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[PMID]:28463415
[Au] Autor:McCullough SD; On DM; Bowers EC
[Ad] Endereço:National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina.
[Ti] Título:Using Chromatin Immunoprecipitation in Toxicology: A Step-by-Step Guide to Increasing Efficiency, Reducing Variability, and Expanding Applications.
[So] Source:Curr Protoc Toxicol;72:3.14.1-3.14.28, 2017 May 02.
[Is] ISSN:1934-9262
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Histone modifications work in concert with DNA methylation to regulate cellular structure, function, and response to environmental stimuli. More than 130 unique histone modifications have been described to date, and chromatin immunoprecipitation (ChIP) allows for the exploration of their associations with the regulatory regions of target genes and other DNA/chromatin-associated proteins across the genome. Many variations of ChIP have been developed in the 30 years since its earliest version came into use, which makes it challenging for users to integrate the procedure into their research programs. Furthermore, the differences in ChIP protocols can confound efforts to increase reproducibility across studies. The streamlined ChIP procedure presented here can be readily applied to samples from a wide range of in vitro studies (cell lines and primary cells) and clinical samples (peripheral leukocytes) in toxicology. We also provide detailed guidance on the optimization of critical protocol parameters, such as chromatin fixation, fragmentation, and immunoprecipitation, to increase efficiency and improve reproducibility. Expanding toxicoepigenetic studies to more readily include histone modifications will facilitate a more comprehensive understanding of the role of the epigenome in environmental exposure effects and the integration of epigenetic data in mechanistic toxicology, adverse outcome pathways, and risk assessment. © 2017 by John Wiley & Sons, Inc.
[Mh] Termos MeSH primário: Imunoprecipitação da Cromatina/métodos
Toxicologia/métodos
[Mh] Termos MeSH secundário: Linhagem Celular
DNA/isolamento & purificação
Epigênese Genética
Redes Reguladoras de Genes
Marcação de Genes
Histonas/metabolismo
Seres Humanos
Leucócitos/química
Peptídeo Hidrolases/química
Reação em Cadeia da Polimerase
Cultura Primária de Células
Reprodutibilidade dos Testes
Sonicação
Toxicologia/normas
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Histones); 9007-49-2 (DNA); EC 3.4.- (Peptide Hydrolases)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170503
[St] Status:MEDLINE
[do] DOI:10.1002/cptx.22


  2 / 14212 MEDLINE  
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[PMID]:29262769
[Au] Autor:Ray S; Hossain SMM; Khatun L; Mukhopadhyay A
[Ad] Endereço:Department of Computer Science and Engineering, Aliah University, Kolkata, 700156, West Bengal, India.
[Ti] Título:A comprehensive analysis on preservation patterns of gene co-expression networks during Alzheimer's disease progression.
[So] Source:BMC Bioinformatics;18(1):579, 2017 Dec 20.
[Is] ISSN:1471-2105
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Alzheimer's disease (AD) is a chronic neuro-degenerative disruption of the brain which involves in large scale transcriptomic variation. The disease does not impact every regions of the brain at the same time, instead it progresses slowly involving somewhat sequential interaction with different regions. Analysis of the expression patterns of the genes in different regions of the brain influenced in AD surely contribute for a enhanced comprehension of AD pathogenesis and shed light on the early characterization of the disease. RESULTS: Here, we have proposed a framework to identify perturbation and preservation characteristics of gene expression patterns across six distinct regions of the brain ("EC", "HIP", "PC", "MTG", "SFG", and "VCX") affected in AD. Co-expression modules were discovered considering a couple of regions at once. These are then analyzed to know the preservation and perturbation characteristics. Different module preservation statistics and a rank aggregation mechanism have been adopted to detect the changes of expression patterns across brain regions. Gene ontology (GO) and pathway based analysis were also carried out to know the biological meaning of preserved and perturbed modules. CONCLUSIONS: In this article, we have extensively studied the preservation patterns of co-expressed modules in six distinct brain regions affected in AD. Some modules are emerged as the most preserved while some others are detected as perturbed between a pair of brain regions. Further investigation on the topological properties of preserved and non-preserved modules reveals a substantial association amongst "betweenness centrality" and "degree" of the involved genes. Our findings may render a deeper realization of the preservation characteristics of gene expression patterns in discrete brain regions affected by AD.
