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1.
Medicine (Baltimore) ; 98(38): e17225, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31567982

RESUMO

The present study is to analyze the difference of gene methylation in early cervical adenocarcinoma and to find molecular markers for predicting the occurrence and development of cervical adenocarcinoma.A total of 15 cases of primary cervical adenocarcinoma and 10 cases of primary cervical squamous cell carcinoma at stages IB1 or IIA1 were included in the study. Infinium MethylationEPIC BeadChip (850K) was used to screen specifically expressed genes in cervical adenocarcinoma tissues. Bisulfite sequencing polymerase chain reaction (BSP) and quantitative real-time polymerase chain reaction (qRT-PCR) were used to verify the methylation levels in cervical adenocarcinoma, cervical squamous cell carcinoma, and normal cervical tissues.Sex determining region Y-box 1 (SOX1) and cyclin D1 (CCND1) genes participated in multiple signaling pathways, being the central nodes of gene regulatory networks. SOX1 gene, but not CCND1 gene, was a specifically methylated gene in cervical adenocarcinoma according to BSP. According to qRT-PCR, methylation level of SOX1 in cervical adenocarcinoma tissues is significantly different from that in cervical squamous cell carcinoma tissues or normal cervical tissues, and the methylation level of CCND1 in cervical adenocarcinoma tissues or cervical squamous cell carcinoma tissues is significantly different from that in normal cervical tissues.The present study demonstrates that tumor-suppressor gene SOX1 is a methylation-specific expression gene of cervical adenocarcinoma and is expected to become a specific molecular marker for the diagnosis of cervical adenocarcinoma. However, CCND1 gene was not proven to be a specific methylation expression gene in cervical adenocarcinoma in the present study.


Assuntos
Adenocarcinoma/genética , Metilação de DNA/genética , Fatores de Transcrição SOXB1/genética , Neoplasias do Colo do Útero/genética , Adenocarcinoma/metabolismo , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Colo do Útero/metabolismo , Ciclina D1/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Redes Reguladoras de Genes/genética , Marcadores Genéticos/genética , Humanos , Reação em Cadeia da Polimerase em Tempo Real , Neoplasias do Colo do Útero/metabolismo
2.
Zhonghua Yi Xue Za Zhi ; 99(35): 2761-2767, 2019 Sep 17.
Artigo em Chinês | MEDLINE | ID: mdl-31550799

RESUMO

Objective: To investigate the mechanisms of lncRNA on the occurrence and development of NOA by constructing ceRNA regulation network of lncRNA, miRNA and mRNA. Methods: Samples of adult human testis were obtained from NOA patients and OA patients with normal spermatogenesis (controls), recruited from the Reproductive Medicine Center of Nanfang Hospital from June 2017 to June 2018. Differentially expressed lncRNAs and mRNAs in testicular tissues from patients with NOA were identified by microarray analysis in previous association study. In this study, differentially expressed lncRNAs and mRNA were used to construct the ceRNA regulatory network in NOA and clarify the interaction relationship among lncRNA, miRNA and mRNA. GeneMANIA database was used to construct Protein-Protein Interaction (PPI) of the mRNAs in ceRNA regulatory network. WebGestalt toolkit was employed to perform gene function and pathway enrichment analyses of those coding genes. Finally, qRT-PCR and dual luciferase reporter system were employed for further experimental validation. Results: The ceRNA regulatory network of lncRNA, miRNA and mRNA consists of 21 nodes and 26 edges, of which 4 lncRNAs, 13 miRNAs and 4 mRNAs. 19 proteins were found to interact with the mRNA coding proteins in ceRNA regulatory network by PPI analysis. Gene oncology and KEGG pathway enrichment analyses indicate these coding genes were significantly enriched in pentose metabolic process and pentose phosphate pathway. Furthermore, lncRNA ANXA2P3 was found binding with miR-613 and miR-206 to inhibit mRNA TKT expression. Conclusion: lncRNAs exert an important role in the occurrence and development of NOA via ceRNA regulatory network, which could be used as new biomarkers for NOA treatment.


Assuntos
Azoospermia/genética , Redes Reguladoras de Genes , RNA Longo não Codificante/genética , Humanos , Masculino , MicroRNAs/genética , RNA Mensageiro/genética
3.
Gene ; 720: 144103, 2019 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-31491435

