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1.
Front Cell Infect Microbiol ; 11: 590874, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33791231

RESUMEN

Gut microbiome alterations may play a paramount role in determining the clinical outcome of clinical COVID-19 with underlying comorbid conditions like T2D, cardiovascular disorders, obesity, etc. Research is warranted to manipulate the profile of gut microbiota in COVID-19 by employing combinatorial approaches such as the use of prebiotics, probiotics and symbiotics. Prediction of gut microbiome alterations in SARS-CoV-2 infection may likely permit the development of effective therapeutic strategies. Novel and targeted interventions by manipulating gut microbiota indeed represent a promising therapeutic approach against COVID-19 immunopathogenesis and associated co-morbidities. The impact of SARS-CoV-2 on host innate immune responses associated with gut microbiome profiling is likely to contribute to the development of key strategies for application and has seldom been attempted, especially in the context of symptomatic as well as asymptomatic COVID-19 disease.


Asunto(s)
/patología , Disbiosis/microbiología , Microbioma Gastrointestinal/inmunología , Tracto Gastrointestinal/microbiología , Inmunidad Innata/inmunología , /biosíntesis , /metabolismo , Bacterias/metabolismo , Enfermedades Cardiovasculares/patología , Diabetes Mellitus Tipo 2/patología , Tracto Gastrointestinal/inmunología , Tracto Gastrointestinal/metabolismo , Expresión Génica/genética , Humanos , Complejo de Antígeno L1 de Leucocito/biosíntesis , Obesidad/patología , Probióticos/farmacología , Índice de Severidad de la Enfermedad
2.
Molecules ; 26(6)2021 Mar 10.
Artículo en Inglés | MEDLINE | ID: mdl-33802064

RESUMEN

Caffeic and dihydrocaffeic acid are relevant microbial catabolites, being described as products from the degradation of different phenolic compounds i.e., hydroxycinnamoyl derivatives, anthocyanins or flavonols. Furthermore, caffeic acid is found both in free and esterified forms in many fruits and in high concentrations in coffee. These phenolic acids may be responsible for a part of the bioactivity associated with the intake of phenolic compounds. With the aim of progressing in the knowledge of the health effects and mechanisms of action of dietary phenolics, the model nematode Caenorhabditis elegans has been used to evaluate the influence of caffeic and dihydrocaffeic acids on lifespan and the oxidative stress resistance. The involvement of different genes and transcription factors related to longevity and stress resistance in the response to these phenolic acids has also been explored. Caffeic acid (CA, 200 µM) and dihydrocaffeic acid (DHCA, 300 µM) induced an increase in the survival rate of C. elegans under thermal stress. Both compounds also increased the mean and maximum lifespan of the nematode, compared to untreated worms. In general, treatment with these acids led to a reduction in intracellular ROS concentrations, although not always significant. Results of gene expression studies conducted by RT-qPCR showed that the favorable effects of CA and DHCA on oxidative stress and longevity involve the activation of several genes related to insulin/IGF-1 pathway, such as daf-16, daf-18, hsf-1 and sod-3, as well as a sirtuin gene (sir-2.1).


Asunto(s)
Ácidos Cafeicos/farmacología , Estrés Fisiológico/efectos de los fármacos , Animales , Antioxidantes/farmacología , Caenorhabditis elegans/efectos de los fármacos , Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/efectos de los fármacos , Proteínas de Caenorhabditis elegans/metabolismo , Ácidos Cafeicos/metabolismo , Expresión Génica/efectos de los fármacos , Expresión Génica/genética , Longevidad/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Estrés Fisiológico/genética , Factores de Transcripción/efectos de los fármacos
3.
Mol Cell ; 81(8): 1631-1639, 2021 04 15.
Artículo en Inglés | MEDLINE | ID: mdl-33826920

RESUMEN

Spatial transcriptional profiling provides gene expression information within the important anatomical context of tissue architecture. This approach is well suited to characterizing solid tumors, which develop within a complex landscape of malignant cells, immune cells, and stroma. In a single assay, spatial transcriptional profiling can interrogate the role of spatial relationships among these cell populations as well as reveal spatial patterns of relevant oncogenic genetic events. The broad utility of this approach is reflected in the array of strategies that have been developed for its implementation as well as in the recent commercial development of several profiling platforms. The flexibility to apply these technologies to both hypothesis-driven and discovery-driven studies allows widespread applicability in research settings. This review discusses available technologies for spatial transcriptional profiling and several applications for their use in cancer research.