[Mh] Termos MeSH primário: Doença de Alzheimer
Biologia Computacional/métodos
Perfilação da Expressão Gênica/métodos
Redes Reguladoras de Genes/genética
Transcriptoma
[Mh] Termos MeSH secundário: Doença de Alzheimer/genética
Doença de Alzheimer/metabolismo
Doença de Alzheimer/fisiopatologia
Encéfalo/metabolismo
Progressão da Doença
Seres Humanos
Transcriptoma/genética
Transcriptoma/fisiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180306
[Lr] Data última revisão:
180306
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171222
[St] Status:MEDLINE
[do] DOI:10.1186/s12859-017-1946-8


  3 / 14212 MEDLINE  
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[PMID]:29187152
[Au] Autor:Spadafore M; Najarian K; Boyle AP
[Ad] Endereço:University of Michigan Medical School, 1301 Catherine, Ann Arbor, 48109-5624, USA. maxspad@umich.edu.
[Ti] Título:A proximity-based graph clustering method for the identification and application of transcription factor clusters.
[So] Source:BMC Bioinformatics;18(1):530, 2017 Nov 29.
[Is] ISSN:1471-2105
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Transcription factors (TFs) form a complex regulatory network within the cell that is crucial to cell functioning and human health. While methods to establish where a TF binds to DNA are well established, these methods provide no information describing how TFs interact with one another when they do bind. TFs tend to bind the genome in clusters, and current methods to identify these clusters are either limited in scope, unable to detect relationships beyond motif similarity, or not applied to TF-TF interactions. METHODS: Here, we present a proximity-based graph clustering approach to identify TF clusters using either ChIP-seq or motif search data. We use TF co-occurrence to construct a filtered, normalized adjacency matrix and use the Markov Clustering Algorithm to partition the graph while maintaining TF-cluster and cluster-cluster interactions. We then apply our graph structure beyond clustering, using it to increase the accuracy of motif-based TFBS searching for an example TF. RESULTS: We show that our method produces small, manageable clusters that encapsulate many known, experimentally validated transcription factor interactions and that our method is capable of capturing interactions that motif similarity methods might miss. Our graph structure is able to significantly increase the accuracy of motif TFBS searching, demonstrating that the TF-TF connections within the graph correlate with biological TF-TF interactions. CONCLUSION: The interactions identified by our method correspond to biological reality and allow for fast exploration of TF clustering and regulatory dynamics.
[Mh] Termos MeSH primário: Algoritmos
Fatores de Transcrição/metabolismo
[Mh] Termos MeSH secundário: Imunoprecipitação da Cromatina
Análise por Conglomerados
DNA/química
DNA/isolamento & purificação
DNA/metabolismo
Redes Reguladoras de Genes
Seres Humanos
Células K562
Cadeias de Markov
Mapas de Interação de Proteínas/genética
Análise de Sequência de DNA
Fatores de Transcrição/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Transcription Factors); 9007-49-2 (DNA)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180306
[Lr] Data última revisão:
180306
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171201
[St] Status:MEDLINE
[do] DOI:10.1186/s12859-017-1935-y


  4 / 14212 MEDLINE  
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[PMID]:29178844
[Au] Autor:Mcclenny LD; Imani M; Braga-Neto UM
[Ad] Endereço:Electrical and Computer Engineering Department, College Station, Texas, USA. levimcclenny@tamu.edu.
[Ti] Título:BoolFilter: an R package for estimation and identification of partially-observed Boolean dynamical systems.
[So] Source:BMC Bioinformatics;18(1):519, 2017 Nov 25.
