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1.
Medicine (Baltimore) ; 99(1): e18445, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31895772

RESUMO

BACKGROUNDS: HER-2 positive breast cancer is a subtype of breast cancer with poor clinical outcome. The aim of this study was to identify differentially expressed genes (DEGs) for HER-2 positive breast cancer and elucidate the potential interactions among them. MATERIAL AND METHODS: Three gene expression profiles (GSE29431, GSE45827, and GSE65194) were derived from the Gene Expression Omnibus (GEO) database. GEO2R tool was applied to obtain DEGs between HER-2 positive breast cancer and normal breast tissues. Gene ontology (GO) annotation analysis and Kyoto Encyclopedia of Genes and Genome (KEGG) pathway enrichment analysis was performed by the Database for Annotation, Visualization and Integrated Discovery (David) online tool. Protein-protein interaction (PPI) network, hub gene identification and module analysis was conducted by Cytoscape software. Online Kaplan-Meier plotter survival analysis tool was also used to investigate the prognostic values of hub genes in HER-2 positive breast cancer patients. RESULTS: A total of 54 upregulated DEGs and 269 downregulated DEGs were identified. Among them, 10 hub genes including CCNB1, RAC1, TOP2A, KIF20A, RRM2, ASPM, NUSAP1, BIRC5, BUB1B, and CEP55 demonstrated by connectivity degree in the PPI network were screened out. In Kaplan-Meier plotter survival analysis, the overexpression of RAC1 and RRM2 were shown to be associated with an unfavorable prognosis in HER-2 positive breast cancer patients. CONCLUSIONS: This present study identified a number of potential target genes and pathways which might impact the oncogenesis and progression of HER-2 positive breast cancer. These findings could provide new insights into the detection of novel diagnostic and therapeutic biomarkers for this disease.


Assuntos
Neoplasias da Mama/genética , Regulação Neoplásica da Expressão Gênica/genética , Ribonucleosídeo Difosfato Redutase/genética , Proteínas rac1 de Ligação ao GTP/genética , Estudos de Casos e Controles , Biologia Computacional , Regulação para Baixo , Feminino , Humanos , Receptor ErbB-2 , Transcriptoma/genética , Regulação para Cima
2.
Chemosphere ; 238: 124571, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31472351

RESUMO

Rhodococcus exhibits strong adaptability to environmental stressors and plays a crucial role in environmental bioremediation. However, seasonal changes in ambient temperature, especially rapid temperature drops exert an adverse effect on in situ bioremediation. In this paper, we studied the cell morphology and fatty acid composition of an aniline-degrading strain Rhodococcus sp. CNS16 at temperatures of 30 °C, 20 °C, and 10 °C. At suboptimal temperatures, cell morphology of CNS16 changed from short rod-shaped to long rod or irregular shaped, and the proportion of unsaturated fatty acids was upregulated. Transcriptomic technologies were then utilized to gain detailed insights into the adaptive mechanisms of CNS16 subjected to suboptimal temperatures. The results showed that the number of gene responses was significantly higher at 10 °C than that at 20 °C. The inhibition of peptidoglycan synthase expression and up-regulation of Filamentous Temperature Sensitive as well as unsaturated fatty acid synthesis genes at suboptimal temperatures might be closely related to corresponding changes in cell morphology and fatty acids composition. Strain CNS16 showed loss of catalase and superoxide dismutase activity, and utilized thioredoxin-dependent thiol peroxidase to resist oxidative stress. The up-regulation of carotenoid and Vitamin B2 synthesis at 10 °C might also be involved in the resistance to oxidative stress. Amino acid metabolism, coenzyme and vitamin metabolism, ABC transport, and energy metabolism are essential for peptidoglycan synthesis and regulation of cellular metabolism; therefore, synergistically resisting environmental stress. This study provides a mechanistic basis for the regulation of aniline degradation in Rhodococcus sp. CNS16 at low temperatures.


Assuntos
Aclimatação/fisiologia , Compostos de Anilina/metabolismo , Ácidos Graxos/metabolismo , Peptidoglicano/biossíntese , Rhodococcus/metabolismo , Biodegradação Ambiental , Catalase/metabolismo , Temperatura Baixa , Estresse Oxidativo/fisiologia , Proteínas de Ligação às Penicilinas/biossíntese , Peroxirredoxinas/metabolismo , Rhodococcus/genética , Estações do Ano , Superóxido Dismutase/metabolismo , Transcriptoma
3.
Gene ; 728: 144288, 2020 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-31846710

