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1.
Medicine (Baltimore) ; 98(33): e16807, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31415393

RESUMO

BACKGROUND: Sepsis is a serious clinical condition with a poor prognosis, despite improvements in diagnosis and treatment.Therefore, novel biomarkers are necessary that can help with estimating prognosis and improving clinical outcomes of patients with sepsis. METHODS: The gene expression profiles GSE54514 and GSE63042 were downloaded from the GEO database. DEGs were screened by t test after logarithmization of raw data; then, the common DEGs between the 2 gene expression profiles were identified by up-regulation and down-regulation intersection. The DEGs were analyzed using bioinformatics, and a protein-protein interaction (PPI) survival network was constructed using STRING. Survival curves were constructed to explore the relationship between core genes and the prognosis of sepsis patients based on GSE54514 data. RESULTS: A total of 688 common DEGs were identified between survivors and non-survivors of sepsis, and 96 genes were involved in survival networks. The crucial genes Signal transducer and activator of transcription 5A (STAT5A), CCAAT/enhancer-binding protein beta (CEBPB), Myc proto-oncogene protein (MYC), and REL-associated protein (RELA) were identified and showed increased expression in sepsis survivors. These crucial genes had a positive correlation with patients' survival time according to the survival analysis. CONCLUSIONS: Our findings indicate that the genes STAT5A, CEBPB, MYC, and RELA may be important in predicting the prognosis of sepsis patients.


Assuntos
Proteína beta Intensificadora de Ligação a CCAAT/metabolismo , Proteínas Proto-Oncogênicas c-myc/metabolismo , Fator de Transcrição STAT5/metabolismo , Sepse/genética , Sepse/mortalidade , Fator de Transcrição RelA/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Idoso , Idoso de 80 Anos ou mais , Biologia Computacional , Bases de Dados Genéticas , Regulação para Baixo , Feminino , Marcadores Genéticos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Mapas de Interação de Proteínas , Fatores de Tempo , Transcriptoma , Regulação para Cima
2.
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
3.
BMC Plant Biol ; 19(1): 370, 2019 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-31438851

RESUMO

BACKGROUND: Accumulating evidences show that SPLs are crucial regulators of plant abiotic stress tolerance and the highly conserved module miR156/SPL appears to balance plant growth and stress responses. The halophyte Tamarix chinensis is highly resistant to salt tress. SPLs of T. chinensis (TcSPLs) and theirs roles in salt stress responses remain elusive. RESULTS: In this study, we conducted a systematic analysis of the TcSPLs gene family including 12 members belonging to 7 groups. The physicochemical properties and conserved motifs showed divergence among groups and similarity in each group. The microRNA response elements (MREs) are conserved in location and sequence, with the exception of first MRE within TcSPL5. The miR156-targeted SPLs are identified by dual-luciferase reporter assay of MRE-miR156 interaction. The digital expression gene profiles cluster suggested potential different functions of miR156-targeted SPLs vs non-targeted SPLs in response to salt stress. The expression patterns analysis of miR156-targeted SPLs with a reverse expression trend to TcmiR156 suggested 1 h (salt stress time) could be a critical time point of post-transcription regulation in salt stress responses. CONCLUSIONS: Our work demonstrated the post-transcription regulation of miR156-targeted TcSPLs and transcription regulation of non-targeted TcSPLs in salt stress responses, and would be helpful to expound the miR156/SPL-mediated molecular mechanisms underlying T. chinensis salt stress tolerance.