[Is] ISSN:1471-2105
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Gene regulatory networks govern the function of key cellular processes, such as control of the cell cycle, response to stress, DNA repair mechanisms, and more. Boolean networks have been used successfully in modeling gene regulatory networks. In the Boolean network model, the transcriptional state of each gene is represented by 0 (inactive) or 1 (active), and the relationship among genes is represented by logical gates updated at discrete time points. However, the Boolean gene states are never observed directly, but only indirectly and incompletely through noisy measurements based on expression technologies such as cDNA microarrays, RNA-Seq, and cell imaging-based assays. The Partially-Observed Boolean Dynamical System (POBDS) signal model is distinct from other deterministic and stochastic Boolean network models in removing the requirement of a directly observable Boolean state vector and allowing uncertainty in the measurement process, addressing the scenario encountered in practice in transcriptomic analysis. RESULTS: BoolFilter is an R package that implements the POBDS model and associated algorithms for state and parameter estimation. It allows the user to estimate the Boolean states, network topology, and measurement parameters from time series of transcriptomic data using exact and approximated (particle) filters, as well as simulate the transcriptomic data for a given Boolean network model. Some of its infrastructure, such as the network interface, is the same as in the previously published R package for Boolean Networks BoolNet, which enhances compatibility and user accessibility to the new package. CONCLUSIONS: We introduce the R package BoolFilter for Partially-Observed Boolean Dynamical Systems (POBDS). The BoolFilter package provides a useful toolbox for the bioinformatics community, with state-of-the-art algorithms for simulation of time series transcriptomic data as well as the inverse process of system identification from data obtained with various expression technologies such as cDNA microarrays, RNA-Seq, and cell imaging-based assays.
[Mh] Termos MeSH primário: Software
[Mh] Termos MeSH secundário: Algoritmos
Perfilação da Expressão Gênica
Redes Reguladoras de Genes
Modelos Biológicos
Interface Usuário-Computador
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180306
[Lr] Data última revisão:
180306
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171128
[St] Status:MEDLINE
[do] DOI:10.1186/s12859-017-1886-3


  5 / 14212 MEDLINE  
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[PMID]:28461445
[Au] Autor:Yamamoto S; Ohnishi M
[Ad] Endereço:Department of Bacteriology I, National Institute of Infectious Diseases, Tokyo, Japan yshouji@nih.go.jp.
[Ti] Título:Glucose-Specific Enzyme IIA of the Phosphoenolpyruvate:Carbohydrate Phosphotransferase System Modulates Chitin Signaling Pathways in Vibrio cholerae.
[So] Source:J Bacteriol;199(18), 2017 09 15.
[Is] ISSN:1098-5530
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:In , the genes required for chitin utilization and natural competence are governed by the chitin-responsive two-component system (TCS) sensor kinase ChiS. In the classical TCS paradigm, a sensor kinase specifically phosphorylates a cognate response regulator to activate gene expression. However, our previous genetic study suggested that ChiS stimulates the non-TCS transcriptional regulator TfoS by using mechanisms distinct from classical phosphorylation reactions (S. Yamamoto, J. Mitobe, T. Ishikawa, S. N. Wai, M. Ohnishi, H. Watanabe, and H. Izumiya, Mol Microbiol 91:326-347, 2014, https://doi.org/10.1111/mmi.12462). TfoS specifically activates the transcription of , encoding a small regulatory RNA essential for competence gene expression. Whether ChiS and TfoS interact directly remains unknown. To determine if other factors mediate the communication between ChiS and TfoS, we isolated transposon mutants that turned off :: expression but possessed intact and genes. We demonstrated an unexpected association of chitin-induced signaling pathways with the glucose-specific enzyme IIA (EIIA ) of the phosphoenolpyruvate:carbohydrate phosphotransferase system (PTS) for carbohydrate uptake and catabolite control of gene expression. Genetic and physiological analyses revealed that dephosphorylated EIIA inactivated natural competence and transcription. Chitin-induced expression of the operon, which is required for chitin transport and catabolism, was also repressed by dephosphorylated EIIA Furthermore, the regulation of and expression by EIIA was dependent on ChiS and intracellular levels of ChiS were not affected by disruption of the gene encoding EIIA These results define a previously unknown connection between the PTS and chitin signaling pathways in and suggest a strategy whereby this bacterium can physiologically adapt to the existing nutrient status. The EIIA protein of the PTS coordinates a wide variety of physiological functions with carbon availability. In this report, we describe an unexpected association of chitin-activated signaling pathways in with EIIA The signaling pathways are governed by the chitin-responsive TCS sensor kinase ChiS and lead to the induction of chitin utilization and natural competence. We show that dephosphorylated EIIA inhibits both signaling pathways in a ChiS-dependent manner. This inhibition is different from classical catabolite repression that is caused by lowered levels of cyclic AMP. This work represents a newly identified connection between the PTS and chitin signaling pathways in and suggests a strategy whereby this bacterium can physiologically adapt to the existing nutrient status.