RESUMO

Phytophthora root rot, caused by the soilborne oomycete pathogen Phytophthora capsici (Leon.), is a devastating disease causing significant losses in pepper production worldwide. To uncover the mechanism of root-mediated resistance to P. capsici we elucidated the dynamic transcriptome of whole pepper roots of the resistant accession CM334 and the susceptible accession NMCA10399 after P. capsici infection at 0, 12 and 36 hpi using RNA-Seq method. We detected that the roots of the resistant CM334 and the susceptible NMCA10399 had different transcriptional responses to P. capsici, suggesting the former activated a response to P. capsici earlier than the latter. KEGG enrichment analysis showed the pathways involved in the synthesis of secondary metabolites were those in which the most DEGs were enriched. Focusing on the gene regulation of phenylpropanoid biosynthesis-related genes, we found genes related to the key enzyme phenylalanine ammonia-lyase (PAL) were activated earlier with greater changes in the resistant accession than in the susceptible one. Moreover, genes related to cinnamoyl-CoA reductase (CCR1) were also upregulated in resistant roots but downregulated with great folder changes in susceptible roots. Briefly, we inferred that the phenylpropanoid biosynthesis pathway, especially cinnamaldehyde and lignin derived from its branches, played significant roles in pepper root resistance to P. capsici. These results provide new insight into root-mediated resistance to P. capsici in pepper.


Assuntos
Capsicum/genética , Resistência à Doença , Fenilpropionatos/metabolismo , Phytophthora/fisiologia , Doenças das Plantas/genética , Proteínas de Plantas/genética , Raízes de Plantas/genética , Transcriptoma , Capsicum/crescimento & desenvolvimento , Capsicum/microbiologia , Regulação da Expressão Gênica de Plantas , Fenilalanina Amônia-Liase/genética , Doenças das Plantas/microbiologia , Raízes de Plantas/crescimento & desenvolvimento , Raízes de Plantas/microbiologia
4.
J Urol ; 203(1): 62-72, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31112107

RESUMO

PURPOSE: Studies indicate that molecular subtypes in muscle invasive bladder cancer predict the clinical outcome. We evaluated whether subtyping by a simplified method and established classifications could predict the clinical outcome. MATERIALS AND METHODS: We subtyped institutional cohort 1 of 52 patients, including 39 with muscle invasive bladder cancer, an Oncomine™ data set of 151 with muscle invasive bladder cancer and TCGA (The Cancer Genome Atlas) data set of 402 with muscle invasive bladder cancer. Subtyping was done using simplified panels (MCG-1 and MCG-Ext) which included only transcripts common in published studies and were analyzed for predicting metastasis, and cancer specific, overall and recurrence-free survival. TCGA data set was further analyzed using the Lund taxonomy, the Bladder Cancer Molecular Taxonomy Group Consensus and TCGA 2017 mRNA subtype classifications. RESULTS: Muscle invasive bladder cancer specimens from cohort 1 and the Oncomine data set showed intratumor heterogeneity for transcript and protein expression. MCG-1 subtypes did not predict the outcome on univariate or Kaplan-Meier analysis. On multivariate analysis N stage (p ≤0.007), T stage (p ≤0.04), M stage (p=0.007) and/or patient age (p=0.01) predicted metastasis, cancer specific and overall survival, and/or the cisplatin based adjuvant chemotherapy response. In TCGA data set publications showed that subtypes risk stratified patients for overall survival. Consistently the MCG-1 and MCG-Ext subtypes were associated with overall but not recurrence-free survival on univariate and Kaplan-Meier analyses. TCGA data set included 21 low grade specimens of the total of 402 and subtypes associated with tumor grade (p=0.005). However, less than 1% of muscle invasive bladder cancer cases are low grade. In only high grade specimens the MCG-1 and MCG-Ext subtypes could not predict overall survival. On univariate analysis subtypes according to the Bladder Cancer Molecular Taxonomy Group Consensus, TCGA 2017 and the Lund taxonomy were associated with tumor grade (p <0.0001) and overall survival (p=0.01 to <0.0001). Regardless of classification, subtypes had about 50% to 60% sensitivity and specificity to predict overall and recurrence-free survival. On multivariate analyses N stage and lymphovascular invasion consistently predicted recurrence-free and overall survival (p=0.039 and 0.003, respectively). CONCLUSIONS: Molecular subtypes reflect bladder tumor heterogeneity and are associated with tumor grade. In multiple cohorts and subtyping classifications the clinical parameters outperformed subtypes for predicting the outcome.