RESUMO

Clear cell renal cell carcinoma (ccRCC) is a highly invasive urological malignant tumor that results in shorter patient survival. At present, the mechanism of ccRCC metastasis is not clear. We explored the possible mechanisms of ccRCC metastasis by analyzing the transcriptome of ccRCC patients from the Cancer Genome Atlas (TCGA) database. Comparing the differences in transcriptome in patients with and without metastasis, we found 323 differential genes (|log2FoldChange| > 1 and P < 0.001). KEGG and GO enrichment analyses of differentially expressed genes (DEGs) suggest that the transfer mechanism of ccRCC may be related to complement and coagulation cascades and cholesterol metabolism. To explore the key genes affecting tumor metastasis, we analyzed the association of these genes with patient survival time and found that 16 genes were significantly associated (P < 0.05). We compared the differences in expression of these 16 genes between ccRCC patients and the normal population, and the results showed that TF and B4GALNT1 were overexpressed in patients. Co-expression gene analysis indicated that TF may participate in the metastasis of cancer through the complement system and mucopolysaccharide biosynthesis. B4GALNT1 may affect metastasis through focal adhesion, calcium signaling pathways, and Hippo signaling pathways. Our studies suggest that the complement system and the coagulation cascade, cholesterol metabolism, calcium pathway and iron transport may be associated in the mechanism of metastasis. TF and B4GALNT1 may be the key genes for metastasis, and they may be potential diagnostic markers and therapeutic targets for ccRCC.


Assuntos
Biomarcadores Tumorais/genética , Carcinoma de Células Renais/genética , Biologia Computacional/métodos , Regulação Neoplásica da Expressão Gênica , Neoplasias Renais/genética , Transcriptoma , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Renais/metabolismo , Carcinoma de Células Renais/secundário , Estudos de Casos e Controles , Feminino , Perfilação da Expressão Gênica , Redes Reguladoras de Genes , Humanos , Neoplasias Renais/metabolismo , Neoplasias Renais/patologia , Masculino , Prognóstico , Mapas de Interação de Proteínas , Transdução de Sinais , Taxa de Sobrevida
4.
Medicine (Baltimore) ; 98(37): e17100, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31517839

RESUMO

BACKGROUND: Tongue squamous cell carcinoma (TSCC) is one of the most common malignant tumors in head and neck, but its molecular mechanism is not clear. METHODS: Weighted gene co-expression network analysis (WGCNA) combining with gene differential expression analysis, survival analysis to screen key modules and hub genes related to the progress of TSCC. Gene Set Enrichment Analysis (GSEA) was used to identify biological pathways that might be involved. RESULTS: Weighted gene co-expression network was constructed based on dataset GSE34105. The blue module and turquoise module most related to the progress of TSCC were identified by the network. Gene Ontology (GO) enrichment analysis showed that 2 key modules were significantly enriched in apoptosis and immunity related biological processes and pathway. Network topology analysis, gene difference analysis and survival analysis were used to screen 9 hub genes (NOC2L, AIMP2, ANXA2, DIABLO, H2AFZ, MANBAL, PRDX6, SNX14, TIMM23). The expression of hub genes was significantly correlated with the prognosis of TSCC. GSEA showed that the high expression group of hub genes was mainly enriched in olfactory transduction, neuroactive ligand receptor interaction, nicotinate and nicotinamide metabolism, and the low expression group was mainly enriched in base excision repair, cysteine and methionine metabolism, oxidative phosphorylation. CONCLUSION: Two key modules and 9 hub genes screened by WGCNA were closely related to the occurrence and prognosis of TSCC. Hub genes can be used as biomarkers and potential therapeutic targets for the accurate diagnosis and treatment of TSCC in the future.


Assuntos
Perfilação da Expressão Gênica/métodos , Redes Reguladoras de Genes , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Neoplasias da Língua/genética , Perfilação da Expressão Gênica/estatística & dados numéricos , Humanos , Modelos Lineares , Prognóstico , Neoplasias da Língua/classificação
5.
BMC Plant Biol ; 19(1): 367, 2019 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-31429697

RESUMO

BACKGROUND: Adaptation to abiotic stresses is crucial for the survival of perennial plants in a natural environment. However, very little is known about the underlying mechanisms. Here, we adopted a liquid culture system to investigate plant adaptation to repeated salt stress in Populus trees. RESULTS: We first evaluated phenotypic responses and found that plants exhibit better stress tolerance after pre-treatment of salt stress. Time-course RNA sequencing (RNA-seq) was then performed to profile changes in gene expression over 12 h of salt treatments. Analysis of differentially expressed genes (DEGs) indicated that significant transcriptional reprogramming and adaptation to repeated salt treatment occurred. Clustering analysis identified two modules of co-expressed genes that were potentially critical for repeated salt stress adaptation, and one key module for salt stress response in general. Gene Ontology (GO) enrichment analysis identified pathways including hormone signaling, cell wall biosynthesis and modification, negative regulation of growth, and epigenetic regulation to be highly enriched in these gene modules. CONCLUSIONS: This study illustrates phenotypic and transcriptional adaptation of Populus trees to salt stress, revealing novel gene modules which are potentially critical for responding and adapting to salt stress.