[Mh] Termos MeSH primário: Quitina/metabolismo
Regulação Bacteriana da Expressão Gênica
Sistema Fosfotransferase de Açúcar do Fosfoenolpiruvato/metabolismo
Transdução de Sinais
Vibrio cholerae/genética
Vibrio cholerae/metabolismo
[Mh] Termos MeSH secundário: Elementos de DNA Transponíveis
Redes Reguladoras de Genes
Mutagênese Insercional
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (DNA Transposable Elements); 1398-61-4 (Chitin); EC 2.7.1.- (Phosphoenolpyruvate Sugar Phosphotransferase System)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:180306
[Lr] Data última revisão:
180306
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170503
[St] Status:MEDLINE


  6 / 14212 MEDLINE  
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[PMID]:29371663
[Au] Autor:Shinozaki Y; Nicolas P; Fernandez-Pozo N; Ma Q; Evanich DJ; Shi Y; Xu Y; Zheng Y; Snyder SI; Martin LBB; Ruiz-May E; Thannhauser TW; Chen K; Domozych DS; Catalá C; Fei Z; Mueller LA; Giovannoni JJ; Rose JKC
[Ad] Endereço:Plant Biology Section, School of Integrative Plant Science, Cornell University, Ithaca, NY, 14853, USA.
[Ti] Título:High-resolution spatiotemporal transcriptome mapping of tomato fruit development and ripening.
[So] Source:Nat Commun;9(1):364, 2018 01 25.
[Is] ISSN:2041-1723
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Tomato (Solanum lycopersicum) is an established model for studying fruit biology; however, most studies of tomato fruit growth and ripening are based on homogenized pericarp, and do not consider the internal tissues, or the expression signatures of individual cell and tissue types. We present a spatiotemporally resolved transcriptome analysis of tomato fruit ontogeny, using laser microdissection (LM) or hand dissection coupled with RNA-Seq analysis. Regulatory and structural gene networks, including families of transcription factors and hormone synthesis and signaling pathways, are defined across tissue and developmental spectra. The ripening program is revealed as comprising gradients of gene expression, initiating in internal tissues then radiating outward, and basipetally along a latitudinal axis. We also identify spatial variations in the patterns of epigenetic control superimposed on ripening gradients. Functional studies elucidate previously masked regulatory phenomena and relationships, including those associated with fruit quality traits, such as texture, color, aroma, and metabolite profiles.
[Mh] Termos MeSH primário: Frutas/genética
Regulação da Expressão Gênica no Desenvolvimento
Regulação da Expressão Gênica de Plantas
Lycopersicon esculentum/genética
Transcriptoma
[Mh] Termos MeSH secundário: Frutas/crescimento & desenvolvimento
Frutas/ultraestrutura
Perfilação da Expressão Gênica/métodos
Redes Reguladoras de Genes
Lycopersicon esculentum/crescimento & desenvolvimento
Microscopia Eletrônica de Transmissão
Proteínas de Plantas/genética
Plantas Geneticamente Modificadas
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, U.S. GOV'T, NON-P.H.S.