Asunto(s)
Perfilación de la Expresión Génica/métodos , Neoplasias/genética , Transcripción Genética/genética , Animales , Expresión Génica/genética , Humanos
4.
Am J Hum Genet ; 108(4): 669-681, 2021 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-33730541

RESUMEN

Tests of association between a phenotype and a set of genes in a biological pathway can provide insights into the genetic architecture of complex phenotypes beyond those obtained from single-variant or single-gene association analysis. However, most existing gene set tests have limited power to detect gene set-phenotype association when a small fraction of the genes are associated with the phenotype and cannot identify the potentially "active" genes that might drive a gene set-based association. To address these issues, we have developed Gene set analysis Association Using Sparse Signals (GAUSS), a method for gene set association analysis that requires only GWAS summary statistics. For each significantly associated gene set, GAUSS identifies the subset of genes that have the maximal evidence of association and can best account for the gene set association. Using pre-computed correlation structure among test statistics from a reference panel, our p value calculation is substantially faster than other permutation- or simulation-based approaches. In simulations with varying proportions of causal genes, we find that GAUSS effectively controls type 1 error rate and has greater power than several existing methods, particularly when a small proportion of genes account for the gene set signal. Using GAUSS, we analyzed UK Biobank GWAS summary statistics for 10,679 gene sets and 1,403 binary phenotypes. We found that GAUSS is scalable and identified 13,466 phenotype and gene set association pairs. Within these gene sets, we identify an average of 17.2 (max = 405) genes that underlie these gene set associations.


Asunto(s)
Bancos de Muestras Biológicas , Interpretación Estadística de Datos , Bases de Datos Genéticas , Conjuntos de Datos como Asunto , Estudio de Asociación del Genoma Completo/métodos , Fenotipo , Transportadoras de Casetes de Unión a ATP/genética , Simulación por Computador , Expresión Génica/genética , Humanos , Proyectos de Investigación , Factores de Tiempo , Reino Unido , Navegador Web
5.
DNA Cell Biol ; 40(4): 568-579, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33651959

RESUMEN

The aim of this study was to explore the effects of atrial fibrillation (AF)-derived exosome delivery of miR-107 to human umbilical vein endothelial cells (HUVECs) and its related mechanisms. Exosomes were isolated from the plasma of patients with AF and healthy controls, followed by characterization. The expression levels of miR-320d, miR-103a-3p, and miR-107 were measured using real-time quantitative PCR (RT-qPCR). The dual-luciferase reporter gene was used to verify the downstream target of miR-107. Afterward, HUVECs were treated with AF-derived exosomes or transfected with miR-107 mimics. After cell culture, Cell Counting Kit-8, Transwell, and flow cytometry were used to determine cell viability, migration, and apoptosis and cell cycle phase. Finally, RT-qPCR was performed to examine the expression of related genes. NanoSight, transmission electron microscopy, and western blotting showed that exosomes were successfully isolated, and that AF-derived exosomes could be taken up by HUVECs. The expression of miR-107 was significantly higher in AF-derived exosomes than in normal exosomes (p < 0.05). USP14 was shown to be the direct target of miR-107. In addition, miR-107 mimics and AF-derived exosomes significantly suppressed cell viability and migration (p < 0.05) and enhanced cell apoptosis; they also increased G0/G1-phase cells and reduced S-phase cells. RT-qPCR showed that exosomal miR-107 overexpression significantly downregulated the expression of USP14 and Bcl2 (p < 0.05), whereas it markedly upregulated the expression of ERK2, FAK, and Bax (p < 0.05). AF-derived exosomes can deliver miR-107 to HUVECs, and exosomal miR-107 may regulate cell viability, migration, and apoptosis and cell cycle progression by mediating the miR-107/USP14 pathway.