Assuntos
MicroRNAs/fisiologia , Proteínas de Plantas/fisiologia , RNA de Plantas/fisiologia , Estresse Salino/genética , Tamaricaceae/genética , Fatores de Transcrição/fisiologia , Motivos de Aminoácidos , Sequência Conservada , Genes de Plantas , Família Multigênica , Filogenia , Transcriptoma
4.
BMC Plant Biol ; 19(1): 369, 2019 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-31438855

RESUMO

BACKGROUND: Cucumis melo is a suitable study material for investigation of fruit ripening owing to its climacteric nature. Long non-coding RNAs have been linked to many important biological processes, such as fruit ripening, flowering time regulation, and abiotic stress responses in plants. However, knowledge of the regulatory roles of lncRNAs underlying the ripening process in C. melo are largely unknown. In this study the complete transcriptome of Cucumis melo L. cv. Hetao fruit at four developmental stages was sequenced and analyzed. The potential role of lncRNAs was predicted based on the function of differentially expressed target genes and correlated genes. RESULTS: In total, 3857 lncRNAs were assembled and annotated, of which 1601 were differentially expressed between developmental stages. The target genes of these lncRNAs and the regulatory relationship (cis- or trans-acting) were predicted. The target genes were enriched with GO terms for biological process, such as response to auxin stimulus and hormone biosynthetic process. Enriched KEGG pathways included plant hormone signal transduction and carotenoid biosynthesis. Co-expression network construction showed that LNC_002345 and LNC_000154, which were highly expressed, might co-regulate with mutiple genes associated with auxin signal transduction and acted in the same pathways. We identified lncRNAs (LNC_000987, LNC_000693, LNC_001323, LNC_003610, LNC_001263 and LNC_003380) that were correlated with fruit ripening and the climacteric, and may participate in the regulation of ethylene biosynthesis and metabolism and the ABA signaling pathway. A number of crucial transcription factors, such as ERFs, WRKY70, NAC56, and NAC72, may also play important roles in the regulation of fruit ripening in C. melo. CONCLUSIONS: Our results predict the regulatory functions of the lncRNAs during melon fruit development and ripening, and 142 highly expressed lncRNAs (average FPKM > 100) were identified. These lncRNAs participate in the regulation of auxin signal transduction, ethylene, sucrose biosynthesis and metabolism, the ABA signaling pathway, and transcription factors, thus regulating fruit development and ripening.


Assuntos
Cucumis melo/genética , Frutas/genética , RNA Longo não Codificante/fisiologia , RNA de Plantas/fisiologia , Mapeamento Cromossômico , Climatério , Cucumis melo/crescimento & desenvolvimento , Frutas/crescimento & desenvolvimento , Perfilação da Expressão Gênica , Genoma de Planta , Fenótipo , Reguladores de Crescimento de Planta/metabolismo , Análise de Sequência de RNA , Transdução de Sinais , Transcriptoma
5.
Pestic Biochem Physiol ; 159: 98-106, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31400791

RESUMO

The cotton aphid, Aphis gossypii Glover, is a destructive global crop pest. Control of A. gossypii has relied heavily on the application of chemical insecticides. The cotton aphid has developed resistance to numerous insecticides, including imidacloprid, which has been widely used to control cotton pests in China since the 1990s. Our objective was to investigate the potential role of UDP-glycosyltransferases (UGTs) in imidacloprid resistance based on transcriptomic and proteomic analyses of field-originated imidacloprid-resistant (IMI_R) and -susceptible (IMI_S) A. gossypii clones. The transcriptomic and proteomic analyses revealed that 12 out of 512 differentially expressed genes and three out of 510 differentially expressed proteins were predicted as UDP-glycosyltransferase (UGT). Based on quantitative real-time PCR analysis, nine UGT genes, UGT343A4, UGT344A15, UGT344A16, UGT344B4, UGT344C7, UGT344C9, UGT344N4, UGT 24541, and UGT7630, were up-regulated in the IMI_R clone compared to the IMI_S clone. Meanwhile, UGT344A16, UGT344B4, UGT344C7, and UGT344N4 were overexpressed at the protein level based on western blot analysis. Furthermore, knockdown of UGT344B4 or UGT344C7 using RNA interference (RNAi) significantly increased sensitivity to imidacloprid in the IMI_R clone. In conclusion, UGTs potentially contributed to imidacloprid resistance in A. gossypii originating from cotton-growing regions of China. These results provide insights into the way we study insecticide resistance in cotton aphids.