[Nm] Nome de substância:
0 (Plant Proteins)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180305
[Lr] Data última revisão:
180305
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180127
[St] Status:MEDLINE
[do] DOI:10.1038/s41467-017-02782-9


  7 / 14212 MEDLINE  
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[PMID]:28460460
[Au] Autor:Valdés-Mora F; Locke WJ; Bandrés E; Gallego-Ortega D; Cejas P; García-Cabezas MA; Colino-Sanguino Y; Feliú J; Del Pulgar TG; Lacal JC
[Ad] Endereço:Histone Variants Group, Epigenetics Research Program, Genomics and Epigenetics Division, Garvan Institute of Medical Research, Sydney, New South Wales, Australia.
[Ti] Título:Clinical relevance of the transcriptional signature regulated by CDC42 in colorectal cancer.
[So] Source:Oncotarget;8(16):26755-26770, 2017 Apr 18.
[Is] ISSN:1949-2553
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:CDC42 is an oncogenic Rho GTPase overexpressed in colorectal cancer (CRC). Although CDC42 has been shown to regulate gene transcription, the specific molecular mechanisms regulating the oncogenic ability of CDC42 remain unknown. Here, we have characterized the transcriptional networks governed by CDC42 in the CRC SW620 cell line using gene expression analysis. Our results establish that several cancer-related signaling pathways, including cell migration and cell proliferation, are regulated by CDC42. This transcriptional signature was validated in two large cohorts of CRC patients and its clinical relevance was also studied. We demonstrate that three CDC42-regulated genes offered a better prognostic value when combined with CDC42 compared to CDC42 alone. In particular, the concordant overexpression of CDC42 and silencing of the putative tumor suppressor gene CACNA2D2 dramatically improved the prognostic value. The CACNA2D2/CDC42 prognostic classifier was further validated in a third CRC cohort as well as in vitro and in vivo CRC models. Altogether, we show that CDC42 has an active oncogenic role in CRC via the transcriptional regulation of multiple cancer-related pathways and that CDC42-mediated silencing of CACNA2D2 is clinically relevant. Our results further support the use of CDC42 specific inhibitors for the treatment of the most aggressive types of CRC.
[Mh] Termos MeSH primário: Neoplasias Colorretais/genética
Neoplasias Colorretais/metabolismo
Regulação Neoplásica da Expressão Gênica
Transcriptoma
Proteína cdc42 de Ligação ao GTP/metabolismo
[Mh] Termos MeSH secundário: Animais
Canais de Cálcio/genética
Linhagem Celular Tumoral
Movimento Celular
Proliferação Celular
Neoplasias Colorretais/diagnóstico
Neoplasias Colorretais/mortalidade
Modelos Animais de Doenças
Feminino
Perfilação da Expressão Gênica
Redes Reguladoras de Genes
Genes Supressores de Tumor
Xenoenxertos
Seres Humanos
Camundongos
Gradação de Tumores
Metástase Neoplásica
Estadiamento de Neoplasias
Prognóstico
Reprodutibilidade dos Testes
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (CACNA2D2 protein, human); 0 (Calcium Channels); EC 3.6.5.2 (cdc42 GTP-Binding Protein)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180305
[Lr] Data última revisão:
180305
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170503
[St] Status:MEDLINE
[do] DOI:10.18632/oncotarget.15815


  8 / 14212 MEDLINE  
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[PMID]:29465556
[Au] Autor:Ni Y; Jiang C
[Ad] Endereço:Department of Spine Surgery.
[Ti] Título:Identification of potential target genes for ankylosing spondylitis treatment.
[So] Source:Medicine (Baltimore);97(8):e9760, 2018 Feb.