Asunto(s)
Fibrilación Atrial/genética , Exosomas/genética , MicroARNs/genética , Apoptosis/genética , Fibrilación Atrial/metabolismo , Movimiento Celular/genética , Proliferación Celular/genética , Supervivencia Celular/genética , Expresión Génica/genética , Regulación de la Expresión Génica/genética , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Humanos , MicroARNs/metabolismo
6.
DNA Cell Biol ; 40(4): 580-588, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33761271

RESUMEN

The fall armyworm (Spodoptera frugiperda) is one of the most significant agricultural pests in the world and invaded China in early 2019. We sampled and sequenced RNA-seq data from 15 individuals across different developmental stages. Developmental stages were the larval stage (5th instar larvae and 6th instar larvae), chrysalis stage, and adult stage (female adult and male adult). Individual samples were mainly clustered by developmental stages and we then identified variation between developmental stages of differentially expressed transcripts (DETs). There were 2136 upregulated DETs and 1391 downregulated DETs in the larval stage when comparing larval and chrysalis stages. In the comparison between the chrysalis and adult stages, there were 2033 upregulated DETs and 1391 downregulated DETs in the chrysalis stage. In total, 19,195 abundantly expressed transcripts were obtained and 10% of them were DETs. We then obtained stage-specific DETs to investigate the potential function of the fall armyworm during different developmental stages. We also constructed our annotation background set for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. This indicated that the fall armyworm may undergo active metabolism during its lifespan, even in the chrysalis stage. And it also may experience detoxifying and xenobiotic metabolism throughout its life, especially in the larval stage, which partially explains the difficulty to eradicate using chemical control. Our study is the first insight into the developmental patterns of the fall armyworm and we also provide the fundamental information about enhanced drug resistance at the level of transcriptome. These results are beneficial for a future investigation related to the eradication and/or control stage.


Asunto(s)
Regulación del Desarrollo de la Expresión Génica/genética , Spodoptera/genética , Transcriptoma/genética , Animales , China , Expresión Génica/genética , Ontología de Genes , Larva/genética , RNA-Seq/métodos , Spodoptera/embriología
7.
DNA Cell Biol ; 40(4): 595-605, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33769863

RESUMEN

Canine distemper (CD) is a significant threat to wild and captive giant panda populations. Captive giant pandas are inoculated with canine distemper virus (CDV) vaccination to prevent the infection with the CDV. As an important regulator, microRNA (miRNA) plays a crucial role in regulating gene expression, including in disease immunity. To understand the role of miRNA in immune response to CDV vaccination, we investigated the miRNA expression profile in five giant panda cubs after two inoculations, 21 days apart. A total of 187 conserved miRNAs and 96 novel miRNAs were identified. Among the 187 conserved miRNAs, 29 differentially expressed miRNAs were found postinoculation. The upregulation of miR-16, miR-182, miR-30b, and miR-101 indicated that the innate immune may be enhanced, whereas the upregulation of miR-142 and miR-19a are probably involved in the enhanced cellular immune response. However, the downregulated miR-155 and miR-181a might indicate the giant panda has weak ability to produce antibodies and memory B cells. Integrated analysis of miRNA-messenger RNA (mRNA) found 20 negatively regulated miRNA-mRNA pairs, where downregulated miR-204 might enhance giant panda cub innate immunity by increasing TLR6 expression, and downregulated miR-330 might activate macrophages and regulate the immune response by increasing TMEM106A expression. Our research provides key information for future development to enhance the immune response of giant pandas and potentially improve the survival of captive and wild giant panda populations threatened by CD.