Assuntos
Adaptação Fisiológica/genética , Regulação da Expressão Gênica de Plantas , Populus/genética , Estresse Salino/genética , Transcrição Genética , Ontologia Genética , Redes Reguladoras de Genes , Genoma de Planta , Fenótipo , Populus/fisiologia , RNA de Plantas , Análise de Sequência de RNA , Transcriptoma , Árvores/genética , Árvores/fisiologia
6.
Mem Inst Oswaldo Cruz ; 114: e190105, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31389522

RESUMO

BACKGROUND: Healthcare-associated infections caused by bacteria such as Pseudomonas aeruginosa are a major public health problem worldwide. Gene regulatory networks (GRN) computationally represent interactions among regulatory genes and their targets. They are an important approach to help understand bacterial behaviour and to provide novel ways of overcoming scientific challenges, including the identification of potential therapeutic targets and the development of new drugs. OBJECTIVES: The goal of this study was to reconstruct the multidrug-resistant (MDR) P. aeruginosa GRN and to analyse its topological properties. METHODS: The methodology used in this study was based on gene orthology inference using the reciprocal best hit method. We used the genome of P. aeruginosa CCBH4851 as the basis of the reconstruction process. This MDR strain is representative of the sequence type 277, which was involved in an endemic outbreak in Brazil. FINDINGS: We obtained a network with a larger number of regulatory genes, target genes and interactions as compared to the previously reported network. Topological analysis results are in accordance with the complex network representation of biological processes. MAIN CONCLUSIONS: The properties of the network were consistent with the biological features of P. aeruginosa. To the best of our knowledge, the P. aeruginosa GRN presented here is the most complete version available to date.


Assuntos
Farmacorresistência Bacteriana Múltipla/genética , Redes Reguladoras de Genes , Pseudomonas aeruginosa/genética , Genoma Bacteriano , Família Multigênica , Infecções por Pseudomonas/genética , Valores de Referência
7.
Microbiol Res ; 227: 126309, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31421713

RESUMO

The phosphorus availability in soil ranged from <0.01 to 1 ppm and found limiting for the utilization by plants. Hence, phosphate solubilizing bacteria (PSB) proficiently fulfill the phosphorus requirement of plants in an eco-friendly manner. The PSB encounter dynamic and challenging environmental conditions viz., high temperature, osmotic, acid, and climatic changes often hamper their activity and proficiency. The modern trend is shifting from isolation of the PSB to their genetic potentials and genome annotation not only for their better performance in the field trials but also to study their ability to cope up with stresses. In order to withstand environmental stress, bacteria need to restructure its metabolic network to ensure its survival. Pi starving condition response regulator (PhoB) and the mediator of stringent stress response alarmone (p)ppGpp known to regulate the global regulatory network of bacteria to provide balanced physiology under various stress condition. The current review discusses the global regulation and crosstalk of genes involved in phosphorus homeostasis, solubilization, and various stress response to fine tune the bacterial physiology. The knowledge of these network crosstalk help bacteria to respond efficiently to the challenging environmental parameters, and their physiological plasticity lead us to develop proficient long-lasting consortia for plant growth promotion.


Assuntos
Fenômenos Fisiológicos Bacterianos , Proteínas de Bactérias/genética , Regulação Bacteriana da Expressão Gênica , Guanosina Pentafosfato/metabolismo , Estresse Fisiológico , Bactérias/genética , Plasticidade Celular , Redes Reguladoras de Genes , Homeostase , Redes e Vias Metabólicas , Anotação de Sequência Molecular , Nitrogênio , Fosfatos/metabolismo , Desenvolvimento Vegetal , Plantas , Solo , Estresse Fisiológico/genética
8.
BMC Plant Biol ; 19(1): 373, 2019 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-31445524

RESUMO

BACKGROUND: The ability of severed rootstocks and shoots to re-establish vascular connections is used to generate grafted plants that combine desirable traits from both scions and rootstocks. Clarifying the mechanisms of graft healing is essential for its further application. We performed RNA sequencing of internodes near the cut position, making a distinction between separated or grafted tissues above and below the cut, in order to obtain a genetic description of graft union formation. RESULTS: Using weighted gene co-expression analysis, variable transcripts were clustered into 10 distinct co-expression networks (modules) based on expression profiles, and genes with the most "hubness" ("hub" genes show the most connections in a network) within each module were predicted. A large proportion of modules were related to Position, and represent asymmetric expression networks from different pathways. Expression of genes involved in auxin and sugar transport and signaling, and brassinosteroid biosynthesis was increased above the cut, while stress response genes were up-regulated below the cut. Some modules were related to graft union formation, among which oxidative detoxification genes were co-expressed along with both wounding response and cell wall organization genes. CONCLUSIONS: The present work provides a comprehensive understanding of graft healing-related gene networks in tomato. Also, the candidate pathways and hub genes identified here will be valuable for future studies of grafting in tomato.