Assuntos
Biomarcadores Tumorais/análise , Carcinoma de Células de Transição/genética , Carcinoma de Células de Transição/patologia , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/patologia , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Gradação de Tumores , Invasividade Neoplásica , Metástase Neoplásica , Estadiamento de Neoplasias , Fenótipo , Valor Preditivo dos Testes , Prognóstico , Medição de Risco , Fatores de Risco , Transcriptoma
5.
Gene ; 725: 144159, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-31629818

RESUMO

Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related deaths worldwide due to its frequent metastasis, tumor recurrence, and lack of curative treatment. However, the underlying molecular mechanisms involved in HCC progression remain unclear. Here, we analyzed the global gene expression of spontaneous liver tumor tissue from CBA/CaJ mice by RNA-Seq and identified 10,706 and 10,374 genes in the normal and liver tumor groups, respectively. Only 9793 genes were expressed in both, 913 genes were identified in only the liver tumor group, and 581 genes were found in normal liver tissues. There were 2054 differentially expressed genes (DEGs), with 975 down-regulated genes and 1079 up-regulated genes. Gene ontology (GO) term enrichment analysis showed that 43 up-regulated genes were significantly associated with cell cycle regulation and hundreds of up-regulated genes were related to cell migration, adhesion, or metabolic processes. KEGG pathway enrichment also demonstrated that some DEGs were tightly associated with the cell cycle, extracellular matrix (ECM)-receptor interactions, as well as protein digestion and absorption pathways, indicating that the activation of these oncogenic cascades was closely related to tumor liver progression in CBA/CaJ mice. Ninety-three genes with elevated expression levels preferentially localized in microtubules, kinetochores, and spindles play an important role during mitosis and meiosis and are associated with the reorganization of the cytoskeleton in cancer cells during migration and invasion. Some ECM-related genes were significantly different in the tumor group, including collagen types I, III, IV, V, and VI, non-collagenous glycoproteins, laminin, and fibronectin. We further validated the functions of upregulated genes, such as cyclin-dependent kinase 1 (CDK1) and polo-like kinase 1 (PLK1), with regards to cell cycle regulation, apoptosis, and proliferation in normal human liver or liver tumor-derived cell lines. Our results indicated that the cell cycle dysregulation, ECM-receptor interaction, and cytoskeleton-associated genes in mouse livers may promote HCC progression and deciphering the function of the genes will help investigators understand the underlying molecular mechanism of HCC.


Assuntos
Neoplasias Hepáticas Experimentais/genética , Animais , Apoptose/genética , Proteína Quinase CDC2/metabolismo , Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Linhagem Celular Tumoral , Perfilação da Expressão Gênica/métodos , Regulação Neoplásica da Expressão Gênica , Ontologia Genética , Redes Reguladoras de Genes , Neoplasias Hepáticas Experimentais/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos CBA , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Transdução de Sinais , Transcrição Genética , Transcriptoma
6.
Gene ; 725: 144160, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-31639431

RESUMO

Bambusapervariabilis × Dendrocalamopsisgrandis, a fast-growing and easily propagated bamboo species, has been extensively planted in the southern China, resulting in huge ecological benefits. In recent years, it was found that the pathogenic fungus Arthrinium phaeospermum caused the death of a large amount of bamboo. In this study, the transcriptome of B. pervariabilis × D. grandis, induced by inactivated protein AP-toxin from A. phaeospermum was sequenced and analyzed, to reveal the resistance mechanism induced by biotic agents of B. pervariabilis × D. grandis against A. phaeospermum at the gene level. Transcriptome sequencing was performed by Illumina HiSeq 2000 in order to analyze the differentially expressed genes (DEGs) of B. pervariabilis × D. grandis in response to different treatment conditions. In total, 201,875,606 clean reads were obtained, and the percentage of Q30 bases in each sample was more than 94.21%. There were 6398 DEGs in the D-J group (inoculation with a pathogenic spore suspension after three days of AP-toxin induction) compared to the S-J group (inoculation with a pathogenic spore suspension after inoculation of sterile water for three days) with 3297 up-regulated and 3101 down-regulated genes. For the D-S group (inoculation with sterile water after inoculation of AP-toxin for three days), there were 2032 DEGs in comparison to the S-S group (inoculation with sterile water only), with 1035 up-regulated genes and 997 down-regulated genes. These identified genes were mainly involved in lignin and phytoprotein synthesis, tetrapyrrole synthesis, redox reactions, photosynthesis, and other processes. The fluorescence quantitative results showed that 22 pairs of primer amplification products were up-regulated and 7 were down-regulated. The rate of similarity between these results and the sequencing results of the transcription group was 100%, which confirmed the authenticity of the transcriptome sequencing results. Redox proteins, phenylalanine ammonia lyase, and S-adenosine-L-methionine synthetase, among others, were highly expressed; these results may indicate the level of disease resistance of the bamboo. These results provide a foundation for the further exploration of resistance genes and their functions.