Asunto(s)
Moquillo/tratamiento farmacológico , MicroARNs/genética , Ursidae/genética , Animales , China , Moquillo/virología , Virus del Moquillo Canino/genética , Virus del Moquillo Canino/inmunología , Virus del Moquillo Canino/patogenicidad , Expresión Génica/genética , Perfilación de la Expresión Génica/métodos , Inmunidad Innata/genética , MicroARNs/efectos de los fármacos , ARN Mensajero/metabolismo , Transcriptoma/genética , Vacunación/métodos , Vacunación/veterinaria
8.
EBioMedicine ; 65: 103262, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33691247

RESUMEN

BACKGROUND: The coronavirus disease-19 (COVID-19) pandemic has cost lives and economic hardships globally. Various studies have found a number of different factors, such as hyperinflammation and exhausted/suppressed T cell responses to the etiological SARS coronavirus-2 (SARS-CoV-2), being associated with severe COVID-19. However, sieving the causative from associative factors of respiratory dysfunction has remained rudimentary. METHODS: We postulated that the host responses causative of respiratory dysfunction would track most closely with disease progression and resolution and thus be differentiated from other factors that are statistically associated with but not causative of severe COVID-19. To track the temporal dynamics of the host responses involved, we examined the changes in gene expression in whole blood of 6 severe and 4 non-severe COVID-19 patients across 15 different timepoints spanning the nadir of respiratory function. FINDINGS: We found that neutrophil activation but not type I interferon signaling transcripts tracked most closely with disease progression and resolution. Moreover, transcripts encoding for protein phosphorylation, particularly the serine-threonine kinases, many of which have known T cell proliferation and activation functions, were increased after and may thus contribute to the upswing of respiratory function. Notably, these associative genes were targeted by dexamethasone, but not methylprednisolone, which is consistent with efficacy outcomes in clinical trials. INTERPRETATION: Our findings suggest neutrophil activation as a critical factor of respiratory dysfunction in COVID-19. Drugs that target this pathway could be potentially repurposed for the treatment of severe COVID-19. FUNDING: This study was sponsored in part by a generous gift from The Hour Glass. EEO and JGL are funded by the National Medical Research Council of Singapore, through the Clinician Scientist Awards awarded by the National Research Foundation of Singapore.


Asunto(s)
/patología , Activación de Linfocitos/inmunología , Activación Neutrófila/inmunología , /inmunología , Adulto , Anciano , Progresión de la Enfermedad , Reposicionamiento de Medicamentos , Femenino , Expresión Génica/genética , Perfilación de la Expresión Génica , Humanos , Masculino , Persona de Mediana Edad , Neutrófilos/inmunología , Estudios Prospectivos , Linfocitos T/inmunología
9.
Nat Commun ; 12(1): 1609, 2021 03 11.
Artículo en Inglés | MEDLINE | ID: mdl-33707455

RESUMEN

Histopathological images are used to characterize complex phenotypes such as tumor stage. Our goal is to associate features of stained tissue images with high-dimensional genomic markers. We use convolutional autoencoders and sparse canonical correlation analysis (CCA) on paired histological images and bulk gene expression to identify subsets of genes whose expression levels in a tissue sample correlate with subsets of morphological features from the corresponding sample image. We apply our approach, ImageCCA, to two TCGA data sets, and find gene sets associated with the structure of the extracellular matrix and cell wall infrastructure, implicating uncharacterized genes in extracellular processes. We find sets of genes associated with specific cell types, including neuronal cells and cells of the immune system. We apply ImageCCA to the GTEx v6 data, and find image features that capture population variation in thyroid and in colon tissues associated with genetic variants (image morphology QTLs, or imQTLs), suggesting that genetic variation regulates population variation in tissue morphological traits.


Asunto(s)
Biología Computacional/métodos , Regulación Neoplásica de la Expresión Génica/genética , Expresión Génica/genética , Neoplasias/patología , Sitios de Carácter Cuantitativo/genética , Proteína BRCA1/genética , Biomarcadores de Tumor/genética , Membrana Celular/genética , Membrana Celular/fisiología , Matriz Extracelular/genética , Matriz Extracelular/fisiología , Humanos , Procesamiento de Imagen Asistido por Computador , Neoplasias/genética , Polimorfismo de Nucleótido Simple/genética
10.
Medicine (Baltimore) ; 100(12): e25093, 2021 Mar 26.
Artículo en Inglés | MEDLINE | ID: mdl-33761671

