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Id: biblio-1132553
Autor: Jiang, Tao; Liu, Yingcun; Chen, Biao; Si, Liangyi.
Título: Identification of potential molecular mechanisms and small molecule drugs in myocardial ischemia/reperfusion injury
Fonte: Braz. j. med. biol. res = Rev. bras. pesqui. méd. biol;53(9):0-0, 2020. tab, graf.
Idioma: en.
Resumo: Myocardial ischemia/reperfusion (MI/R) injury is a complex phenomenon that causes severe damage to the myocardium. However, the potential molecular mechanisms of MI/R injury have not been fully clarified. We identified potential molecular mechanisms and therapeutic targets in MI/R injury through analysis of Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were found between MI/R injury and normal samples, and overlapping DEGs were found between GSE61592 and GSE67308. Gene Ontology (GO) and pathway analysis were performed for overlapping DEGs by Database for Annotation, Visualization and Integration Discovery (DAVID). Then, a network of protein-protein interaction (PPI) was constructed through the Search Tool for the Retrieval of Interacting Genes (STRING) database. Potential microRNAs (miRNAs) and therapeutic small molecules were screened out using microRNA.org database and the Comparative Toxicogenomics database (CTD), respectively. Finally, we identified 21 overlapping DEGs related to MI/R injury. These DEGs were significantly enriched in IL-17 signaling pathway, cytosolic DNA-sensing pathway, chemokine signaling, and cytokine-cytokine receptor interaction pathway. According to the degree in the PPI network, CCL2, LCN2, HP, CCL7, HMOX1, CCL4, and S100A8 were found to be hub genes. Furthermore, we identified potential miRNAs (miR-24-3p, miR-26b-5p, miR-2861, miR-217, miR-4251, and miR-124-3p) and therapeutic small molecules like ozone, troglitazone, rosiglitazone, and n-3 polyunsaturated fatty acids for MI/R injury. These results identified hub genes and potential small molecule drugs, which could contribute to the understanding of molecular mechanisms and treatment for MI/R injury.
Descritores: Traumatismo por Reperfusão Miocárdica
MicroRNAs
-Biologia Computacional
Perfilação da Expressão Gênica
Redes Reguladoras de Genes
Mapas de Interação de Proteínas
Ontologia Genética
Responsável: BR1.1 - BIREME


  2 / 25 LILACS  
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Id: biblio-950760
Autor: Ruz, Gonzalo A; Timmermann, Tania; Barrera, Javiera; Goles, Eric.
Título: Neutral space analysis for a Boolean network model of the fission yeast cell cycle network
Fonte: Biol. Res;47:1-12, 2014. ilus, graf, tab.
Idioma: en.
Projeto: CONICYT-Chile; . ANILLO.
Resumo: BACKGROUND: Interactions between genes and their products give rise to complex circuits known as gene regulatory networks (GRN) that enable cells to process information and respond to external stimuli. Several important processes for life, depend of an accurate and context-specific regulation of gene expression, such as the cell cycle, which can be analyzed through its GRN, where deregulation can lead to cancer in animals or a directed regulation could be applied for biotechnological processes using yeast. An approach to study the robustness of GRN is through the neutral space. In this paper, we explore the neutral space of a Schizosaccharomyces pombe (fission yeast) cell cycle network through an evolution strategy to generate a neutral graph, composed of Boolean regulatory networks that share the same state sequences of the fission yeast cell cycle. RESULTS: Through simulations it was found that in the generated neutral graph, the functional networks that are not in the wildtype connected component have in general a Hamming distance more than 3 with the wildtype, and more than 10 between the other disconnected functional networks. Significant differences were found between the functional networks in the connected component of the wildtype network and the rest of the network, not only at a topological level, but also at the state space level, where significant differences in the distribution of the basin of attraction for the G1 fixed point was found for deterministic updating schemes. CONCLUSIONS: In general, functional networks in the wildtype network connected component, can mutate up to no more than 3 times, then they reach a point of no return where the networks leave the connected component of the wildtype. The proposed method to construct a neutral graph is general and can be used to explore the neutral space of other biologically interesting networks, and also formulate new biological hypotheses studying the functional networks in the wildtype network connected component.