Assuntos
Bambusa/genética , Sasa/genética , Xylariales/genética , China , Resistência à Doença , Fungos/patogenicidade , Perfilação da Expressão Gênica/métodos , Regulação da Expressão Gênica de Plantas/genética , Micoses/genética , Proteínas de Plantas/genética , Toxinas Biológicas , Transcriptoma , Xylariales/metabolismo
7.
Gene ; 725: 144170, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-31647996

RESUMO

Caragana korshinskii Kom. is a legume shrub that is widely distributed across desert habitats with gravely, sandy, and saline soils in Asia and Africa. C. korshinskii has highly developed roots and a strong tolerance to abiotic stress. At present, there are few genetic studies of C. korshinskii because of the limited availability of genomic resources. To understand the comprehensive mechanisms that are associated with drought tolerance, we used RNA-seq to survey the differentially expressed genes (DEGs) in comparisons of drought-treated and control plants. After analysing the sequencing results, we found 440 differentially expressed genes existing in drought-treated and control plants. Among the DEGs, 39 unigenes showed up-regulated expression after drought treatment, while 401 unigenes were down-regulated. We used the KEGG database to annotate these drought-induced genes; 126 unigenes were identified by KEGG pathway annotation, and approximately 28% of the unigenes with known function fell into categories related to fatty acid metabolism, starch, sucrose metabolism, and nitrogen metabolism, suggesting that these pathways or processes may be involved in the drought response. Finally, we confirmed that one gene has a potential function in drought tolerance. Our study is the first to provide transcriptomic resources for Caragana korshinskii and to determine its digital gene expression profile under conditions of drought stress using the assembled transcriptomic data for reference. These data provide a valuable resource for genetic and genomic studies of desert plants under abiotic stress conditions.


Assuntos
Caragana/genética , Perfilação da Expressão Gênica/métodos , Estresse Fisiológico/genética , Secas , Fabaceae/genética , Regulação da Expressão Gênica de Plantas/genética , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Anotação de Sequência Molecular , RNA/genética , Transcriptoma/genética
8.
Gut ; 69(1): 177-186, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-30954949

RESUMO

OBJECTIVE: Increased de novo fatty acid (FA) synthesis and cholesterol biosynthesis have been independently described in many tumour types, including hepatocellular carcinoma (HCC). DESIGN: We investigated the functional contribution of fatty acid synthase (Fasn)-mediated de novo FA synthesis in a murine HCC model induced by loss of Pten and overexpression of c-Met (sgPten/c-Met) using liver-specific Fasn knockout mice. Expression arrays and lipidomic analysis were performed to characterise the global gene expression and lipid profiles, respectively, of sgPten/c-Met HCC from wild-type and Fasn knockout mice. Human HCC cell lines were used for in vitro studies. RESULTS: Ablation of Fasn significantly delayed sgPten/c-Met-driven hepatocarcinogenesis in mice. However, eventually, HCC emerged in Fasn knockout mice. Comparative genomic and lipidomic analyses revealed the upregulation of genes involved in cholesterol biosynthesis, as well as decreased triglyceride levels and increased cholesterol esters, in HCC from these mice. Mechanistically, loss of Fasn promoted nuclear localisation and activation of sterol regulatory element binding protein 2 (Srebp2), which triggered cholesterogenesis. Blocking cholesterol synthesis via the dominant negative form of Srebp2 (dnSrebp2) completely prevented sgPten/c-Met-driven hepatocarcinogenesis in Fasn knockout mice. Similarly, silencing of FASN resulted in increased SREBP2 activation and hydroxy-3-methyl-glutaryl-CoA (HMG-CoA) reductase (HMGCR) expression in human HCC cell lines. Concomitant inhibition of FASN-mediated FA synthesis and HMGCR-driven cholesterol production was highly detrimental for HCC cell growth in culture. CONCLUSION: Our study uncovers a novel functional crosstalk between aberrant lipogenesis and cholesterol biosynthesis pathways in hepatocarcinogenesis, whose concomitant inhibition might represent a therapeutic option for HCC.


Assuntos
Carcinoma Hepatocelular/metabolismo , Colesterol/biossíntese , Ácido Graxo Sintase Tipo I/metabolismo , Ácidos Graxos/biossíntese , Neoplasias Hepáticas/metabolismo , Animais , Vias Biossintéticas/efeitos dos fármacos , Vias Biossintéticas/genética , Carcinogênese/genética , Carcinoma Hepatocelular/genética , Linhagem Celular Tumoral , Ácido Graxo Sintase Tipo I/genética , Feminino , Técnicas de Silenciamento de Genes , Inativação Gênica , Genômica , Humanos , Hidroximetilglutaril-CoA Redutases/genética , Hidroximetilglutaril-CoA Redutases/metabolismo , Neoplasias Hepáticas/genética , Masculino , Camundongos , Camundongos Knockout , PTEN Fosfo-Hidrolase/metabolismo , Proteínas Proto-Oncogênicas c-met/metabolismo , Proteína de Ligação a Elemento Regulador de Esterol 2/genética , Proteína de Ligação a Elemento Regulador de Esterol 2/metabolismo , Transcriptoma
9.
J Clin Pathol ; 73(1): 17-22, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31300530