[Is] ISSN:1536-5964
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:This study aimed to identify the potential target genes for the treatment of ankylosing spondylitis (AS).Dataset GSE25101 was downloaded from Gene Expression Omnibus, including 16 AS and 16 normal control blood samples. Differentially expressed genes (DEGs) were identified using unmatched t-test in limma package with adjusted P < .05. Gene ontology-biological process (GO-BP) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted using multifaceted analysis tool for human transcriptome. Protein-protein interaction (PPI) network was constructed using STRING and Cytoscape, and module analysis was performed using MCODE plug-in. Webgestal was utilized to predict transcriptional factor (TF)-microRNA-target network and Comparative Toxicogenomics Database (CTD) was applied to predict chemical-target network.A total of 334 DEGs were identified, including 136 upregulated genes and 198 downregulated genes. According to STRING, a PPI network was constructed and 1 significant clustered module was screen out with score = 6.33. MAPK7 (degree = 11) and NDUFS4 (degree = 10) were 2 important nodes in PPI network, and both of them were significantly enriched in cAMP mediated signaling pathway (P = 2.02E-02). MAPK7 could be regulated by NFY. Both MAPK7 and NDUFS4 were 2 potential targets for Indomethacin.MAPK7 and NDUFS4 played important roles in the pathogenesis of AS via cAMP mediated signaling pathway. Both of them could be targeted by Indomethacin.
[Mh] Termos MeSH primário: Proteína Quinase 7 Ativada por Mitógeno/sangue
NADH Desidrogenase/sangue
Mapeamento de Interação de Proteínas/métodos
Mapas de Interação de Proteínas/genética
Espondilite Anquilosante/genética
[Mh] Termos MeSH secundário: Anti-Inflamatórios não Esteroides/farmacologia
Estudos de Casos e Controles
Análise por Conglomerados
Biologia Computacional
Redes Reguladoras de Genes
Seres Humanos
Indometacina/farmacologia
Transdução de Sinais/genética
Espondilite Anquilosante/sangue
Espondilite Anquilosante/tratamento farmacológico
Transcriptoma
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Inflammatory Agents, Non-Steroidal); EC 1.6.5.3 (NDUFS4 protein, human); EC 1.6.99.3 (NADH Dehydrogenase); EC 2.7.11.24 (MAPK7 protein, human); EC 2.7.11.24 (Mitogen-Activated Protein Kinase 7); XXE1CET956 (Indomethacin)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180302
[Lr] Data última revisão:
180302
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:180222
[St] Status:MEDLINE
[do] DOI:10.1097/MD.0000000000009760


  9 / 14212 MEDLINE  
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[PMID]:29459023
[Au] Autor:Shen Y; Feng Y; Chen H; Huang L; Wang F; Bai J; Yang Y; Wang J; Zhao W; Jia Y; Peng Y; Lei X; He A
[Ad] Endereço:Department of Hematology, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
[Ti] Título:Focusing on long non-coding RNA dysregulation in newly diagnosed multiple myeloma.
[So] Source:Life Sci;196:133-142, 2018 Mar 01.
[Is] ISSN:1879-0631
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:AIMS: Multiple myeloma (MM) is an incurable hematological cancer with a higher rate of relapse. Alterations in the function of long non-coding RNAs (lncRNAs) promote the progression and metastasis of cancer. We carry out this study to explore the expression profile of differently expressed lncRNAs in newly diagnosed MM. MAIN METHODS: The Bone marrows we analyzed were obtained from five MM and five IDA patients (serving as controls). Arraystar Human LncRNA Array V4.0 was used to profile expression of lncRNAs and mRNAs. Gene ontology (GO) and pathway analysis were utilized to understand the biological roles of differently expressed genes, while Database for Annotation, Visualization and Integrated Discovery (DAVID) was used for constructing the lncRNA-mRNA co-expression network. Quantitative polymerase chain reaction (qRT-PCR) was performed to confirm the expressions of dysregulated lncRNAs. KEY FINDINGS: Bioinformatic analysis of the lncRNA expression identified >3000 dysregulated lncRNAs (difference ≥ 2-fold) in MM samples. GO and pathway analysis revealed that ECM-receptor and cell cycle pathway-related genes were significantly associated with MM. Four dysregulated lncRNAs were confirmed by qRT-PCR. Among them, the expression of ST3GAL6-AS1, LAMA5-AS1and RP11-175D17.3wereassociated with stage and risk status of MM. On the basis of GEO public database analysis, LAMA5-AS1 was related with an overall survival rate of MM patients. SIGNIFICANCE: These results reveal the feasible functions of lncRNAs in pathogenesis of MM. Further studies are required to explore whether these lncRNAs could serve as candidate therapeutic targets and new molecular biomarkers for MM.
