: Cancers
https://www.readbyqxmd.com/read/27447672/tcf-lef-transcription-factors-an-update-from-the-internet-resources
#8
REVIEW
Dusan Hrckulak, Michal Kolar, Hynek Strnad, Vladimir Korinek
T-cell factor/lymphoid enhancer-binding factor (TCF/LEF) proteins (TCFs) from the High Mobility Group (HMG) box family act as the main downstream effectors of the Wnt signaling pathway. The mammalian TCF/LEF family comprises four nuclear factors designated TCF7, LEF1, TCF7L1, and TCF7L2 (also known as TCF1, LEF1, TCF3, and TCF4, respectively). The proteins display common structural features and are often expressed in overlapping patterns implying their redundancy. Such redundancy was indeed observed in gene targeting studies; however, individual family members also exhibit unique features that are not recapitulated by the related proteins...
July 20, 2016: Cancers
https://www.readbyqxmd.com/read/27259979/gata2-regulates-dendritic-cell-differentiation
#9
Koichi Onodera, Tohru Fujiwara, Yasushi Onishi, Ari Itoh-Nakadai, Yoko Okitsu, Noriko Fukuhara, Kenichi Ishizawa, Ritsuko Shimizu, Masayuki Yamamoto, Hideo Harigae
Dendritic cells (DCs) are critical immune response regulators; however, the mechanism of DC differentiation is not fully understood. Heterozygous germ line GATA2 mutations induce GATA2-deficiency syndrome, characterized by monocytopenia, a predisposition to myelodysplasia/acute myeloid leukemia, and a profoundly reduced DC population, which is associated with increased susceptibility to viral infections, impaired phagocytosis, and decreased cytokine production. To define the role of GATA2 in DC differentiation and function, we studied Gata2 conditional knockout and haploinsufficient mice...
July 28, 2016: Blood
https://www.readbyqxmd.com/read/27152625/a-maternal-system-initiating-the-zygotic-developmental-program-through-combinatorial-repression-in-the-ascidian-embryo
#10
Izumi Oda-Ishii, Atsushi Kubo, Willi Kari, Nobuhiro Suzuki, Ute Rothbächer, Yutaka Satou
Maternal factors initiate the zygotic developmental program in animal embryos. In embryos of the chordate, Ciona intestinalis, three maternal factors-Gata.a, β-catenin, and Zic-r.a-are required to establish three domains of gene expression at the 16-cell stage; the animal hemisphere, vegetal hemisphere, and posterior vegetal domains. Here, we show how the maternal factors establish these domains. First, only β-catenin and its effector transcription factor, Tcf7, are required to establish the vegetal hemisphere domain...
May 2016: PLoS Genetics
https://www.readbyqxmd.com/read/27151989/deletions-of-the-long-arm-of-chromosome-5-define-subgroups-of-t-cell-acute-lymphoblastic-leukemia
#11
Roberta La Starza, Gianluca Barba, Sofie Demeyer, Valentina Pierini, Danika Di Giacomo, Valentina Gianfelici, Claire Schwab, Caterina Matteucci, Carmen Vicente, Jan Cools, Monica Messina, Barbara Crescenzi, Sabina Chiaretti, Robin Foà, Giuseppe Basso, Christine J Harrison, Cristina Mecucci
Recurrent deletions of the long arm of chromosome 5 were detected in 23/200 cases of T-cell acute lymphoblastic leukemia. Genomic studies identified two types of deletions: interstitial and terminal. Interstitial 5q deletions, found in five cases, were present in both adults and children with a female predominance (chi-square, P=0.012). Interestingly, these cases resembled immature/early T-cell precursor acute lymphoblastic leukemia showing significant down-regulation of five out of the ten top differentially expressed genes in this leukemia group, including TCF7 which maps within the 5q31 common deleted region...
August 2016: Haematologica
https://www.readbyqxmd.com/read/27082317/calcitonin-gene-related-peptide-promotes-the-expression-of-osteoblastic-genes-and-activates-the-wnt-signal-transduction-pathway-in-bone-marrow-stromal-stem-cells
#12
Ri Zhou, Zhi Yuan, Jierong Liu, Jian Liu
Calcitonin gene-related peptide (CGRP) is known to induce osteoblastic differentiation and alkaline phosphatase activity in bone marrow stromal stem cells (BMSCs). However, it has remained elusive whether this effect is mediated by CGRP receptors directly or whether other signaling pathways are involved. The present study assessed the possible involvement of the Wnt/β‑catenin signaling pathway in the activation of CGRP signaling during the differentiation of BMSCs. First, the differentiation of BMSCs was induced in vitro and the expression of CGRP receptors was examined by western blot analysis...