RESUMO

OBJECTIVE: Cutaneous squamous cell carcinoma (cSCC) is the second most common malignancy, most frequently affecting the head and neck. Treatment often requires surgery and can have significant functional morbidity. Research into disease pathogenesis and second line medical management of cSCC is limited. We assess genetic mutations in high-risk, primary head and neck cutaneous squamous cell carcinomas (HNcSCC) that may hinder or be beneficial for use of targeted therapy in disease management. METHODS: Genetic alterations and variant allele frequencies (VAFs) were analysed using a clinically relevant 48 gene panel in 10 primary high-risk non-metastatic treatment-naïve HNcSCC to evaluate applicability of targeted therapeutics. Variants present at all VAFs were evaluated for pathogenicity. Somatic mutation patterns of individual tumours were analysed. RESULTS: High-risk HNcSCC showed a high proportion (82%) of C to T transitions in keeping with ultraviolet-mediated damage. There was significant intratumour genetic heterogeneity in this cohort (MATH scores 20-89) with the two patients <45 years of age showing highest intratumour heterogeneity. TP53 was altered at VAF >22% in all cases, and mutations with highest VAF were observed in tumour suppressor genes in 80%. 70% of cases demonstrated at least one mutation associated with treatment resistance (KIT S821F, KIT T670I, RAS mutations at codons 12 and 13). CONCLUSION: We demonstrate high proportion tumour suppressor loss of function mutations, high intratumour genetic heterogeneity, and presence of well recognised resistance mutations in treatment naïve primary HNcSCC. These factors pose challenges for successful utilisation of targeted therapies.


Assuntos
Biomarcadores Tumorais/genética , Heterogeneidade Genética , Neoplasias de Cabeça e Pescoço/genética , Mutação , Neoplasias Cutâneas/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Tomada de Decisão Clínica , Resistencia a Medicamentos Antineoplásicos/genética , Feminino , Predisposição Genética para Doença , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Terapia de Alvo Molecular , Seleção de Pacientes , Fenótipo , Medicina de Precisão , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Transcriptoma
10.
J Clin Pathol ; 73(1): 23-29, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31422372

RESUMO

AIMS: The histological distinction of intrahepatic cholangiocarcinoma (ICC) from metastatic adenocarcinoma remains a challenge. The primary goal was to evaluate the diagnostic value of morphology and albumin expression in the diagnosis of ICC. METHODS: We evaluated morphological patterns in 120 ICCs and 677 non-hepatic adenocarcinomas and performed in situ hybridisation (ISH) stain for albumin in the former cohort (retrospective cohort). We also identified 119 samples from primary and metastatic lesions, the validation cohort, in which albumin ISH was performed as part of the diagnostic workup. Targeted sequencing was performed on selected cases. We also mined existing expression profiling data including cases from The Cancer Genome Atlas (TCGA) (41 760 unique samples). RESULTS: In the retrospective cohort, 45% of ICCs and <1% of non-hepatic adenocarcinomas showed a cholangiolar pattern; albumin ISH was positive in 93% of ICCs with significant intratumorous heterogeneity. In the validation cohort, 29% of ICCs showed a cholangiolar pattern and 88% expressed albumin, while all metastatic non-hepatic neoplasms were negative (n=37) (sensitivity 88% and specificity 100%). Targetable genetic alterations (IDH mutations and FGFR2 fusions) were identified in 31% of ICCs (10 of 32). An analysis of the TCGA data validated the specificity of the albumin assay. CONCLUSIONS: The cholangiolar pattern and albumin RNA ISH distinguishes ICC from metastatic adenocarcinoma with high specificity. Given the high prevalence of targetable mutations in ICC, albumin RNA ISH is an essential component in the workup of tumours of uncertain origin. A specific diagnosis of ICC could trigger molecular testing and uncover targetable genetic alterations.


Assuntos
Albuminas/genética , Neoplasias dos Ductos Biliares/genética , Neoplasias dos Ductos Biliares/patologia , Biomarcadores Tumorais/genética , Colangiocarcinoma/genética , Colangiocarcinoma/patologia , Hibridização In Situ , Adenocarcinoma/genética , Adenocarcinoma/secundário , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias dos Ductos Biliares/secundário , Biópsia por Agulha , Diagnóstico Diferencial , Feminino , Perfilação da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Retrospectivos , Transcriptoma , Adulto Jovem
11.
J Clin Pathol ; 73(1): 51-56, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31662438