Assuntos
Afídeos/efeitos dos fármacos , Glucosiltransferases/metabolismo , Neonicotinoides/farmacologia , Nitrocompostos/farmacologia , Animais , Afídeos/genética , Afídeos/metabolismo , Glucosiltransferases/genética , Resistência a Inseticidas/genética , Proteômica , Transcriptoma/genética
6.
Rinsho Ketsueki ; 60(7): 818-823, 2019.
Artigo em Japonês | MEDLINE | ID: mdl-31391372

RESUMO

Myelodysplastic syndromes (MDS), a group of heterogeneous hematopoietic disorders, are characterized by multi-lineage dysplasia and ineffective hematopoiesis. Despite identifying multiple gene mutations in patients with MDS, their main clinical features are similar. To resolve the discrepancy between genotypes and phenotypes, we performed transcriptome and epigenome analyses to ascertain the shared underlying mediator (s) of MDS etiology and identified HIF1A signaling as a central pathobiological mediator of MDS. HIF1A is a critical regulator for several physiological pathways associated with stem-cell maintenance, angiogenesis, glucose-metabolism, and immune activation. We identified dysregulated HIF1A signature in human patients with MDS. Using mouse genetic models, we demonstrated that the dysregulation of HIF1A could generate the clinically relevant diversity of MDS phenotypes by functioning as a signaling funnel for MDS-driver mutations. The genetic disruption of HIF1A resolves MDS phenotypes. These findings suggest that HIF1A is an effective therapeutic target for a broad spectrum of patients with MDS.


Assuntos
Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Síndromes Mielodisplásicas/genética , Animais , Hematopoese , Humanos , Camundongos , Mutação , Transdução de Sinais , Transcriptoma
7.
BMC Plant Biol ; 19(1): 338, 2019 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-31375063

RESUMO

BACKGROUND: In native environments plants frequently experience simultaneous or sequential unfavourable abiotic and biotic stresses. The plant's response to combined stresses is usually not the sum of the individual responses. Here we investigated the impact of cold on plant defense against subsequent herbivory by a generalist and specialist insect. RESULTS: We determined transcriptional responses of Arabidopsis thaliana to low temperature stress (4 °C) and subsequent larval feeding damage by the lepidopteran herbivores Mamestra brassicae (generalist), Pieris brassicae (specialist) or artificial wounding. Furthermore, we compared the performance of larvae feeding upon cold-experienced or untreated plants. Prior experience of cold strongly affected the plant's transcriptional anti-herbivore and wounding response. Feeding by P. brassicae, M. brassicae and artificial wounding induced transcriptional changes of 1975, 1695, and 2239 genes, respectively. Of these, 125, 360, and 681 genes were differentially regulated when cold preceded the tissue damage. Overall, prior experience of cold mostly reduced the transcriptional response of genes to damage. The percentage of damage-responsive genes, which showed attenuated transcriptional regulation when cold preceded the tissue damage, was highest in M. brassicae damaged plants (98%), intermediate in artificially damaged plants (89%), and lowest in P. brassicae damaged plants (69%). Consistently, the generalist M. brassicae performed better on cold-treated than on untreated plants, whereas the performance of the specialist P. brassicae did not differ. CONCLUSIONS: The transcriptional defense response of Arabidopsis leaves to feeding by herbivorous insects and artificial wounding is attenuated by a prior exposure of the plant to cold. This attenuation correlates with improved performance of the generalist herbivore M. brassicae, but not the specialist P. brassicae, a herbivore of the same feeding guild.


Assuntos
Arabidopsis/fisiologia , Herbivoria , Animais , Arabidopsis/metabolismo , Borboletas/fisiologia , Resposta ao Choque Frio , Dieta , Regulação da Expressão Gênica de Plantas/fisiologia , Herbivoria/fisiologia , Larva , Mariposas/fisiologia , Folhas de Planta/metabolismo , Folhas de Planta/fisiologia , Transcriptoma
8.
Science ; 365(6455): 753-754, 2019 08 23.
Artigo em Inglês | MEDLINE | ID: mdl-31439782
9.
J Microbiol ; 57(9): 781-794, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31452043