Descritores: Schizosaccharomyces/fisiologia
Ciclo Celular/fisiologia
Quinases Ciclina-Dependentes/metabolismo
Redes Reguladoras de Genes/fisiologia
Modelos Biológicos
-Schizosaccharomyces/genética
Gráficos por Computador
Simulação por Computador
Fase G1/fisiologia
Redes Neurais de Computação
Proteínas de Ciclo Celular/metabolismo
Biologia Computacional
Tipo de Publ: Research Support, Non-U.S. Gov't
Responsável: CL1.1 - Biblioteca Central


  3 / 25 LILACS  
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Id: biblio-950831
Autor: Oh, Kimin; Hwang, Taeho; Cha, Kihoon; Yi, Gwan-Su.
Título: Disease association and inter-connectivity analysis of human brain specific co-expressed functional modules
Fonte: Biol. Res;48:1-6, 2015. graf, tab.
Idioma: en.
Projeto: the Ministry of Science; . the Korea government.
Resumo: BACKGROUND: In the recent studies, it is suggested that the analysis of transcriptomic change of functional modules instead of individual genes would be more effective for system-wide identification of cellular functions. This could also provide a new possibility for the better understanding of difference between human and chimpanzee. RESULTS: In this study, we analyzed to find molecular characteristics of human brain functions from the difference of transcriptome between human and chimpanzee's brain using the functional module-centric co-expression analysis. We performed analysis of brain disease association and systems-level connectivity of species-specific co-expressed functional modules. CONCLUSIONS: Throughout the analyses, we found human-specific functional modules and significant overlap between their genes in known brain disease genes, suggesting that human brain disorder could be mediated by the perturbation of modular activities emerged in human brain specialization. In addition, the human-specific modules having neurobiological functions exhibited higher networking than other functional modules. This finding suggests that the expression of neural functions are more connected than other functions, and the resulting high-order brain functions could be identified as a result of consolidated inter-modular gene activities. Our result also showed that the functional module based transcriptome analysis has a potential to expand molecular understanding of high-order complex functions like cognitive abilities and brain disorders.
Descritores: Encéfalo/metabolismo
Pan troglodytes/genética
Redes Reguladoras de Genes/genética
Transcriptoma
Vias Neurais/metabolismo
-Predisposição Genética para Doença/classificação
Predisposição Genética para Doença/genética
Perfilação da Expressão Gênica/métodos
Limites: Humanos
Animais
Tipo de Publ: Research Support, Non-U.S. Gov't
Responsável: CL1.1 - Biblioteca Central


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Id: biblio-1011407
Autor: Yin, Hongtao; Yu, Yan.
Título: Identification of the targets of hematoporphyrin derivative in lung adenocarcinoma using integrated network analysis
Fonte: Biol. Res;52:4, 2019. tab, graf.
Idioma: en.
Resumo: BACKGROUND: Hematoporphyrin derivative (HPD) has a sensibilization effect in lung adenocarcinoma. This study was conducted to identify the target genes of HPD in lung adenocarcinoma. METHODS: RNA sequencing was performed using the lung adenocarcinoma cell line A549 after no treatment or treatment with X-ray or X-ray + HPD. The differentially expressed genes (DEGs) were screened using Mfuzz package by noise-robust soft clustering analysis. Enrichment analysis was carried out using "BioCloud" online tool. Protein-protein interaction (PPI) network and module analyses were performed using Cytoscape software. Using WebGestalt tool and integrated transcription factor platform (ITFP), microRNA target and transcription factor (TF) target pairs were separately predicted. An integrated regulatory network was visualized with Cytoscape software. RESULTS: A total of 815 DEGs in the gene set G1 (continuously dysregulated genes along with changes in processing conditions [untreated-treated with X-ray-X-ray + treated with HPD]) and 464 DEGs in the gene set G2 (significantly dysregulated between X-ray + HPD-treated group and untreated/X-ray-treated group) were screened. The significant module identified from the PPI network for gene set G1 showed that ribosomal protein L3 (RPL3) gene could interact with heat shock protein 90 kDa alpha, class A member 1 (HSP90AA1). TFs AAA domain containing 2 (ATAD2) and protein inhibitor of activated STAT 1 (PIAS1) were separately predicted for the genes in gene set G1 and G2, respectively. In the integrated network for gene set G2, ubiquitin-specific peptidase 25 (USP25) was targeted by miR-200b, miR-200c, and miR-429. CONCLUSION: RPL3, HSP90AA1, ATAD2, and PIAS1 as well as USP25, which is targeted by miR-200b, miR-200c, and miR-429, may be the potential targets of HPD in lung adenocarcinoma.