RESUMO

Fibroepithelial tumours are biphasic neoplasms of the breast comprising the common benign fibroadenomas and the less common phyllodes tumours (PTs), which have recurrent potential. PTs are classified into benign, borderline or malignant, based on five histopathological criteria, with malignant PTs having the highest metastatic capability. Accurate diagnosis can be challenging due to the subjective assessment of histopathological parameters. Fibroadenomas bear morphological similarities to benign PTs, while borderline and malignant PTs can sometimes be difficult to distinguish from other spindle cell tumours of the breast. From clonality studies to whole-genome sequencing, much research has been conducted to elucidate the molecular pathogenesis of fibroepithelial tumours, which, in turn, have allowed leveraging the findings for diagnostic applications, including grading of PTs. The most noteworthy discovery was of recurrent MED12 mutations in both fibroadenomas and PTs. Subsequent studies also uncovered relatively frequent genetic mutations in TERT promoter and RARA A customised panel of 16 most frequently mutated genes in fibroepithelial tissues has been compiled previously and has contributed to resolving a few diagnostic dilemmas. This review will introduce the 16 genes and focus on the top three that are most frequently mutated in fibroepithelial tumours: MED12, TERT, and RARA.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias da Mama/genética , Complexo Mediador/genética , Mutação , Neoplasias Fibroepiteliais/genética , Receptor alfa de Ácido Retinoico/genética , Telomerase/genética , Neoplasias da Mama/patologia , Feminino , Predisposição Genética para Doença , Humanos , Taxa de Mutação , Neoplasias Fibroepiteliais/patologia , Fenótipo , Fatores de Risco , Transcriptoma
12.
Food Chem ; 306: 125629, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-31629298

RESUMO

To understand the mechanism of the color formation of pepper fruit, integrative analysis of the metabolome and transcriptome profiles was performed in pepper varieties with 4 different fruit colors. A total of 188 flavonoids were identified, and most of the anthocyanins, flavonols and flavones showed markedly higher abundances in purple variety than in other varieties, which was linked to the high expression of flavonoid synthesis and regulatory genes. Using weighted gene co-expression network analyses, modules related to flavonoid synthesis and candidate genes that regulate flavonoid synthesis and transport were identified. Furthermore, the analysis of 12 carotenoids showed that the content of xanthophylls at 50 days after anthesis was significantly different between the four pepper varieties, which was resulted from the differential expressions of genes downstream of the carotenoid pathway. Our results provide new insights into the understanding of the synthesis and accumulation of flavonoids and carotenoids in pepper fruit.


Assuntos
Capsicum/metabolismo , Capsicum/química , Carotenoides/metabolismo , Cor , Flavonoides/metabolismo , Metaboloma , Transcriptoma , Verduras/química , Verduras/metabolismo
14.
Equine Vet J ; 52(1): 98-103, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30991461

RESUMO

BACKGROUND: Salmonella enterica subsp. enterica serovar Abortusequi (S. Abortusequi) is a serotype restricted to equines, which produces abortion outbreaks. Nowadays the disease is being reported in different countries including Argentina thus generating an important impact in the equine industry. Molecular characterization of the 95 kb virulence plasmid and the spvC gene of S. Abortusequi demonstrated their importance in the pathogenicity of the serotype. In the last decades, high clonality of S. Abortusequi was identified in Japan, Mongolia and Croatia. OBJECTIVES: The aim of this work was to characterize S. Abortusequi isolates obtained in Argentina between 2011 and 2016 by virulence-gene profiling and pulsed-field gel electrophoresis. STUDY DESIGN: Case report. METHODS: S. Abortusequi isolates were studied by virulence-gene profiling and pulsed-field gel electrophoresis. RESULTS: Four virulence profiles and nine pulsed-field gel electrophoresis pulsotypes were identified among the 27 isolates included in the study. Different strains were found in the same outbreak and/or farm suggesting the presence of different sources of infection or mutation of isolates. MAIN LIMITATIONS: The number of related and nonrelated strains. More isolates may be necessary for a more intensive study. CONCLUSIONS: Most strains presented the same virulence profile, being positive for all the studied genes except gipA and sopE1, which are involved in intestinal virulence. Only few isolates showed different results in the same outbreak or farm. Unlike other studies, our results demonstrate a considerable diversity of S. Abortusequi pulsed-field gel electrophoresis pulsotypes, which suggests that different sources of infection may be involved within the same outbreak.