RESUMO

The phytopathogenic Burkholderia species B. glumae and B. plantarii are the causal agents of bacterial wilt, grain rot, and seedling blight, which threaten the rice industry globally. Toxoflavin and tropolone are produced by these phytopathogens and are considered the most hostile biohazards with a broad spectrum of target organisms. However, despite their nonspecific toxicity, the effects of toxoflavin and tropolone on bacteria remain unknown. RNA-seq based transcriptome analysis was employed to determine the genome-wide expression patterns under phytotoxin treatment. Expression of 2327 and 830 genes was differentially changed by toxoflavin and tropolone, respectively. Enriched biological pathways reflected the down-regulation of oxidative phosphorylation and ribosome function, beginning with the inhibition of membrane biosynthesis and nitrogen metabolism under oxidative stress or iron starvation. Conversely, several systems such as bacterial chemotaxis, flagellar assembly, biofilm formation, and sulfur/taurine transporters were highly expressed as countermeasures against the phytotoxins. In addition, our findings revealed that three hub genes commonly induced by both phytotoxins function as the siderophore enterobactin, an iron-chelator. Our study provides new insights into the effects of phytotoxins on bacteria for better understanding of the interactions between phytopathogens and other microorganisms. These data will also be applied as a valuable source in subsequent applications against phytotoxins, the major virulence factor.


Assuntos
Antibacterianos/toxicidade , Burkholderia/química , Proteínas de Escherichia coli/genética , Escherichia coli/efeitos dos fármacos , Doenças das Plantas/microbiologia , Pirimidinonas/toxicidade , Triazinas/toxicidade , Tropolona/toxicidade , Antibacterianos/metabolismo , Burkholderia/metabolismo , Escherichia coli/genética , Escherichia coli/crescimento & desenvolvimento , Escherichia coli/metabolismo , Proteínas de Escherichia coli/metabolismo , Perfilação da Expressão Gênica , Regulação Bacteriana da Expressão Gênica/efeitos dos fármacos , Oryza/microbiologia , Pirimidinonas/metabolismo , Transcriptoma/efeitos dos fármacos , Triazinas/metabolismo , Tropolona/metabolismo
10.
Cancer Treat Rev ; 77: 57-66, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31279169

RESUMO

One of the major complications that patients experience during pharmacological treatment is the occurrence of adverse drug reactions (ADRs). The most affected organs are the liver, kidney, heart and the gastrointestinal-immune system. In comparison to the other organs, less progress has been made on human-relevant prediction of drug-induced intestinal toxicity, evidencing current large data gaps. The most widely used drugs that are associated with intestinal damage include chemotherapeutics, such as 5-Fluorouracil or Tyrosine Kinase Inhibitors (TKIs), as well as non-steroidal anti-inflammatory drugs (NSAIDs). Chemotherapeutics are regarded as inducers of acute intestinal toxicity whereas NSAIDs are associated with chronic inflammation of the intestine. In view of the fact that only a few studies have been dedicated to studying cellular and genomic responses in relation to drug-induced intestinal ADRs, little is known about how intestinal toxicity develops after exposure to such drugs or which molecular mechanisms are involved. Therefore, new models and experiments are required to establish transcriptomic responses and alterations of molecular markers induced by different medicines. This review summarizes the available information about transcriptomic responses and biomarkers of toxicity induced by 5-FU, NSAIDS or TKIs in different experimental models. Future investigation should address the challenges in predicting intestinal toxicity induced by drugs and unveil specific gene expression profiles that can be applied in the development of safer drugs.