RESUMEN

ABSTRACT: Based on the Thompson classification of intervertebral discs (IVDs), we systematically analyzed gene expression differences between severely degenerated and mildly degenerated IVDs and explored the underlying molecular mechanisms using bioinformatics methods and multichip integration. We used multiomics analysis, includes mRNA microarray and methylation chips, to explore the genetic network and mechanisms of lumbar disc herniation (LDH). Subsequently, the Combat function of the R language SVA package was applied to eliminate heterogeneity between the gene expression data. And the protein-protein interaction (PPI) network, gene ontology (GO), and molecular pathways were used to constructs the mechanisms network. Consequently, we obtained 149 differentially expressed genes. Related molecular pathways are the following: ribosome activity, oxidative phosphorylation, extracellular matrix response. Besides, through PPI network analysis, genes with higher connectivity such as UBA52, RPLP0, RPL3, RPLP2, and RPL27 were also identified, suggesting that they play important regulatory roles in the complex network associated with LDH. Additionally, cg12556991 (RPL27) and cg06852319 (RPLP0) were found to be LDH-related candidate DNA methylation modification sites in the IVDs tissue of LDH patients. In conclusions, ribosome activity, oxidative phosphorylation, and extracellular matrix response may be potential molecular mechanisms underlying LDH, while hub genes involved in UBA52, RPLP0, RPL3, RPLP2, and RPL27, and candidate DNA methylation modification sites of cg12556991and cg06852319 are likely key regulators in the development of LDH.


Asunto(s)
Metilación de ADN/genética , Matriz Extracelular/genética , Desplazamiento del Disco Intervertebral/genética , Fosforilación/genética , Proteínas Ribosómicas/genética , Biología Computacional , Expresión Génica/genética , Perfilación de la Expresión Génica , Ontología de Genes , Redes Reguladoras de Genes/genética , Humanos , Vértebras Lumbares/metabolismo , Análisis por Micromatrices , Mapas de Interacción de Proteínas/genética , ARN Mensajero/metabolismo
11.
Nat Commun ; 12(1): 1437, 2021 03 04.
Artículo en Inglés | MEDLINE | ID: mdl-33664255

RESUMEN

Biosensors are key components in engineered biological systems, providing a means of measuring and acting upon the large biochemical space in living cells. However, generating small molecule sensing elements and integrating them into in vivo biosensors have been challenging. Here, using aptamer-coupled ribozyme libraries and a ribozyme regeneration method, de novo rapid in vitro evolution of RNA biosensors (DRIVER) enables multiplexed discovery of biosensors. With DRIVER and high-throughput characterization (CleaveSeq) fully automated on liquid-handling systems, we identify and validate biosensors against six small molecules, including five for which no aptamers were previously found. DRIVER-evolved biosensors are applied directly to regulate gene expression in yeast, displaying activation ratios up to 33-fold. DRIVER biosensors are also applied in detecting metabolite production from a multi-enzyme biosynthetic pathway. This work demonstrates DRIVER as a scalable pipeline for engineering de novo biosensors with wide-ranging applications in biomanufacturing, diagnostics, therapeutics, and synthetic biology.


Asunto(s)
Aptámeros de Nucleótidos/química , Técnicas Biosensibles/métodos , ARN Catalítico/química , Biología Sintética/métodos , Expresión Génica/genética , Proteínas Fluorescentes Verdes/metabolismo , Ingeniería Metabólica/métodos , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo
12.
Life Sci ; 270: 119140, 2021 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-33524420