Assuntos
Lycopersicon esculentum/fisiologia , Regeneração/genética , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas , Redes Reguladoras de Genes , Lycopersicon esculentum/genética , Raízes de Plantas/fisiologia , Transdução de Sinais
9.
BMC Bioinformatics ; 20(1): 412, 2019 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-31366320

RESUMO

BACKGROUND: Cartilage damage is a crucial feature involved in several pathological conditions characterized by joint disorders, such as osteoarthritis and rheumatoid arthritis. Accumulated evidences showed that Wnt/ß-catenin pathway plays a role in the pathogenesis of cartilage damage. In addition, it is experimentally documented that lncRNA (long non-coding RNA) HOTAIR plays a key role in the regulation of Wnt/ß-catenin pathway based on directly decreased WIF-1 expression. Further, it is reported that Wnt/ß-catenin pathway is a potent pathway to regulate the expression of MMP-13, which is responsible for degradation of collagen type II in articular cartilage. It is increasingly recognized that systems modeling approach provides an opportunity to understand the complex relationships and direct quantitative analysis of dynamic network in various diseases. RESULTS: A dynamic network of lncRNA HOTAIR-mediated Wnt/ß-catenin pathway regulating MMP-13 is developed to investigate the dynamic mechanism of the network involved in the pathogenesis of cartilage damage. Based on the network modeling, the potential therapeutic intervention point Axin is predicted and confirmed by the experimental validation. CONCLUSIONS: Our study provides a promising strategy for revealing potential dynamic mechanism and assessing potential targets which contribute to the prevention of the pathological conditions related to cartilage damage.


Assuntos
Cartilagem Articular/patologia , Redes Reguladoras de Genes , Terapia de Alvo Molecular , RNA Longo não Codificante/metabolismo , Via de Sinalização Wnt , Proteína Axina/farmacologia , Cartilagem Articular/efeitos dos fármacos , Redes Reguladoras de Genes/efeitos dos fármacos , Humanos , Metaloproteinase 13 da Matriz/metabolismo , Modelos Biológicos , RNA Longo não Codificante/genética , Reprodutibilidade dos Testes , Fatores de Tempo , Via de Sinalização Wnt/efeitos dos fármacos , Via de Sinalização Wnt/genética
10.
Chem Biol Interact ; 311: 108774, 2019 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-31369748

RESUMO

Silica nanoparticles (SiNPs) are one of the popular nanomaterials used in industrial manufacturing, synthesis, engineering, and medicine. Recently, mechanisms underlying toxicity of silica nanoparticles have been reported; however, their uptake mechanisms have still not fully understood. In this study, toxicity of SiNPs was investigated in the nematode Caenohabditis elegans by using microarray and pathway analysis focusing the uptake mechanisms and their impact on toxicity. Physicochemical characterization of SiNPs was performed using dynamic light scattering (DLS) and zeta potential. No mortality was observed after 24 h exposure to SiNPs. However, reproductive ability was significantly reduced at the same concentrations. To ascertain a global mechanism of toxicity, microarray was conducted on C. elegans exposed to 10 mg/L SiNPs (20% reduction in reproductive ability). Microarray results indicated that genes involved in reproduction, such as msp (Major Sperm Protein) genes, were significantly downregulated in C. elegans exposed to SiNPs. Pathway analyses on differentially expressed genes (DEGs) revealed that endocytic pathway as a major pathway involved in the uptake of SiNPs. Involvement of endocytic pathway in the uptake of SiNPs was assessed using specific inhibitors (methyl-ß-cyclodextrin, chlorpromazine, and LY294002 for caveolin-, clathrin-, and pinocytosis-mediated endocytosis, respectively). The inhibitor assay indicated that an internalization process facilitated by clathrin-mediated endocytosis is involved in the uptake of SiNPs. Functional analysis using endocytosis defective mutants, (i,e.  cav-1, cup-2, and chc-1) confirmed the role of endocytosis on the reproductive toxicity of SiNPs. Overall results suggest that clathrin-mediated endocytosis pathway is a potential mechanism of uptake of SiNPs in C. elegans that in turn, affects general toxic outcome, such as, decrease in reproductive ability.


Assuntos
Caenorhabditis elegans/metabolismo , Clatrina/metabolismo , Endocitose/efeitos dos fármacos , Nanopartículas/toxicidade , Dióxido de Silício/química , Animais , Caenorhabditis elegans/crescimento & desenvolvimento , Redes Reguladoras de Genes/efeitos dos fármacos , Nanopartículas/química , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Reprodução/efeitos dos fármacos , beta-Ciclodextrinas/química , beta-Ciclodextrinas/farmacologia
11.
J Agric Food Chem ; 67(35): 9967-9978, 2019 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-31403784