Assuntos
Enteropatias/induzido quimicamente , Enteropatias/genética , Transcriptoma/efeitos dos fármacos , Anti-Inflamatórios não Esteroides/efeitos adversos , Fluoruracila/efeitos adversos , Humanos , Inibidores de Proteínas Quinases/efeitos adversos
11.
Medicine (Baltimore) ; 98(26): e15872, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31261495

RESUMO

Human epidermal growth factor receptor 2-positive (HER2+) breast cancer accounts for ∼20% of invasive breast cancers and is associated with poor prognostics. The recent outcome of HER2+ breast cancer treatment has been vastly improved owing to the application of antibody-targeted therapies. Trastuzumab (Herceptin) is a monoclonal antibody designed to target HER2+ breast cancer cells. In addition to improved survival in the adjuvant treatment of HER2+ breast cancer, trastuzumab treatment has also been associated with cardiotoxicity side effect. However, the molecular mechanisms of trastuzumab action and trastuzumab-mediated cardiotoxicity are still not fully understood. Previous research utilized bulk transcriptomics analysis to study the underlining mechanisms, which relied on averaging molecular signals from bulk tumor samples and might have overlooked key expression features within breast cancer tumor. In contrast to previous research, we compared the single cancer cell level transcriptome profile between trastuzumab-treated and nontreated patients to reveal a more in-depth transcriptome profile. A total of 461 significantly differential expressed genes were identified, including previously defined and novel gene expression signatures. In addition, we found that trastuzumab-enhanced MGP gene expression could be used as prognostics marker for longer patient survival in breast invasive carcinoma patients, and validated our finding using TCGA (The Cancer Genome Atlas) breast cancer dataset. Moreover, our study revealed a 48-gene expression signature that is associated with cell death of cardiomyocytes, which could be used as early biomarkers for trastuzumab-mediated cardiotoxicity. This work is the first study to look at single cell level transcriptome profile of trastuzumab-treated patients, providing a new understanding of the molecular mechanism(s) of trastuzumab action and trastuzumab-induced cardiotoxicity side effects.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Receptor ErbB-2/metabolismo , Transcriptoma/efeitos dos fármacos , Trastuzumab/uso terapêutico , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/epidemiologia , Proteínas de Ligação ao Cálcio/metabolismo , Carcinoma Ductal de Mama/tratamento farmacológico , Carcinoma Ductal de Mama/epidemiologia , Carcinoma Ductal de Mama/metabolismo , Proteínas da Matriz Extracelular/metabolismo , Feminino , Expressão Gênica/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Projetos Piloto , Prognóstico , RNA Mensageiro/metabolismo , Análise de Sequência de RNA , Análise de Célula Única , Análise de Sobrevida
12.
Medicine (Baltimore) ; 98(26): e16072, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31261517

RESUMO

Crohn disease (CD) is a multifactorial autoimmune disease which is characterized by chronic and recurrent gastrointestinal tract inflammatory disorder. However, the molecular mechanisms of CD remain unclear. Increasing evidences have demonstrated that circular RNAs (circRNAs) participate in the pathogenesis of a variety of disease and were considered as ideal biomarkers in human disease. This study aimed to investigate circRNA expression profiles and detect new biomarkers in inflammatory bowel disease (IBD). Differentially expression of circRNAs between CD and HCs (health controls) were screened by microarray analysis. Peripheral blood mononuclear cells (PBMCs) from 5 CD patients and 5 HCs were included in the microarray analysis. Then, the differences were validated by quantitative polymerase chain reaction (qPCR) following reverse transcription polymerase chain reaction (RT-PCR) in the patients of CD and sex- and age-matched HCs. The most differential expressed circRNA was further validated in ulcerative colitis (UC) patients. Statistical significance between CD, UC, and HCs was analyzed by Student t test for unpaired samples or one-way analysis of variance (ANOVA). Diagnostic value of each circRNA was assessed by receiver operating characteristic (ROC) curve. We identified 155 up-regulated circRNAs and 229 down-regulated ones by microarray analysis in PBMCs from CD patients compared with HCs. Besides, 4 circRNAs (092520, 102610, 004662, and 103124) were significantly up-regulated validated by RT-PCR and qPCR between CD and HCs. ROC curve analysis suggested important values of circRNAs (092520, 102610, 004662, and 103124) in CD diagnosis, with area under the curve (AUC) as 0.66, 0.78, 0.85, and 0.74, respectively. Then, we further identified that the relative expression levels of circRNA_004662 was upregulated significantly in CD patients compared with UC patients. Herein, the upregulation of the 4 circRNAs (092520, 102610, 004662, or 103124) in PBMCs can be served as potential diagnostic biomarkers of CD, and circRNA_004662 might be a novel candidate for differentiating CD from UC. Moreover, a circRNA-microRNA-mRNA network predicted that circRNA_004662 appeared to be correlated with mammalian target of rapamycin (mTOR) pathway.