[Mh] Termos MeSH primário: Mieloma Múltiplo/genética
RNA Longo não Codificante/biossíntese
[Mh] Termos MeSH secundário: Adulto
Idoso
Células da Medula Óssea/efeitos dos fármacos
Biologia Computacional
Progressão da Doença
Regulação para Baixo/efeitos dos fármacos
Feminino
Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos
Redes Reguladoras de Genes/efeitos dos fármacos
Seres Humanos
Masculino
Meia-Idade
Mieloma Múltiplo/tratamento farmacológico
Reação em Cadeia da Polimerase
RNA Longo não Codificante/efeitos dos fármacos
RNA Longo não Codificante/genética
RNA Mensageiro/biossíntese
RNA Mensageiro/genética
RNA Neoplásico/biossíntese
RNA Neoplásico/genética
Taxa de Sobrevida
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (RNA, Long Noncoding); 0 (RNA, Messenger); 0 (RNA, Neoplasm)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180226
[Lr] Data última revisão:
180226
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180221
[St] Status:MEDLINE


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[PMID]:29377892
[Au] Autor:Wang LX; Li Y; Chen GZ
[Ad] Endereço:Department of Dermatology, The Affiliated Hospital of Qingdao University, Shandong, China.
[Ti] Título:Network-based co-expression analysis for exploring the potential diagnostic biomarkers of metastatic melanoma.
[So] Source:PLoS One;13(1):e0190447, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Metastatic melanoma is an aggressive skin cancer and is one of the global malignancies with high mortality and morbidity. It is essential to identify and verify diagnostic biomarkers of early metastatic melanoma. Previous studies have systematically assessed protein biomarkers and mRNA-based expression characteristics. However, molecular markers for the early diagnosis of metastatic melanoma have not been identified. To explore potential regulatory targets, we have analyzed the gene microarray expression profiles of malignant melanoma samples by co-expression analysis based on the network approach. The differentially expressed genes (DEGs) were screened by the EdgeR package of R software. A weighted gene co-expression network analysis (WGCNA) was used for the identification of DEGs in the special gene modules and hub genes. Subsequently, a protein-protein interaction network was constructed to extract hub genes associated with gene modules. Finally, twenty-four important hub genes (RASGRP2, IKZF1, CXCR5, LTB, BLK, LINGO3, CCR6, P2RY10, RHOH, JUP, KRT14, PLA2G3, SPRR1A, KRT78, SFN, CLDN4, IL1RN, PKP3, CBLC, KRT16, TMEM79, KLK8, LYPD3 and LYPD5) were treated as valuable factors involved in the immune response and tumor cell development in tumorigenesis. In addition, a transcriptional regulatory network was constructed for these specific modules or hub genes, and a few core transcriptional regulators were found to be mostly associated with our hub genes, including GATA1, STAT1, SP1, and PSG1. In summary, our findings enhance our understanding of the biological process of malignant melanoma metastasis, enabling us to identify specific genes to use for diagnostic and prognostic markers and possibly for targeted therapy.
[Mh] Termos MeSH primário: Perfilação da Expressão Gênica/métodos
Redes Reguladoras de Genes/genética
Melanoma/diagnóstico
Metástase Neoplásica/diagnóstico
[Mh] Termos MeSH secundário: Biomarcadores Tumorais/genética
Regulação Neoplásica da Expressão Gênica/genética
Seres Humanos
Melanoma/genética
Melanoma/metabolismo
Análise de Sequência com Séries de Oligonucleotídeos
Mapas de Interação de Proteínas
RNA Mensageiro/metabolismo
Neoplasias Cutâneas/genética
Software
Fatores de Transcrição/metabolismo
Transcriptoma
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Biomarkers, Tumor); 0 (RNA, Messenger); 0 (Transcription Factors)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180226
[Lr] Data última revisão:
180226
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180130
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0190447



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