Descritores: Derivado da Hematoporfirina/farmacologia
Redes Reguladoras de Genes/genética
Adenocarcinoma de Pulmão/genética
Neoplasias Pulmonares/genética
-Proteínas Ribossômicas/efeitos dos fármacos
Proteínas Ribossômicas/genética
Fatores de Transcrição
Análise por Conglomerados
Regulação Neoplásica da Expressão Gênica
Análise de Sequência de RNA
Proteínas de Choque Térmico HSP90/efeitos dos fármacos
Proteínas de Choque Térmico HSP90/genética
Proteínas Modificadoras Pequenas Relacionadas à Ubiquitina/efeitos dos fármacos
Proteínas Modificadoras Pequenas Relacionadas à Ubiquitina/genética
MicroRNAs/metabolismo
Linhagem Celular Tumoral
Proteínas de Ligação a DNA/efeitos dos fármacos
Proteínas de Ligação a DNA/genética
Proteínas Inibidoras de STAT Ativados/efeitos dos fármacos
Proteínas Inibidoras de STAT Ativados/genética
Citometria de Fluxo
ATPases Associadas a Diversas Atividades Celulares/efeitos dos fármacos
ATPases Associadas a Diversas Atividades Celulares/genética
Adenocarcinoma de Pulmão/tratamento farmacológico
Adenocarcinoma de Pulmão/radioterapia
Neoplasias Pulmonares/tratamento farmacológico
Neoplasias Pulmonares/radioterapia
Limites: Humanos
Responsável: CL1.1 - Biblioteca Central


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Id: biblio-889318
Autor: Jiang, Xue; Feng, Lichun; Dai, Baoqiang; Li, Liping; Lu, Weiwei.
Título: Identification of key genes involved in nasopharyngeal carcinoma / Identificação dos principais genes envolvidos no carcinoma nasofaríngeo
Fonte: Braz. j. otorhinolaryngol. (Impr.);83(6):670-676, Nov.-Dec. 2017. tab, graf.
Idioma: en.
Resumo: Abstract Introduction: Nasopharyngeal carcinoma is the most common cancer originating from the nasopharynx. Objective: To study the mechanisms of nasopharyngeal carcinoma, we analyzed GSE12452 microarray data. Methods: GSE12452 was downloaded from the Gene Expression Omnibus database and included 31 nasopharyngeal carcinoma samples and 10 normal nasopharyngeal tissue samples. The differentially expressed genes were screened by ANOVA in the PGS package. Using the BiNGO plugin in Cytoscape and pathway enrichment analysis in the PGS package, functional and pathway enrichment analyses were performed separately to predict potential functions of the differentially expressed genes. Furthermore, Transcription factor-differentially expressed gene pairs were searched, and then the transcription factor-differentially expressed gene regulatory network was visualized using Cytoscape software. Results: A total of 487 genes were screened as differentially expressed genes between the nasopharyngeal carcinoma samples and the normal nasopharyngeal tissue samples. Enrichment analysis indicated that PTGS2 was involved in the regulation of biological process and small cell lung cancer. ZIC2 and OVOL1 may function in nasopharyngeal carcinoma through targeting significantly up-regulated genes (such as PTGS2, FN1, CXCL9 and CXCL10) in the Transcription factor-differentially expressed gene regulatory network (e.g., ZIC2→PTGS2 and OVOL1→CXCL10). Conclusion: PTGS2, FN1, CXCL9, CXCL10, ZIC2 and OVOL1 might play roles in nasopharyngeal carcinoma.