Assuntos
Doença de Crohn/sangue , Leucócitos Mononucleares/metabolismo , RNA/sangue , Adolescente , Adulto , Idoso , Biomarcadores/sangue , Feminino , Humanos , Masculino , Análise em Microsséries , Pessoa de Meia-Idade , Curva ROC , Reação em Cadeia da Polimerase em Tempo Real , Transcriptoma , Adulto Jovem
13.
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
14.
J Cancer Res Clin Oncol ; 145(9): 2325-2333, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31317326

RESUMO

PURPOSE: Nodal positive lung adenocarcinoma includes wide range of survival. Several methods for the classification of nodal-positive lung cancer have been proposed. However, classification considering the impact of targetable genetic variants are lacking. The possibility of genetic variants for the better stratification of nodal positive lung adenocarcinoma was estimated. METHODS: Mutations of 36 genes between primary sites and metastatic lymph nodes (LNs) were compared using next-generation sequencing. Subsequently, mutations in EGFR and BRAF, rearrangements in ALK and ROS1 were evaluated in 69 resected pN1-2M0 adenocarcinoma cases. Recurrence-free survival (RFS), post-recurrence survival (PRS), and overall survival (OS) were evaluated with respect to targetable variants and tyrosine kinase inhibitor (TKI) therapy after recurrence. RESULTS: About 90% of variants were shared and allele frequencies were similar between primary and metastatic sites. In 69 pN1-2M0 cases, EGFR/ALK were positive in primary sites of 39 cases and same EGFR/ALK variants were confirmed in metastatic LNs of 96.7% tissue-available cases. Multivariate analyses indicated positive EGFR/ALK status was associated with worse RFS (HR 2.366; 95% CI 1.244-4.500; P = 0.009), and PRS was prolonged in cases receiving TKI therapy (no post-recurrence TKI therapies, HR 3.740; 95% CI 1.449-9.650; P = 0.006). OS did not differ with respect to targetable variants or TKI therapy. CONCLUSIONS: Cases harbouring targetable genetic variants had a higher risk of recurrence, but PRS was prolonged by TKI therapy. Classification according to the targetable genetic status provides a basis for predicting recurrence and determining treatment strategies after recurrence.


Assuntos
Adenocarcinoma de Pulmão/diagnóstico , Neoplasias Pulmonares/diagnóstico , Pulmão/metabolismo , Linfonodos/metabolismo , Mutação , Transcriptoma/genética , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/patologia , Idoso , Idoso de 80 Anos ou mais , Análise Mutacional de DNA/métodos , Feminino , Regulação Neoplásica da Expressão Gênica , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Pulmão/patologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Linfonodos/patologia , Metástase Linfática , Masculino , Análise em Microsséries/métodos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/genética , Prognóstico , Estudos Retrospectivos
15.
BMC Plant Biol ; 19(1): 321, 2019 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-31319815