RESUMO

Following the recent completion of the draft genome sequence of the tea plant, high-throughput decoding of gene function, especially for those involved in complex secondary metabolic pathways, has become a major challenge. Here, we profiled the metabolome and transcriptome of 11 tea cultivars, and then illustrated a weighted gene coexpression network analysis (WGCNA)-based system biological strategy to interpret metabolomic flux, predict gene functions, and mine key regulators involved in the flavonoid biosynthesis pathway. We constructed a multilayered regulatory network, which integrated the gene coexpression relationship with the microRNA target and promoter cis-regulatory element information. This allowed us to reveal new uncharacterized TFs (e.g., MADSs, WRKYs, and SBPs) and microRNAs (including 17 conserved and 15 novel microRNAs) that are potentially implicated in different steps of the catechin biosynthesis. Furthermore, we applied metabolic-signature-based association method to capture additional key regulators involved in catechin pathway. This provides important clues for the functional characterization of five SCPL1A acyltransferase family members, which might be implicated in the production balance of anthocyanins, galloylated catechins, and proanthocyanins. Application of an "omics"-based system biology strategy should facilitate germplasm utilization and provide valuable resources for tea quality improvement.


Assuntos
Camellia sinensis/metabolismo , Flavonoides/química , Redes Reguladoras de Genes , Camellia sinensis/química , Camellia sinensis/classificação , Camellia sinensis/genética , Flavonoides/metabolismo , Regulação da Expressão Gênica de Plantas , Metabolômica , Folhas de Planta/química , Folhas de Planta/classificação , Folhas de Planta/genética , Folhas de Planta/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Transcriptoma
12.
Gene ; 720: 144035, 2019 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-31404595

RESUMO

Alcoholic hepatitis (AH) is a severe form of alcoholic liver disease associated with high mortality. Current pharmacological treatment options are not fully effective, and novel target therapies are urgently needed. Until now, key genes, miRNAs and potential signaling pathways in AH remain unclear. Here, we integrated mRNA and miRNA expression profiles to reveal 1411 differentially expressed genes (DEG) and 69 differentially expressed miRNAs (DEM) in AH. And then 51 overlapping genes were identified by compared with miRNA target genes and DEGs, which named as consistent expression genes (CEGs). Pathway analysis showed that CEGs were mainly enriched in PI3K-Akt signaling pathway, MicroRNAs in cancer, FoxO signaling pathway, TNF signaling pathway and P53 signaling pathway. A total of 8 hub genes,FOS, FOXO1, SIRT1, ESR1, BCL2L11, CDK1, CCNB1 and CDKN1A, were screened using protein-protein interaction network analysis. In the regulatory network of miRNA and hub genes, a total of five miRNAs, miR-29c, miR-92b, miR-132, miR-221, miR-222, were identified as key miRNAs. Among them, miR-132 has been shown to target SIRT1, FOXO1, CDKN1A and BCL2L11, and miR-92b targets SIRT1 and BCL2L11. miR-221 and miR-222 both target FOS, ESR1, and BCL2L11. In addition, miR-29c is one of the major down-regulated miRNAs in AH, targeting FOS. Western blot analysis showed that SIRT1 and FoxO1 were expressed at low levels (P < 0.05) and CDK1 was highly expressed in the AH group (P < 0.05). The other five proteins were not significantly different between the two groups (P > 0.05). RT-PCR results showed that miR-132 was significantly higher in the AH group than in the normal group (P < 0.05), while miR-29c was lower than the normal group (P < 0.05), and the other three miRNAs were not significantly different between the two groups (P > 0.05). Therefore, SIRT1, FOXO1, CDK1, miR-132 and miR-29c are involved in the regulation of FoxO and P53 signaling pathways, cell cycle and other biological processes, which may play a key role in the pathogenesis of AH.


Assuntos
Biomarcadores/análise , Biologia Computacional/métodos , Regulação da Expressão Gênica , Redes Reguladoras de Genes , Hepatite Alcoólica/genética , MicroRNAs/genética , Transdução de Sinais , Estudos de Casos e Controles , Feminino , Perfilação da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade
13.
Gene ; 720: 144056, 2019 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-31437466

RESUMO

Repeated implantation failure (RIF) was mainly due to poor endometrium receptivity. Long noncoding RNAs (lncRNAs) could regulate endometrium receptivity and act in competing endogenous RNA (ceRNA) theory. However, the regulatory mechanism of the lncRNA-miRNA-mRNA network in repeated implantation failure (RIF) is unclear. We obtained RIF-related expression profiles of lncRNAs, mRNAs, and miRNAs using mid-secretory endometrial tissue samples from 5 women with RIF and 5 controls by RNA-sequencing. Co-expression analysis revealed that three functional modules were enriched in immune response/inflammation process; two functional modules were enriched in metabolic/ biosynthetic process, and one functional module were enriched in cell cycle pathway. By adding the miRNA data, ceRNA regulatory relationship of each module was reconstructed. The ceRNA network of the whole differentially expressed RNAs revealed 10 hub lncRNAs. Among them, TRG-AS1, SIMM25, and NEAT1 were involved in the module1, module2, and module3, respectively; LNC00511 and SLC26A4-AS1 in the module4; H19 in the module5. The real-time polymerase chain reaction (RT-PCR) results of 15 randomly selected RNAs were consistent with our sequencing data. These can be used as novel potential biomarkers for RIF. Furthermore, they might be involved in endometrium receptivity by acting as ceRNA.