Resumo Introdução: O carcinoma nasofaríngeo é o câncer mais comum originário da nasofaringe. Objetivo: Estudar os mecanismos do câncer de nasofaringe; dados do microarray GSE12452 foram analisados. Método: GSE12452 foi obtido da base de dados Gene Expression Omnibus e inclui 31 amostras de carcinoma nasofaríngeo e 10 amostras de tecido nasofaríngeo normal. Os genes diferencialmente expressos foram analisados por ANOVA no kit PGS. Usando o plugin BiNGO no Cytoscape e análise de enriquecimento da via no kit PGS, análises de enriquecimento funcional e da via foram realizadas separadamente para prever as potenciais funções dos genes diferencialmente expressos. Além disso, os pares Fator de Transcrição - genes diferencialmente expressos foram pesquisados e em seguida a sua rede reguladora foi visualizada usando o programa Cytoscape. Resultados: Um total de 487 genes foram analisados como genes diferencialmente expressos entre as amostras de carcinoma nasofaríngeo e amostras de tecido nasofaríngeo normal. A análise de enriquecimento indicou que PTGS2 estava envolvido na regulação do processo biológico e câncer pulmonar de pequenas células. ZIC2 e OVOL1 podem funcionar no carcinoma nasofaríngeo almejando-se de maneira significativa os genes suprarregulados (como o PTGS2, FN1, CXCL9 e CXCL10) na rede reguladora de fator de transcrição - genes diferencialmente expressos (p.ex., ZIC2→PTGS2 e OVOL1→CXCL10). Conclusão: PTGS2, FN1, CXCL9, CXCL10, ZIC2 e OVOL1 podem desempenhar alguns papéis no carcinoma de nasofaringe.
Descritores: Carcinoma/genética
Expressão Gênica
Neoplasias Nasofaríngeas/genética
-Fatores de Transcrição/genética
Proteínas Nucleares/genética
Carcinoma/patologia
Análise por Conglomerados
Regulação para Baixo
Regulação para Cima
Neoplasias Nasofaríngeas/patologia
Análise de Variância
Perfilação da Expressão Gênica
Bases de Dados Genéticas
Análise em Microsséries
Redes Reguladoras de Genes
Quimiocina CXCL9/genética
Quimiocina CXCL10/genética
Carcinoma Nasofaríngeo
Limites: Humanos
Responsável: BR1.1 - BIREME


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Id: biblio-1087161
Autor: Yin, Ronghuan; Wang, Yanru; Wang, Zeying; Zhu, Yubo; Cong, Yuyan; Wang, Wei; Deng, Liang; Liu, Haiying; Guo, Dan; Bai, Wenlin.
Título: Discovery and molecular analysis of conserved circRNAs from cashmere goat reveal their integrated regulatory network and potential roles in secondary hair follicle
Fonte: Electron. j. biotechnol;41:37-47, sept. 2019. tab, graf, ilus.
Idioma: en.
Projeto: National Natural Science Foundation of China; . Key Project Foundation of Educational Department of Liaoning Province, China; . Innovative Talent Support Program Foundation of Universities and Colleges in Liaoning Province, China; . Science and Technology Innovation Talent Support Foundation for Young and Middle-aged People of Shenyang City, China.
Resumo: Background: Circular RNAs, a novel class in the eukaryotic transcriptome, are characterized by the 3' and 5' ends that are covalently joined in a covalently closed loop without free ends. Circular RNAs are considerably stable molecules and act as microRNA sponges with regulatory potential to the protein-coding genes. Results: Eight circular RNAs were found to be significantly upregulated at anagen skin tissue of cashmere goat compared with their counterparts at telogen. Rich and complex regulatory patterns were revealed among the eight upregulated circular RNAs at anagen and related miRNAs with their potential regulatory genes. The potential regulatory genes of eight upregulated circular RNAs at anagen were involved in several pathways related to the main physiological process of hair follicle, such as histone acetylation and axon. For chi_circ_1926, chi_circ_3541, chi_circ_0483, chi_circ_3196, and chi_circ_2092, overall, the relative expression in secondary hair follicle exhibited highly similar trends with their corresponding host genes during the different stages of the hair follicle cycle. However, the expression trends of chi_circ_0100, chi_circ_2829, and chi_circ_1967 were found to diverge from their corresponding host genes during the different stages of the hair follicle cycle. Conclusions: A total of eighteen circular RNAs were identified and characterized from skin tissue of cashmere goat. The eight upregulated circular RNAs at anagen might have significant roles in the secondary hair follicle of cashmere goat. Our results would provide a novel regulatory layer to elucidate the molecular mechanisms underlying the development of secondary hair follicle and the growth of cashmere fiber in cashmere goat.