Assuntos
Genótipo , Doenças dos Cavalos/microbiologia , Salmonelose Animal/microbiologia , Salmonella enterica/genética , Animais , Argentina/epidemiologia , Doenças dos Cavalos/epidemiologia , Cavalos , Salmonelose Animal/epidemiologia , Salmonella enterica/classificação , Salmonella enterica/patogenicidade , Transcriptoma , Virulência
15.
Chemosphere ; 239: 124747, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31514003

RESUMO

BACKGROUNDS: Polychlorinated biphenyls are persistent environmental pollutants associated with the onset of non-alcoholic fatty liver disease in humans, but there is limited information on the underlying mechanism. In the present study, we investigated the alterations in gene expression profiles in normal human liver cells L-02 following exposure to 2, 3, 3', 4, 4', 5 - hexachlorobiphenyl (PCB 156), a potent compound that may induce non-alcoholic fatty liver disease. METHODS: The L-02 cells were exposed to PCB 156 for 72 h and the contents of intracellular triacylglyceride and total cholesterol were subsequently measured. Microarray analysis of mRNAs and long non-coding RNAs (lncRNAs) in the cells was also performed after 3.4 µM PCB 156 treatment. RESULTS: Exposure to PCB 156 (3.4 µM, 72 h) resulted in significant increases of triacylglyceride and total cholesterol concentrations in L-02 cells. Microarray analysis identified 222 differentially expressed mRNAs and 628 differentially expressed lncRNAs. Gene Ontology and pathway analyses associated the differentially expressed mRNAs with metabolic and inflammatory processes. Moreover, lncRNA-mRNA co-expression network revealed 36 network pairs comprising 10 differentially expressed mRNAs and 34 dysregulated lncRNAs. The results of bioinformatics analysis further indicated that dysregulated lncRNA NONHSAT174696, lncRNA NONHSAT179219, and lncRNA NONHSAT161887, as the regulators of EDAR, CYP1B1, and ALDH3A1 respectively, played an important role in the PCB 156-induced lipid metabolism disorder. CONCLUSION: Our findings provide an overview of differentially expressed mRNAs and lncRNAs in L-02 cells exposed to PCB 156, and contribute to the field of polychlorinated biphenyl-induced non-alcoholic fatty liver disease.


Assuntos
Fígado/efeitos dos fármacos , Bifenilos Policlorados/toxicidade , Transcriptoma/efeitos dos fármacos , Aldeído Desidrogenase/genética , Linhagem Celular , Colesterol/metabolismo , Citocromo P-450 CYP1B1/genética , Receptor Edar/genética , Perfilação da Expressão Gênica , Humanos , Fígado/citologia , Fígado/fisiologia , Hepatopatia Gordurosa não Alcoólica/induzido quimicamente , Hepatopatia Gordurosa não Alcoólica/patologia , Análise de Sequência com Séries de Oligonucleotídeos , RNA Longo não Codificante , RNA Mensageiro/metabolismo , Testes de Toxicidade , Triglicerídeos/metabolismo
16.
Chemosphere ; 238: 124661, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31472350

RESUMO

Toxicities of the marine algae Alexandrium minutum and its excreted gonyautoxins (GTXs) to the marine crustacean Artemia salina were investigated. Mortality was observed for neither larvae nor adult A. salina exposed to A. minutum at a density of 5000 cells/mL or 0.5 µM GTX2/3. After exposure, the full transcriptome of adult A. salina was assembled and functionally annotated. A total of 599,286 transcripts were obtained, which were clustered into 515,196 unigenes. Results of the transcriptional effect level index revealed that direct exposure to the toxic algae A. minutum caused greater alterations in the transcriptome than did exposure to the extracellular product GTX2/3. Mechanisms of effects were different between exposure of A. salina to A. minutum cells or GTX2/3. Exposure to A. minutum modulated formation of the ribonucleoprotein complex and metabolism of amino acids and lipids in A. salina. Exposure to GTX2/3 exposure inhibited expression of genes related to metabolism of chitin, which might result in disruption of molting process or disturbed sheath morphogenesis. Overall, effects on transcription observed in this study represent the first report based on application of next generation sequencing techniques to investigate the transcriptomic response of A. salina exposed to an environmentally realistic level of A. minutum or GTX2/3.


Assuntos
Artemia/genética , Saxitoxina/análogos & derivados , Transcriptoma/efeitos dos fármacos , Animais , Artemia/fisiologia , Quitina/genética , Quitina/metabolismo , Dinoflagelados/citologia , Dinoflagelados/metabolismo , Sequenciamento de Nucleotídeos em Larga Escala , Saxitoxina/farmacologia , Saxitoxina/toxicidade
17.
Zhongguo Zhong Yao Za Zhi ; 44(22): 4820-4829, 2019 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-31872588

RESUMO

Agkistrodon acutus is a traditional Chinese herb medicine which has immunological regulation,anti-tumor,anti-inflammatory and analgesic effects,which is mainly used for the treatment of rheumatoid arthritis,ankylosing spondylitis,sjogren's syndrome and tumors. In order to excavate more important functional genes from A. acutus,the transcriptome of the venom gland was sequenced by the Illumina Hi Seq 4000,and 32 862 unigenes were assembled. Among them,26 589 unigenes were mapped to least one public database. 2 695 unigenes were annotated and assigned to 62 TF families,and 5 920 SSR loci were identified. The majority of mapped unigenes was from Protobothrops mucrosquamatus in the NR database,which revealed their closest homology. Three secretory phospholipase A_2 with different amino acid sequences showed similar spatial structures and all had well-conserved active sites. The 3 D structural models of C-type lectin showed conserved glycosylation binding sites( Asn45). This study will lay the foundation for the further study of the function of snake venom protein,and promoting the development and utilization of genome resources from A. acutus.