RESUMEN

AIMS: Intra-platelet 5-HT (IP 5-HT) and YAP exhibit an important role in hepatocellular carcinoma (HCC). The aim of the study was to investigate whether IP 5-HT and YAP could affect the progression and prognosis of HCC. METHODS: 5-HT level and YAP expression were measured and were compared between HCC patients and control patients. By grouping HCC patients, we analyzed clinical indicators and survival. The predictive nomogram was established by R software according to the risk factors obtained from multivariate analysis. RESULTS: Higher IP 5-HT level and higher YAP expression were associated with poorer prognosis. In addition, they were also associated with BCLC stages. Higher IP 5-HT was found to be related with higher international normalized ratio (INR) (p = 0.040), more death (p = 0.015) and higher YAP expression (p < 0.001). Similarly, higher YAP expression was proved to be associated with lower platelet counts (PLT) (p = 0.032), smaller tumor size (p = 0.017), more death (p < 0.001) and higher IP 5-HT (p < 0.001). In addition, alkaline phosphatase (ALP), YAP and tumor size were proved to be independent risk factors. By using risk factors, we have established a prognostic prediction nomogram for HCC patients. In the prognostic prediction nomogram, patients with higher scores would have poorer prognosis. CONCLUSIONS: IP 5-HT and YAP might affect the progression and prognosis of HCC through synergistic effect. Moreover, IP 5-HT might affect HCC by regulating YAP expression. Thus, both of them might be potential therapeutic targets. By establishing the prognostic prediction nomogram, we could improve the prediction system.


Asunto(s)
Plaquetas/metabolismo , Carcinoma Hepatocelular/metabolismo , Proteínas de Ciclo Celular/metabolismo , Serotonina/metabolismo , Factores de Transcripción/metabolismo , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Adulto , Biomarcadores de Tumor/metabolismo , Carcinoma Hepatocelular/patología , Proteínas de Ciclo Celular/análisis , Proteínas de Ciclo Celular/sangre , Femenino , Expresión Génica/genética , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patología , Masculino , Persona de Mediana Edad , Nomogramas , Fosfoproteínas/metabolismo , Pronóstico , Serotonina/análisis , Serotonina/sangre , Factores de Transcripción/análisis , Factores de Transcripción/sangre , Transcriptoma/genética
13.
Life Sci ; 270: 119158, 2021 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-33545200

RESUMEN

AIMS: Malaria is a serious health threat in tropical countries. The causative parasite of Malaria tropica, the severe form, is the protozoan Plasmodium falciparum. In humans, it infects red blood cells, compromising blood flow and tissue perfusion. This study aims to identify potential biomarkers and RNA networks in leukocyte transcriptomes from patients suffering from Malaria tropica. MATERIALS AND METHODS: We identified differentially regulated mRNAs and microRNAs in peripheral blood leukocytes of healthy donors and Malaria patients. Genes whose expression changes were not attributable to changes in leukocyte composition were used for bioinformatics analysis and network construction. Using a previously published cohort of community-acquired pneumonia (CAP) patients, we established discriminating transcriptomic features versus Malaria. We aimed to establish differences between the patient groups by principal component (PCA) and receiving operator characteristic (ROC) analyses and in silico cell type deconvolution. KEY FINDINGS: We found 870 genes that were significantly differentially expressed between healthy donors and Malaria patients. E2F1, BIRC5 and CCNB1 were identified to be primarily responsible for PCA separation of these two groups. We searched for biological function and found that cell cycle processes were strongly activated. By in silico cell type deconvolution, we attribute this to an expansion of γδ T cells. Additional discrimination between CAP and Malaria yielded 445 differentially expressed genes, among which immune proteasome transcripts PSMB8, PSMB9 and PSMB10 were significantly induced in Malaria. SIGNIFICANCE: We identified transcripts from patient leukocytes that differentiate between healthy, Malaria and CAP, and indicate a biological context with potential pathophysiological relevance.