June 2016: Molecular Medicine Reports
https://www.readbyqxmd.com/read/26808113/high-density-genotyping-of-immune-related-loci-identifies-new-sle-risk-variants-in-individuals-with-asian-ancestry
#13
Celi Sun, Julio E Molineros, Loren L Looger, Xu-Jie Zhou, Kwangwoo Kim, Yukinori Okada, Jianyang Ma, Yuan-Yuan Qi, Xana Kim-Howard, Prasenjeet Motghare, Krishna Bhattarai, Adam Adler, So-Young Bang, Hye-Soon Lee, Tae-Hwan Kim, Young Mo Kang, Chang-Hee Suh, Won Tae Chung, Yong-Beom Park, Jung-Yoon Choe, Seung Cheol Shim, Yuta Kochi, Akari Suzuki, Michiaki Kubo, Takayuki Sumida, Kazuhiko Yamamoto, Shin-Seok Lee, Young Jin Kim, Bok-Ghee Han, Mikhail Dozmorov, Kenneth M Kaufman, Jonathan D Wren, John B Harley, Nan Shen, Kek Heng Chua, Hong Zhang, Sang-Cheol Bae, Swapan K Nath
Systemic lupus erythematosus (SLE) has a strong but incompletely understood genetic architecture. We conducted an association study with replication in 4,478 SLE cases and 12,656 controls from six East Asian cohorts to identify new SLE susceptibility loci and better localize known loci. We identified ten new loci and confirmed 20 known loci with genome-wide significance. Among the new loci, the most significant locus was GTF2IRD1-GTF2I at 7q11.23 (rs73366469, Pmeta = 3.75 × 10(-117), odds ratio (OR) = 2.38), followed by DEF6, IL12B, TCF7, TERT, CD226, PCNXL3, RASGRP1, SYNGR1 and SIGLEC6...
March 2016: Nature Genetics
https://www.readbyqxmd.com/read/26794868/cross-kingdom-inhibition-of-breast-cancer-growth-by-plant-mir159
#14
Andrew R Chin, Miranda Y Fong, George Somlo, Jun Wu, Piotr Swiderski, Xiwei Wu, Shizhen Emily Wang
MicroRNAs (miRNAs) are critical regulators of gene expression, and exert extensive impacts on development, physiology, and disease of eukaryotes. A high degree of parallelism is found in the molecular basis of miRNA biogenesis and action in plants and animals. Recent studies interestingly suggest a potential cross-kingdom action of plant-derived miRNAs, through dietary intake, in regulating mammalian gene expression. Although the source and scope of plant miRNAs detected in mammalian specimens remain controversial, these initial studies inspired us to determine whether plant miRNAs can be detected in Western human sera and whether these plant miRNAs are able to influence gene expression and cellular processes related to human diseases such as cancer...
February 2016: Cell Research
https://www.readbyqxmd.com/read/26642437/tcf1-links-gipr-signaling-to-the-control-of-beta-cell-function-and-survival
#15
Jonathan E Campbell, John R Ussher, Erin E Mulvihill, Jelena Kolic, Laurie L Baggio, Xiemen Cao, Yu Liu, Benjamin J Lamont, Tsukasa Morii, Catherine J Streutker, Natalia Tamarina, Louis H Philipson, Jeffrey L Wrana, Patrick E MacDonald, Daniel J Drucker
The glucagon-like peptide-1 (GLP-1) receptor and the glucose-dependent insulinotropic polypeptide (GIP) receptor transduce nutrient-stimulated signals to control beta cell function. Although the GLP-1 receptor (GLP-1R) is a validated drug target for diabetes, the importance of the GIP receptor (GIPR) for the function of beta cells remains uncertain. We demonstrate that mice with selective ablation of GIPR in beta cells (MIP-Cre:Gipr(Flox/Flox); Gipr(-/-βCell)) exhibit lower levels of meal-stimulated insulin secretion, decreased expansion of adipose tissue mass and preservation of insulin sensitivity when compared to MIP-Cre controls...