Assuntos
Agkistrodon/genética , Venenos de Crotalídeos , Venenos de Serpentes/genética , Animais , Perfilação da Expressão Gênica , Serpentes , Transcriptoma
18.
BMC Bioinformatics ; 20(Suppl 24): 596, 2019 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-31861975

RESUMO

BACKGROUND: Adenosine-to-inosine RNA editing can markedly diversify the transcriptome, leading to a variety of critical molecular and biological processes in mammals. Over the past several years, researchers have developed several new pipelines and software packages to identify RNA editing sites with a focus on downstream statistical analysis and functional interpretation. RESULTS: Here, we developed a user-friendly public webserver named MIRIA that integrates statistics and visualization techniques to facilitate the comprehensive analysis of RNA editing sites data identified by the pipelines and software packages. MIRIA is unique in that provides several analytical functions, including RNA editing type statistics, genomic feature annotations, editing level statistics, genome-wide distribution of RNA editing sites, tissue-specific analysis and conservation analysis. We collected high-throughput RNA sequencing (RNA-seq) data from eight tissues across seven species as the experimental data for MIRIA and constructed an example result page. CONCLUSION: MIRIA provides both visualization and analysis of mammal RNA editing data for experimental biologists who are interested in revealing the functions of RNA editing sites. MIRIA is freely available at https://mammal.deepomics.org.


Assuntos
Mamíferos , Edição de RNA , Análise de Sequência de RNA , Transcriptoma , Animais , Genoma , Genômica , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Mamíferos/genética , RNA/genética , Análise de Sequência de RNA/métodos
19.
Zhongguo Zhong Yao Za Zhi ; 44(21): 4605-4611, 2019 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-31872654

RESUMO

To analysis the SSR loci information in the transcriptome of Cordyceps sinensis and develop SSR molecular markers,MISA(MicroSatellite) software was used to analyze the microsatellites information from 16 875 unigene sequences and SSR primer designed by Primer 3. 0. In total,5 899 SSRs were detected in 4 252 unigene with the distribution frequency of 34. 99%,which was represented by 74 repeat motifs and SSR loci occurred per 7 952 bp in length. In the SSRs,the mono-nucleotide was the most abundant repeat motif(42. 5%),followed by tri-nucleotide(34. 48%),C/G and CCG/CGG were the dominant repeat motifs,respectively. The number of repetitions of the six SSR repeat types was concentrated on 5 to 12 times,and the length was mostly less than 24 bp. A total of 12 282 pairs of primers were screened and selected 20 pairs of primers for validity detection randomly,10 pairs of primers amplified the expected specific bands,and primer P1 has significant polymorphism. Moreover,it was found that unigene containing SSR loci is mainly related to genetic and environmental functions after GO and KEGG annotation. In conclusion,these SSR loci in the transcriptome of O. sinensis are high in frequency,rich in primitive types,high in polymorphism,and highly available,which will provides abundant candidate molecular markers for its genetic diversity analysis,resource identification protection,and gene function research.


Assuntos
Cordyceps/genética , Transcriptoma , Etiquetas de Sequências Expressas , Repetições de Microssatélites , Polimorfismo Genético
20.
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi ; 36(6): 1038-1042, 2019 Dec 25.
Artigo em Chinês | MEDLINE | ID: mdl-31875380

RESUMO

Circular RNA (circRNA) is a type of single-stranded RNA that binds in a closed loop structure by covalent bond. It is highly expressed and has diverse functions in the eukaryotic transcriptome, and it also has the potential to regulate the process of cell differentiation. Stem cells are important seed cells and common research tools in the field of tissue engineering, which have multi-directional differentiation potential and low immunogenicity. Its clinical application for the treatment of diseases has broad prospects, and the research on their differentiation mechanism has gradually penetrated to the molecular level. A number of studies have shown that circRNA participates in stem cell differentiation and plays a key role through a variety of pathways. This article focuses on the expression changes of circRNA during stem cell differentiation and its research advancement in regulating the differentiation mechanism of various stem cells. The review also prospects its possible role in tissue regeneration and repair, in order to further study the molecular mechanism of circRNA involved in stem cell differentiation and provide ideas for clinical practice of stem cells in biomedical engineering.


Assuntos
Diferenciação Celular , Engenharia Tecidual , RNA , Células-Tronco , Transcriptoma
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