Asunto(s)
Malaria/genética , Adulto , Biomarcadores/sangre , Biología Computacional , Femenino , Expresión Génica/genética , Perfilación de la Expresión Génica/métodos , Humanos , Malaria/parasitología , Masculino , MicroARNs/sangre , MicroARNs/genética , Persona de Mediana Edad , Plasmodium falciparum/genética , Plasmodium falciparum/patogenicidad , ARN Mensajero/sangre , ARN Mensajero/genética , Transcriptoma/genética
14.
Life Sci ; 270: 119144, 2021 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-33545201

RESUMEN

Activation of hepatic stellate cells (HSCs) is an important event during the progress of liver fibrosis. MicroRNA (miR)-15b and miR-16 have been found to be involved in activation of HSCs. However, the roles of miR-15b/16 in liver fibrosis remain unclear. The expression of miR-15b/16 was decreased in TGF-ß1-stimulated LX-2 cells. Overexpression of miR-15b/16 in LX-2 cells suppressed TGF-ß1-induced cell proliferation and the expression levels of tissue inhibitor of metalloproteinase type 1, collagen type I, and α-smooth muscle actin. The activation of Smad2/3 caused by TGF-ß1 was repressed by miR-15b/16 overexpression. The two miRNAs directly bound to the 3'-UTR of lysyl oxidase-like 1 (LOXL1) and suppressed the LOXL1 expression. Furthermore, knockdown of LOXL1 attenuated miR-15b/16 downregulation-induced cell proliferation, fibrogenic response and phosphorylation of Smad2/3. Collectively, miR-15b/16 exhibited anti-fibrotic activity through regulation of Smad2/3 pathway.


Asunto(s)
Aminoácido Oxidorreductasas/genética , MicroARNs/genética , Regiones no Traducidas 3'/genética , Aminoácido Oxidorreductasas/metabolismo , Línea Celular Tumoral , Proliferación Celular/genética , Colágeno Tipo I/metabolismo , Expresión Génica/genética , Regulación de la Expresión Génica/genética , Células Estrelladas Hepáticas/metabolismo , Humanos , Cirrosis Hepática/genética , Cirrosis Hepática/metabolismo , Cirrosis Hepática/patología , MicroARNs/metabolismo , Fosforilación , Transducción de Señal/efectos de los fármacos , Proteína Smad2/metabolismo , Proteína smad3/metabolismo , Factor de Crecimiento Transformador beta1/metabolismo
15.
Gene ; 777: 145468, 2021 Apr 20.
Artículo en Inglés | MEDLINE | ID: mdl-33539942

RESUMEN

The environment contains a large extent of chemical information, which could be detected as olfactory sense. Olfactory in vertebrates plays important roles on many aspects during life time, including localizing prey or food, avoiding predators, mating behavior and social communication. Considering the essential role of olfactory receptors in the specific recognition of diverse stimuli, understanding the evolutionary dynamics of olfactory receptors in teleost means a lot, especially in the allotetraploid common carp, who has undergone the fourth whole-genome duplication event. Here, we identified the whole set of olfactory receptor genes in representative teleosts and found a significant contraction in common carp when compared with other teleosts. Odorant receptor genes (OR) occupy the most among four groups of olfactory receptors, including 33 functional genes and 16 pseudogenes. Furthermore, 6 trace amine-associated receptor (TAAR) genes (including 1 pseudogene), 7 odorant-related-A receptor genes, and 10 olfactory C family receptor genes (including 3 pseudogenes) were identified in common carp. Phylogenetic and motif analysis were performed to illustrate the phylogenetic relationship and structural conservation of teleost olfactory receptors. Selection pressure analysis suggested that olfactory receptor groups in common carp were all under relaxed purifying-selection. Additionally, gene expression divergences for olfactory receptor genes were investigated during embryonic development stages of common carp. We aim to determine the abundance of common carp olfactory receptor genes, explore the evolutionary fate and expression dynamics, and provide some genomic clues for the evolution of polyploid olfactory after whole-genome duplication and for future studies of teleost olfactory.