Assuntos
Biomarcadores/metabolismo , Endométrio/metabolismo , Redes Reguladoras de Genes , Genoma Humano , MicroRNAs/genética , RNA Longo não Codificante/genética , RNA Mensageiro/genética , Adulto , Estudos de Casos e Controles , Implantação do Embrião , Endométrio/patologia , Feminino , Fertilização In Vitro , Regulação da Expressão Gênica , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos
14.
Medicine (Baltimore) ; 98(34): e16922, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31441876

RESUMO

BACKGROUND: Circular RNAs (circRNAs) have displayed dysregulated expression in several types of cancer. Nevertheless, their function and underlying mechanisms in cervical cancer remains largely unknown. This study aimed to describe the regulatory mechanisms in cervical cancer. METHODS: We downloaded the circRNAs expression profiles from Gene Expression Omnibus database, and RNAs expression profiles from The Cancer Genome Atlas database. We established a circRNA-miRNA-mRNA and circRNA-miRNA-hubgene network. The interactions between proteins were analyzed using the STRING database and hubgenes were identified using MCODE plugin. Then, we conducted a circRNA-miRNA-hubgenes regulatory module. Functional and pathway enrichment analyses were conducted using R packages "Clusterprofile". RESULTS: Six circRNAs, 15 miRNAs, and 158 mRNAs were identified to construct the ceRNA network of cervical cancer. PPI (protein-protein interaction) network and module analysis identified 7 hubgenes. Then, a circRNA-miRNA-hubgene subnetwork was constructed based on the 1 DEcircRNAs, 3 DEmiRNAs, and 3 DEmRNAs. The KEGG pathway analysis indicated DEmRNAs are involved in progesterone-mediated oocyte maturation, cell cycle, and oocyte meiosis. CONCLUSION: These ceRNAs are critical in the pathogenesis of cervical and may serve as future therapeutic biomarkers.


Assuntos
Regulação Neoplásica da Expressão Gênica/genética , Redes Reguladoras de Genes/genética , RNA/genética , Neoplasias do Colo do Útero/genética , Biomarcadores Tumorais/genética , Feminino , Humanos , Mapas de Interação de Proteínas , RNA/metabolismo
15.
BMC Bioinformatics ; 20(1): 417, 2019 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-31409281

RESUMO

BACKGROUND: The development of high throughput sequencing techniques provides us with the possibilities to obtain large data sets, which capture the effect of dynamic perturbations on cellular processes. However, because of the dynamic nature of these processes, the analysis of the results is challenging. Therefore, there is a great need for bioinformatics tools that address this problem. RESULTS: Here we present DynOVis, a network visualization tool that can capture dynamic dose-over-time effects in biological networks. DynOVis is an integrated work frame of R packages and JavaScript libraries and offers a force-directed graph network style, involving multiple network analysis methods such as degree threshold, but more importantly, it allows for node expression animations as well as a frame-by-frame view of the dynamic exposure. Valuable biological information can be highlighted on the nodes in the network, by the integration of various databases within DynOVis. This information includes pathway-to-gene associations from ConsensusPathDB, disease-to-gene associations from the Comparative Toxicogenomics databases, as well as Entrez gene ID, gene symbol, gene synonyms and gene type from the NCBI database. CONCLUSIONS: DynOVis could be a useful tool to analyse biological networks which have a dynamic nature. It can visualize the dynamic perturbations in biological networks and allows the user to investigate the changes over time. The integrated data from various online databases makes it easy to identify the biological relevance of nodes in the network. With DynOVis we offer a service that is easy to use and does not require any bioinformatics skills to visualize a network.


Assuntos
Redes Reguladoras de Genes , Interface Usuário-Computador , Acetaminofen/farmacologia , Biologia Computacional/métodos , Bases de Dados Factuais , Humanos , NF-kappa B/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética
16.
Genet Sel Evol ; 51(1): 34, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31262251