Descritores: Cabras/genética
Folículo Piloso/crescimento & desenvolvimento
RNA Circular/genética
-Pele
Expressão Gênica
Biologia Computacional
MicroRNAs
Células Eucarióticas
Redes Reguladoras de Genes
Transcriptoma
RNA Circular/metabolismo
Limites: Animais
Responsável: CL1.1 - Biblioteca Central


  7 / 25 LILACS  
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Id: biblio-1055347
Autor: Camilo, Caroline; Maschietto, Mariana; Vieira, Henrique C; Tahira, Ana C; Gouveia, Gisele R; Feio dos Santos, Ana C; Negrão, André B; Ribeiro, Marcelo; Laranjeira, Ronaldo; Vallada, Homero; Brentani, Helena.
Título: Genome-wide DNA methylation profile in the peripheral blood of cocaine and crack dependents
Fonte: Braz. J. Psychiatry (São Paulo, 1999, Impr.);41(6):485-493, Nov.-Dec. 2019. tab, graf.
Idioma: en.
Projeto: FAPESP; . CAPES; PROEX; . MM and ACT were supported by FAPESP.
Resumo: Objective: Cocaine use disorders (CUDs) represent a major public health problem in many countries. To better understand the interaction between the environmental modulations and phenotype, the aim of the present study was to investigate the DNA methylation pattern of CUD patients, who had concomitant cocaine and crack dependence, and healthy controls. Methods: We studied DNA methylation profiles in the peripheral blood of 23 CUD patients and 24 healthy control subjects using the Illumina Infinium HumanMethylation450 BeadChip arrays. Results: Comparison between CUD patients and controls revealed 186 differentially methylated positions (DMPs; adjusted p-value [adjP] < 10-5) related to 152 genes, with a subset of CpGs confirmed by pyrosequencing. DNA methylation patterns discriminated CUD patients and control groups. A gene network approach showed that the EHMT1, EHMT2, MAPK1, MAPK3, MAP2K1, and HDAC5 genes, which are involved in transcription and chromatin regulation cellular signaling pathways, were also associated with cocaine dependence. Conclusion: The investigation of DNA methylation patterns may contribute to a better understanding of the biological mechanisms involved in CUD.
Descritores: Cocaína Crack
Metilação de DNA
Transtornos Relacionados ao Uso de Cocaína/genética
Transtornos Relacionados ao Uso de Cocaína/sangue
Estudo de Associação Genômica Ampla/métodos
-Estudos de Casos e Controles
Modelos Lineares
Histona-Lisina N-Metiltransferase/genética
Estatísticas não Paramétricas
Proteína Quinase 1 Ativada por Mitógeno/genética
MAP Quinase Quinase 1/genética
Proteína Quinase 3 Ativada por Mitógeno/genética
Redes Reguladoras de Genes
Sequenciamento de Nucleotídeos em Larga Escala
Antígenos de Histocompatibilidade/genética
Histona Desacetilases/genética
Limites: Humanos
Masculino
Adulto
Adulto Jovem
Responsável: BR1.1 - BIREME


  8 / 25 LILACS  
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Id: biblio-1001087
Autor: Tao, Qiu; Tianyu, Wang; Jiangqiao, Zhou; Zhongbao, Chen; Xiaoxiong, Ma; Long, Zhang; Jilin, Zou.
Título: Expression analysis of long non-coding RNAs in a renal ischemia-reperfusion injury model
Fonte: Acta cir. bras;34(4):e201900403, 2019. tab, graf.
Idioma: en.
Projeto: National Natural Science Foundation of China.
Resumo: Abstract Purpose: To investigate the long non-coding RNAs (lncRNAs) profile on renal ischemia reperfusion in a mouse model. Methods: Microarray analysis was used to study the expression of misregulated lncRNA in a mouse model of renal ischemia reperfusion(I/R) with long ischemia time. Quantitative real-time PCR (qPCR) was used to verify the expression of selected lncRNAs and mRNAs.The potential functions of the lncRNA was analyzed by bioinformatics tools and databases. Results: Kidney function was impaired in I/R group compared to the normal group. Analysis showed that a total of 2267 lncRNAs and 2341 messenger RNAs (mRNAs) were significantly expressed in I/R group (≥2.0-fold, p < 0.05).The qPCR result showed that lncRNAs and mRNAs expression were consistent with the microarray analysis. The co-expression network profile analysis based on five validated lncRNAs and 203 interacted mRNAs showed it existed a total of 208 nodes and 333 connections. The GO and KEEG pathway analysis results showed that multiple lncRNAs are involved the mechanism of I/R. Conclusion: Multiple lncRNAs are involved in the mechanism of I/R.These analysis results will help us to further understand the mechanism of I/R and promote the new methods targeted at lncRNA to improve I/R injury.