Asunto(s)
Carpas/genética , Receptores Odorantes/genética , Animales , Carpas/metabolismo , Bases de Datos Genéticas , Evolución Molecular , Proteínas de Peces/genética , Duplicación de Gen/genética , Expresión Génica/genética , Perfilación de la Expresión Génica/métodos , Genoma/genética , Estudio de Asociación del Genoma Completo , Genómica/métodos , Familia de Multigenes/genética , Filogenia , Receptores Odorantes/metabolismo , Vertebrados/genética
17.
Cancer Sci ; 112(4): 1376-1382, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33615636

RESUMEN

Enhancer of zeste homolog 2 (EZH2) is the catalytic subunit of polycomb repressive complex 2 (PRC2). Dysregulation of EZH2 causes alteration of gene expression and functions, thereby promoting cancer development. The regulatory function of EZH2 varies across different tumor types. The canonical role of EZH2 is gene silencing through catalyzing the trimethylation of lysine 27 of histone H3 (H3K27me3) in a PRC2-dependent manner. Accumulating evidence indicates that EZH2 has an H3K27me3-independent function as a transcriptional coactivator and plays a critical role in cancer initiation, development, and progression. In this review, we summarize the regulation and function of EZH2 and focus on the current understanding of the noncanonical role of EZH2 in cancer.


Asunto(s)
Proteína Potenciadora del Homólogo Zeste 2/genética , Neoplasias/genética , Animales , Expresión Génica/genética , Silenciador del Gen/fisiología , Histonas/genética , Humanos , Complejo Represivo Polycomb 2/genética
18.
Methods Mol Biol ; 2224: 29-45, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33606204

RESUMEN

Reporter mice transgenically expressing the bacterial (E. coli) lacZ gene encoding ß-galactosidase (ß-gal, EC 3.2.1.23) are a versatile and extensively used tool to study gene expression and cell lineage patterns. Enzymatic activity of the ß-gal reporter can be effectively visualized at cellular resolution either histochemically using 5-bromo-4-chloro-3-indolyl-ß-D-galactopyranoside (X-gal) or by immunofluorescent detection using a ß-gal-specific antibody. Here, we summarize protocols for the localization of ß-gal expressing cells in whole embryos or organs as well as in histological tissue sections of lacZ reporter mice and discuss their limitations and common pitfalls.


Asunto(s)
Expresión Génica/genética , Genes Reporteros/genética , Operón Lac/genética , Animales , Linaje de la Célula/genética , Embrión de Mamíferos/metabolismo , Escherichia coli/genética , Galactósidos/genética , Indoles , Ratones , Coloración y Etiquetado/métodos
19.
Methods Mol Biol ; 2244: 301-342, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33555594

RESUMEN

microRNAs (miRNAs) are small noncoding RNAs that regulate gene expression at the posttranscriptional level by binding to sites within the 3' untranslated regions of messenger RNA (mRNA) transcripts. The discovery of this completely new mechanism of gene regulation necessitated the development of a variety of techniques to further characterize miRNAs, their expression, and function. In this chapter, we will discuss techniques currently used in the miRNA field to detect, express and inhibit miRNAs, as well as methods used to identify and validate their targets, specifically with respect to the miRNAs encoded by human cytomegalovirus.


Asunto(s)
Citomegalovirus/genética , Inmunoprecipitación/métodos , MicroARNs/análisis , Regiones no Traducidas 3'/genética , Northern Blotting/métodos , Expresión Génica/genética , Regulación Viral de la Expresión Génica/genética , Humanos , MicroARNs/genética , ARN Mensajero/genética
20.
Methods Mol Biol ; 2243: 339-354, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33606267

RESUMEN

MicroRNAs (miRNAs) regulate gene expression by binding to mRNAs. Consequently, they reduce target gene expression levels and expression variability, also known as "noise." Single-cell RNA sequencing (scRNA-seq) technology has been used to study miRNA and mRNA expression in single cells, and has demonstrated its strength in quantifying cell-to-cell variation. Here we describe how to investigate miRNA regulation using data with both mRNA and miRNA expression in single cell format. We show that miRNAs reduce the expression levels and also expression noise of target genes in single cells. Finally, we also discuss potential improvements in experimental design and computational analysis of scRNA-seq in order to reduce or partition the technical noise.


Asunto(s)
Regulación de la Expresión Génica/genética , Redes Reguladoras de Genes/genética , MicroARNs/genética , Expresión Génica/genética , Humanos , ARN Mensajero/genética , Análisis de Secuencia de ARN/métodos , Análisis de la Célula Individual/métodos
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