RESUMO

BACKGROUND: Milk quality in dairy cattle is routinely assessed via analysis of mid-infrared (MIR) spectra; this approach can also be used to predict the milk's cheese-making properties (CMP) and composition. When this method of high-throughput phenotyping is combined with efficient imputations of whole-genome sequence data from cows' genotyping data, it provides a unique and powerful framework with which to carry out genomic analyses. The goal of this study was to use this approach to identify genes and gene networks associated with milk CMP and composition in the Montbéliarde breed. RESULTS: Milk cheese yields, coagulation traits, milk pH and contents of proteins, fatty acids, minerals, citrate, and lactose were predicted from MIR spectra. Thirty-six phenotypes from primiparous Montbéliarde cows (1,442,371 test-day records from 189,817 cows) were adjusted for non-genetic effects and averaged per cow. 50 K genotypes, which were available for a subset of 19,586 cows, were imputed at the sequence level using Run6 of the 1000 Bull Genomes Project (comprising 2333 animals). The individual effects of 8.5 million variants were evaluated in a genome-wide association study (GWAS) which led to the detection of 59 QTL regions, most of which had highly significant effects on CMP and milk composition. The results of the GWAS were further subjected to an association weight matrix and the partial correlation and information theory approach and we identified a set of 736 co-associated genes. Among these, the well-known caseins, PAEP and DGAT1, together with dozens of other genes such as SLC37A1, ALPL, MGST1, SEL1L3, GPT, BRI3BP, SCD, GPAT4, FASN, and ANKH, explained from 12 to 30% of the phenotypic variance of CMP traits. We were further able to identify metabolic pathways (e.g., phosphate and phospholipid metabolism and inorganic anion transport) and key regulator genes, such as PPARA, ASXL3, and bta-mir-200c that are functionally linked to milk composition. CONCLUSIONS: By using an approach that integrated GWAS with network and pathway analyses at the whole-genome sequence level, we propose candidate variants that explain a substantial proportion of the phenotypic variance of CMP traits and could thus be included in genomic evaluation models to improve milk CMP in Montbéliarde cows.


Assuntos
Bovinos/genética , Queijo , Estudo de Associação Genômica Ampla/veterinária , Leite/química , Animais , Simulação por Computador , Conjuntos de Dados como Assunto , Feminino , Regulação da Expressão Gênica , Redes Reguladoras de Genes , Masculino , Locos de Características Quantitativas , Sequenciamento Completo do Genoma/veterinária
17.
J Cancer Res Clin Oncol ; 145(9): 2383-2396, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31280346

RESUMO

PURPOSE: Breast cancer is one of the most common malignancies among females, and its prognosis is affected by a complex network of gene interactions. Weighted gene co-expression network analysis was used to construct free-scale gene co-expression networks and to identify potential biomarkers for breast cancer progression. METHODS: The gene expression profiles of GSE42568 were downloaded from the Gene Expression Omnibus database. RNA-sequencing data and clinical information of breast cancer from TCGA were used for validation. RESULTS: A total of ten modules were established by the average linkage hierarchical clustering. We identified 58 network hub genes in the significant module (R2 = 0.44) and 6 hub genes (AGO2, CDC20, CDCA5, MCM10, MYBL2, and TTK), which were significantly correlated with prognosis. Receiver-operating characteristic curve validated that the mRNA levels of these six genes exhibited excellent diagnostic efficiency in the test data set of GSE42568. RNA-sequencing data from TCGA showed that the expression levels of these six genes were higher in triple-negative tumors. One-way ANOVA suggested that these six genes were upregulated at more advanced stages. The results of independent sample t test indicated that MCM10 and TTK were associated with tumor size, and that AGO2, CDC20, CDCA5, MCM10, and MYBL2 were overexpressed in lymph-node positive breast cancer. CONCLUSIONS: AGO2, CDC20, CDCA5, MCM10, MYBL2, and TTK were identified as candidate biomarkers for further basic and clinical research on breast cancer based on co-expression analysis.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/genética , Redes Reguladoras de Genes , Transcriptoma , Biomarcadores Tumorais/análise , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Análise por Conglomerados , Progressão da Doença , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Redes Reguladoras de Genes/genética , Ensaios de Triagem em Larga Escala , Humanos , Análise em Microsséries , Prognóstico
18.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 48(2): 148-157, 2019 Apr 25.
Artigo em Chinês | MEDLINE | ID: mdl-31309752

RESUMO

OBJECTIVE: To identify the differentially expressed genes (DEGs) in peripheral blood mononuclear cells (PBMC) of patients with hepatocellular carcinoma (HCC) and to analyze their regulatory network. METHODS: The DEGs in PBMCs of HCC patients were screened based on GEO database. The functional enrichment analysis and interaction analysis were carried out for DEGs. MCODE algorithm was used to screen core genes of DEGs, and the mirDIP and starBase online tools were used to predict upstream miRNAs and lncRNAs of the core genes. RESULTS: A total of 265 DEGs with a high credibility were identified, which were mainly enriched in the biological activity, such as regulation of cell proliferation, metabolic regulation, cell communication and signaling, and inflammatory diseases according to Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, and the two analyses were correlated. Four diagnostic candidate genes were identified, including FUS RNA binding protein, C-X-C motif chemokine ligand 8, cullin 1 and RNA polymerase Ⅱ subunit H. Subsequently, 10 miRNAs, 1 lncRNAs and 38 circRNAs were predicted, and finally a lncRNA/circRNA-miRNA-mRNA-pathway regulatory networks was constructed. CONCLUSIONS: The diagnostic candidate genes and its regulatory network in HCC PBMC have been identified based on data mining, which could provide potential tumor biomarkers for early diagnosis and treatment of HCC.