January 2016: Nature Medicine
https://www.readbyqxmd.com/read/26606983/regulatory-network-reconstruction-reveals-genes-with-prognostic-value-for-chronic-lymphocytic-leukemia
#16
Sally Yepes, Maria Mercedes Torres, Liliana López-Kleine
BACKGROUND: The clinical course of chronic lymphocytic leukemia (CLL) is highly variable; some patients follow an indolent course, but others progress to a more advanced stage. The mutational status of rearranged immunoglobulin heavy chain variable (IGVH) genes in CLL is a feature that is widely recognized for dividing patients into groups that are related to their prognoses. However, the regulatory programs associated with the IGVH statuses are poorly understood, and markers that can precisely predict survival outcomes have yet to be identified...
2015: BMC Genomics
https://www.readbyqxmd.com/read/26590303/regulation-of-the-tmepai-promoter-by-tcf7l2-the-c-terminal-tail-of-tcf7l2-is-essential-to-activate-the-tmepai-gene
#17
Naoko Nakano, Mitsuyasu Kato, Susumu Itoh
We previously found that TCF7L2 could activate the TMEPAI gene efficiently, whereas LEF1 could not nearly augment its transcription. When we comprehended the functional difference(s) between TCF7L2 and LEF1 with respect to the activation of the TMEPAI gene, the C-terminal tail of TCF7L2 was needed to reveal its transcriptional activity as well as its interaction with Smad3. Consistently, both TCF7/TCF7L2 and LEF1/TCF7L2 chimeric proteins exhibited an activity similar to TCF7L2 in transcription and Smad3 binding in contrast with LEF1 and TCF7...
January 2016: Journal of Biochemistry
https://www.readbyqxmd.com/read/26578390/identification-of-potential-biomarkers-to-differentially-diagnose-solid-pseudopapillary-tumors-and-pancreatic-malignancies-via-a-gene-regulatory-network
#18
Pengping Li, Yuebing Hu, Jiao Yi, Jie Li, Jie Yang, Jin Wang
BACKGROUND: Solid pseudopapillary neoplasms (SPN) are pancreatic tumors with low malignant potential and good prognosis. However, differential diagnosis between SPN and pancreatic malignancies including pancreatic neuroendocrine tumor (PanNET) and ductal adenocarcinoma (PDAC) is difficult. This study tried to identify candidate biomarkers for the distinction between SPN and the two malignant pancreatic tumors by examining the gene regulatory network of SPN. METHODS: The gene regulatory network for SPN was constructed by a co-expression model...
2015: Journal of Translational Medicine
https://www.readbyqxmd.com/read/26432885/both-ciliary-and-non-ciliary-functions-of-foxj1a-confer-wnt-%C3%AE-catenin-signaling-in-zebrafish-left-right-patterning
#19
Ping Zhu, Xiaolei Xu, Xueying Lin
The Wnt/β-catenin pathway is implicated in left-right (LR) axis determination; however, the underlying mechanism remains elusive. Prompted by our recent discovery that Wnt signaling regulates ciliogenesis in the zebrafish Kupffer's vesicle (KV) via Foxj1a, a ciliogenic transcription factor, we decided to elucidate functions of Foxj1a in Wnt-regulated LR pattern formation. We showed that targeted injection of wnt8a mRNA into a single cell at the 128-cell stage is sufficient to induce ectopic foxj1a expression and ectopic cilia...
2015: Biology Open
https://www.readbyqxmd.com/read/26324778/transcription-factor-7-limits-regulatory-t-cell-generation-in-the-thymus
#20
Melanie M Barra, David M Richards, Jenny Hansson, Ann-Cathrin Hofer, Michael Delacher, Jan Hettinger, Jeroen Krijgsveld, Markus Feuerer
Regulatory T cells (Tregs) differentiate in the thymus, but the mechanisms that control this process are not fully understood. We generated a comprehensive quantitative and differential proteome of murine Tregs and conventional T cells. We identified 5225 proteins, 164 of which were differentially expressed in Tregs. Together with the comparative analysis of proteome and gene expression data, we identified TCF7 as a promising candidate. Genetic elimination of transcription factor 7 (TCF7) led to increased fractions of Tregs in the thymus...
October 1, 2015: Journal of Immunology: Official Journal of the American Association of Immunologists
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