Descritores: RNA Mensageiro/análise
Traumatismo por Reperfusão/genética
RNA Longo não Codificante/análise
Rim/irrigação sanguínea
-Valores de Referência
Regulação para Baixo
Expressão Gênica
Regulação para Cima
Perfilação da Expressão Gênica
Análise Serial de Tecidos/métodos
Redes Reguladoras de Genes
Reação em Cadeia da Polimerase em Tempo Real
Camundongos Endogâmicos C57BL
Limites: Animais
Ratos
Responsável: BR1.1 - BIREME


  9 / 25 LILACS  
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Id: biblio-1023378
Autor: Hirata, Thiago Dominguez Crespo.
Título: Analysis of the transcriptional regulatory mechanisms mediated by microRNAs in Metabolic Syndrome / Análise dos mecanismos regulatórios transcricionais mediados por microRNAs na Síndrome Metabólica.
Fonte: São Paulo; s.n; 2019. 110 p. graf, tab.
Idioma: en.
Tese: Apresentada a Universidade de São Paulo. Faculdade de Ciências Farmacêuticas para obtenção do grau de Doutor.
Resumo: Metabolic Syndrome (MetS) is a combination of diseases interrelated and associated with increased mortality and risk of cardiovascular events. Among the elucidated molecular mechanisms of MetS, there are several genes regulated by miRNAs - small non-coding RNAs. A large number of transcriptomic studies in public databases integrated with new analysis methods can generate new insights. Therefore, this study aimed to identify circulating miRNAs and their target genes in MetS using a Systems Biology approach. For this, we used GEO-NCBI to download and analyse 26 microarray transcriptome studies of MetS and obesity. After preprocessing, the data underwent differential expression (LIMMA method), gene co-expression (CEMiTool), and enrichment (GSEA, Reactome) analyses. We retrieved a gene expression signature for subcutaneous adipose tissue (SAT) for obese individuals that included 291 consistent differentially expressed genes (DEG). This signature had a positive normalized enrichment score (NES) for adaptive immune system activation responses, and negative NES for metabolic pathways. The consensus co-expression network of SAT revealed 3 communities (CM) of densely interconnected genes. These CMs had a high number of up regulated genes and a consistent positive NES among the studies. The co-expressed genes of these 3 CMs were related to neutrophil degranulation, infiltration of immune system cells, and inflammatory processes. Also, a small brazillian cohort (6 individuals with MetS and 6 controls) underwent a seric miRNA profiling using PCR array. From the 222 miRNAs detected in serum, the differential expression analysis identified 4 upregulated miRNAs (miR-30c-5p, miR-421, miR-542-5p and miR-574) in MetS patients (p<0.01). The integrative miRNAs-mRNAs analysis revealed that the circulating upregulated miRNAs had 12 targets in the SAT, 3 targets in the liver; and no targets in the muscle and blood. Many of these target genes are known modulators of proinflammatory pathways. In conclusion, the use of Systems Biology in the analysis of gene networks and circulating miRNAs identified some potential molecular and pathophysiological mechanisms of the Metabolic Syndrome. The circulating miRNAs identified in this study are potential biomarkers and/or therapeutic targets. However, further studies are needed to validate these miRNAs and their target mRNA

A Síndrome Metabólica (MetS) é um conjunto de doenças inter-relacionadas e associadas ao aumento de mortalidade e risco de eventos cardiovasculares. Entre os mecanismos moleculares elucidados da MetS, existem muitos genes regulados por miRNAs - RNAs pequenos não codificadores. O grande número de estudos transcriptômicos em banco dados públicos integrado a novos métodos de análise podem gerar novas descobertas. Deste modo, o objetivo deste estudo foi identificar miRNAs circulantes e genes alvos na MetS usando a abordagem de Biologia de Sistemas. Para isso, GEO-NCBI foi usado para obter e analisar 26 estudos de transcriptoma por microarray de MetS e obesidade. Após o pré-processamento, realizamos análises de expressão diferencial (método LIMMA), co-expressão gênica (CEMiTool), e enriquecimento (GSEA, Reactome). Identificamos uma assinatura de expressão gênica do tecido adiposo