RESUMO

BACKGROUND: Magnolia wufengensis is a new species of Magnolia L. and has considerable ornamental and economic value due to its unique characteristics. However, because of its characteristic of poor low temperature resistance, M. wufengensis is hardly popularization and application in the north of China. Furthermore, the mechanisms of gene regulation and signaling pathways involved in the cold-stress response remained unclear in this species. In order to solve the above-mentioned problems, we performed de novo transcriptome assembly and compared the gene expression under the natural (25 °C) and cold (4 °C) conditions for M. wufengensis seedlings. RESULTS: More than 46 million high-quality clean reads were produced from six samples (RNA was extracted from the leaves) and were used for performing de novo transcriptome assembly. A total of 59,764 non-redundant unigenes with an average length of 899 bp (N50 = 1,110) were generated. Among these unigenes, 31,038 unigenes exhibited significant sequence similarity to known genes, as determined by BLASTx searches (E-value ≤1.0E-05) against the Nr, SwissProt, String, GO, KEGG, and Cluster of COG databases. Based on a comparative transcriptome analysis, 3,910 unigenes were significantly differentially expressed (false discovery rate [FDR] < 0.05 and |log2FC (CT/CK)| ≥ 1) in the cold-treated samples, and 2,616 and 1,294 unigenes were up- and down-regulated by cold stress, respectively. Analysis of the expression patterns of 16 differentially expressed genes (DEGs) by quantitative real-time RT-PCR (qRT-PCR) confirmed the accuracy of the RNA-Seq results. Gene Ontology and KEGG pathway functional enrichment analyses allowed us to better understand these differentially expressed unigenes. The most significant transcriptomic changes observed under cold stress were related to plant hormone and signal transduction pathways, primary and secondary metabolism, and photosynthesis. In addition, 113 transcription factors, including members of the AP2-EREBP, bHLH, WRKY, MYB, NAC, HSF, and bZIP families, were identified as cold responsive. CONCLUSION: We generated a genome-wide transcript profile of M. wufengensis and a de novo-assembled transcriptome that can be used to analyze genes involved in biological processes. In this study, we provide the first report of transcriptome sequencing of cold-stressed M. wufengensis. Our findings provide important clues not only for understanding the molecular mechanisms of cold stress in plants but also for introducing cold hardiness into M. wufengensis.


Assuntos
Regulação da Expressão Gênica de Plantas/genética , Magnolia/genética , Resposta ao Choque Frio , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas/fisiologia , Genes de Plantas/genética , Genes de Plantas/fisiologia , Magnolia/fisiologia , Reação em Cadeia da Polimerase em Tempo Real , Análise de Sequência de DNA , Transdução de Sinais , Transcriptoma
16.
BMC Plant Biol ; 19(1): 329, 2019 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-31337346

RESUMO

BACKGROUND: Zinc finger proteins (ZFPs) containing only a single zinc finger domain play important roles in the regulation of plant growth and development, as well as in biotic and abiotic stress responses. To date, the evolutionary history and functions of the ZFP gene family have not been identified in cotton. RESULTS: In this paper, we identified 29 ZFP genes in Gossypium hirsutum. This gene family was divided into seven subfamilies, 22 of which were distributed over 17 chromosomes. Bioinformatic analysis revealed that 20 GhZFP genes originated from whole genome duplications and two originated from dispersed duplication events, indicating that whole genome duplication is the main force in the expansion of the GhZFP gene family. Most GhZFP8 subfamily genes, except for GhZFP8-3, were highly expressed during fiber cell growth, and were induced by brassinosteroids in vitro. Furthermore, we found that a large number of GhZFP genes contained gibberellic acid responsive elements, auxin responsive elements, and E-box elements in their promoter regions. Exogenous application of these hormones significantly stimulated the expression of these genes. CONCLUSIONS: Our findings reveal that GhZFP8 genes are involved in cotton fiber development and widely induced by auxin, gibberellin and BR, which provides a foundation for the identification of more downstream genes with potential roles in phytohormone stimuli, and a basis for breeding better cotton varieties in the future.


Assuntos
Gossypium/genética , Reguladores de Crescimento de Planta/fisiologia , Proteínas de Plantas/genética , Dedos de Zinco/genética , Brassinosteroides/metabolismo , Mapeamento Cromossômico , Sequência Conservada/genética , Giberelinas/fisiologia , Gossypium/fisiologia , Ácidos Indolacéticos/metabolismo , Filogenia , Proteínas de Plantas/fisiologia , Reação em Cadeia da Polimerase , Alinhamento de Sequência , Transcriptoma , Dedos de Zinco/fisiologia
17.
Cancer Immunol Immunother ; 68(8): 1303-1315, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31278476