Assuntos
Carcinoma Hepatocelular , Regulação Neoplásica da Expressão Gênica , Leucócitos Mononucleares , Neoplasias Hepáticas , Carcinoma Hepatocelular/fisiopatologia , Redes Reguladoras de Genes , Humanos , Leucócitos Mononucleares/metabolismo , Neoplasias Hepáticas/fisiopatologia
19.
Medicine (Baltimore) ; 98(27): e16225, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31277135

RESUMO

MicroRNAs (miRNAs) play a great contribution to the development of diabetic nephropathy (DN). The aim of this study was to explore potential miRNAs-genes regulatory network and biomarkers for the pathogenesis of DN using bioinformatics methods.Gene expression profiling data related to DN (GSE1009) was obtained from the Gene Expression Omnibus (GEO) database, and then differentially expressed genes (DEGs) between DN patients and normal individuals were screened using GEO2R, followed by a series of bioinformatics analyses, including identifying key genes, conducting pathway enrichment analysis, predicting and identifying key miRNAs, and establishing regulatory relationships between key miRNAs and their target genes.A total of 600 DEGs associated with DN were identified. An additional 7 key DEGs, including 6 downregulated genes, such as vascular endothelial growth factor α (VEGFA) and COL4A5, and 1 upregulated gene (CCL19), were identified in another dataset (GSE30528) from glomeruli samples. Pathway analysis showed that the down- and upregulated DEGs were enriched in 14 and 6 pathways, respectively, with 7 key genes mainly involved in extracellular matrix-receptor interaction, PI3K/Akt signaling, focal adhesion, and Rap1 signaling. The relationships between miRNAs and target genes were constructed, showing that miR-29 targeted COL4A and VEGFA, miR-200 targeted VEGFA, miR-25 targeted ITGAV, and miR-27 targeted EGFR.MiR-29 and miR-200 may play important roles in DN. VEGFA and COL4A5 were targeted by miR-29 and VEGFA by miR-200, which may mediate multiple signaling pathways leading to the pathogenesis and development of DN.


Assuntos
Biologia Computacional/métodos , Nefropatias Diabéticas/genética , Perfilação da Expressão Gênica/métodos , MicroRNAs/genética , Regulação para Cima , Redes Reguladoras de Genes , Humanos , Análise em Microsséries
20.
Medicine (Baltimore) ; 98(27): e16240, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31277141

RESUMO

Osteoarthritis (OA), also known as degenerative arthritis, affects millions of people all over the world. OA occurs when the cartilage wears down over time, which is a worldwide complaint. The aim of this study was to screen and verify hub genes involved in developmental chondrogenesis as well as to explore potential molecular mechanisms.The expression profiles of GSE51812 were downloaded from the Gene Expression Omnibus (GEO) database, which contained 9 samples, including 6-week pre-chondrocytes (PC, 6 independent specimens) and 17-week fetal periarticular resting chondrocytes (RC, 3 independent specimens). The raw data were integrated to obtain differentially expressed genes (DEGs) and were further analyzed with bioinformatics analysis. The Gene Ontology (GO) and pathway enrichment of DEGs were conducted via Database for Annotation, Visualization, and Integrated Discovery (DAVID). The protein-protein interaction (PPI) networks of the DEGs were constructed based on data from the search tool for the retrieval of interacting genes (STRING) database. An intersection figure was provided to show the relationship between the DEGs identified in this study and genes from any existed related studies.A total of 9486 DEGs, including 4821 upregulated genes and 4665 downregulated genes were observed. The top 30 developmental chondrogenesis associated genes were identified, including matrix metalloproteinase (MMP)1, MMP3, MMP13, prostaglandin-endoperoxide synthase 2 (PTGS2), and so on. The majority of DEGs, including PTGS2, CCL20, CHI3L1, LIF, CXCL8, and CXCL12 were intensively enriched in immune-associated biological process terms, including inflammatory, and immune responses. Additionally, the majority of DEGs were mainly enriched in NF-kappa ß (NF-kß) signaling pathway and tumor necrosis factor (TNF) signaling pathway. The hub genes identified in STRING and Cytoscape databases included MMP1, MMP3, MMP13, PTGS2 and so on. Among the top 30 upregulated and downregulated DEGs, there were 15 genes have been reported to be associated with OA or developmental chondrogenesis.This large scale gene expression study observed genes associated with human developmental chondrogenesis and their relative GO function, which may offer opportunities for the research for cartilage tissue engineering and novel insights into the prevention of OA in the near future.


Assuntos
Condrogênese/genética , Biologia Computacional/métodos , Perfilação da Expressão Gênica/métodos , Regulação da Expressão Gênica , Osteoartrite/genética , Biomarcadores/metabolismo , Bases de Dados Genéticas , Ontologia Genética , Redes Reguladoras de Genes , Humanos , Osteoartrite/patologia , Transdução de Sinais
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