subcutâneo (SAT) de indivíduos obesos, composta por 291 genes consistentemente diferencialmente expressos (DEG). Essa assinatura teve um escore de enriquecimento normalizado (NES) positivo para ativação de respostas do sistema imune adaptativo, e NES negativo para vias de metabolismo. A rede consenso de co-expressão do SAT revelou 3 comunidades (CM) de genes densamente interconectadas. Essas CMs continham muitos genes regulados positivamente e com consistência de NES positivo entre os estudos. Os genes co-expressos dessas 3 comunidades pertenciam a vias de a degranulação de neutrófilos, infiltração de células do sistema imune e processos inflamatórios. Além disso, uma pequena coorte brasileira (6 indivíduos com MetS e 6 controles) foi submetida à dosagem sérica de miRNAs por PCR array. Dos 222 miRNAs detectados no soro, a análise de expressão diferencial identificou 4 miRNAs regulados positivamente (miR-30c-5p, miR-421, miR-542-5p e miR-574) nos pacientes com MetS (p<0.01). A análise integrativa miRNAs-mRNAs revelou que osmiRNAs circulantes superexpressos tinham 12 alvos no SAT, 3 alvos no fígado; e nenhum alvo no músculo e no sangue. Muitos desses alvos são moduladores de vias ró-inflamatórias. Em conclusão, a utilização da Biologia de Sistemas na análise de redes gênicas e miRNAs circulantes identificou alguns potenciais mecanismos moleculares e fisiopatológicos da Síndrome Metabólica. Os miRNAs circulantes identificados neste trabalho são potenciais biomarcadores e/ou alvos terapêuticos. Entretanto, mais estudos são necessários para validar esses miRNAs e seus mRNAs alvos
Descritores: Síndrome Metabólica/diagnóstico
MicroRNAs/análise
Biologia de Sistemas/instrumentação
-RNA Mensageiro/análise
Redes Reguladoras de Genes
Obesidade/classificação
Responsável: BR40.1 - DBD - Divisão de Biblioteca e Documentacão do Conjunto das Químicas
BR40.1; T574.88, H688a. 30100022638-F


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Id: biblio-889107
Autor: Wu, Wei; Huang, Bo; Yan, Yan; Zhong, Zhi-Qiang.
Título: Exploration of gene functions for esophageal squamous cell carcinoma using network-based guilt by association principle
Fonte: Braz. j. med. biol. res = Rev. bras. pesqui. méd. biol;51(6):e6801, 2018. tab, graf.
Idioma: en.
Resumo: Gene networks have been broadly used to predict gene functions based on guilt by association (GBA) principle. Thus, in order to better understand the molecular mechanisms of esophageal squamous cell carcinoma (ESCC), our study was designed to use a network-based GBA method to identify the optimal gene functions for ESCC. To identify genomic bio-signatures for ESCC, microarray data of GSE20347 were first downloaded from a public functional genomics data repository of Gene Expression Omnibus database. Then, differentially expressed genes (DEGs) between ESCC patients and controls were identified using the LIMMA method. Afterwards, construction of differential co-expression network (DCN) was performed relying on DEGs, followed by gene ontology (GO) enrichment analysis based on a known confirmed database and DEGs. Eventually, the optimal gene functions were predicted using GBA algorithm based on the area under the curve (AUC) for each GO term. Overall, 43 DEGs and 67 GO terms were gained for subsequent analysis. GBA predictions demonstrated that 13 GO functions with AUC>0.7 had a good classification ability. Significantly, 6 out of 13 GO terms yielded AUC>0.8, which were determined as the optimal gene functions. Interestingly, there were two GO categories with AUC>0.9, which included cell cycle checkpoint (AUC=0.91648), and mitotic sister chromatid segregation (AUC=0.91597). Our findings highlight the clinical implications of cell cycle checkpoint and mitotic sister chromatid segregation in ESCC progression and provide the molecular foundation for developing therapeutic targets.
Descritores: Carcinoma de Células Escamosas/genética
Biologia Computacional/métodos
Neoplasias Esofágicas/genética
Perfilação da Expressão Gênica/métodos
Regulação Neoplásica da Expressão Gênica/genética
Redes Reguladoras de Genes/genética
-Área Sob a Curva
Limites: Humanos
Responsável: BR1.1 - BIREME



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