RESUMO

Our previous work has demonstrated the high efficiency of CD8+ natural killer T (NKT)-like cells in killing antigen-bearing dendritic cells. To evaluate their role in the tumor microenvironment, we performed in vitro and in vivo antitumor experiments to investigate whether CD8+NKT-like cells could kill Yac-1 and B16 cells like NK cells and kill EL4-OVA8 cells in an antigen-specific manner like cytotoxic T lymphocytes (CTLs). Unlike NK1.1-CTLs, CD8+NKT-like cells also exhibit the capability to kill myeloid-derived suppressor cells (MDSCs) in an antigen-specific manner, indicative of their potential role in clearing tumor antigen-bearing MDSCs to improve the antitumor microenvironment. In vitro blocking experiments showed that granzyme B inhibitor efficiently suppressed the cytotoxicity of CD8+NKT-like cells against tumor cells and MDSCs, while Fas ligand (FasL) or tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) inhibition failed to produce similar effects. Transcriptomic and phenotypic analyses of CD8+NKT-like cells, NK cells, and NK1.1-CTLs indicated that CD8+NKT-like cells expressed both T-cell activation markers and NK cell markers, thus bearing features of both the activated T cells and NK cells. Taken together, CD8+NKT-like cells could exert NK- and CTL-like antitumor effects through the elimination of both tumor cells and MDSCs in a granzyme B-dependent manner.


Assuntos
Células Matadoras Naturais/imunologia , Células Supressoras Mieloides/imunologia , Células T Matadoras Naturais/imunologia , Neoplasias Experimentais/terapia , Linfócitos T Citotóxicos/imunologia , Animais , Antígenos CD8/metabolismo , Citotoxicidade Imunológica , Feminino , Granzimas/metabolismo , Humanos , Ativação Linfocitária , Melanoma Experimental , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Neoplasias Experimentais/imunologia , Transcriptoma , Microambiente Tumoral
18.
Parasit Vectors ; 12(1): 348, 2019 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-31300064

RESUMO

BACKGROUND: In the last decade, resistance to antimonials has become a serious problem due to the emergence of drug-resistant strains. Therefore, understanding the mechanisms used by Leishmania parasites to survive under drug pressure is essential, particularly for species of medical-veterinary importance such as L. amazonensis. METHODS: Here, we used RNA-seq technology to analyse transcriptome profiles and identify global changes in gene expression between antimony-resistant and -sensitive L. amazonensis promastigotes. RESULTS: A total of 723 differentially expressed genes were identified between resistant and sensitive lines. Comparative transcriptomic analysis revealed that genes encoding proteins involved in metabolism (fatty acids) and stress response, as well as those associated with antimony resistance in other Leishmania species, were upregulated in the antimony-resistant line. Most importantly, we observed upregulation of genes encoding autophagy proteins, suggesting that in the presence of trivalent stibogluconate (SbIII) L. amazonensis can activate these genes either as a survival strategy or to induce cell death, as has been observed in other parasites. CONCLUSIONS: This work identified global transcriptomic changes in an in vitro-adapted strain in response to SbIII. Our results provide relevant information to continue understanding the mechanism used by parasites of the subgenus Leishmania (L. amazonensis) to generate an antimony-resistant phenotype.


Assuntos
Gluconato de Antimônio e Sódio/farmacologia , Antiprotozoários/farmacologia , Resistência a Medicamentos/genética , Leishmania/efeitos dos fármacos , Leishmania/genética , Transcriptoma , DNA de Protozoário/genética , Perfilação da Expressão Gênica , Ontologia Genética , Fenótipo , Análise de Sequência de RNA , Regulação para Cima
19.
BMC Plant Biol ; 19(1): 289, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31262259

RESUMO

BACKGROUND: Banana anthracnose, caused by Colletotrichum musae, is one of the most severe postharvest diseases in banana. Melatonin is widely known for its role in enhancing plant stress tolerance. However, little is known about the control of melatonin on anthracnose in postharvest banana fruit. RESULTS: In this study, exogenous melatonin treatment could significantly reduce the incidence of anthracnose in ripe yellow banana fruit and delay fruit senescence. However, melatonin treatment did not affect the growth of Colletotrichum musae in vitro. Transcriptomic analysis of banana peel showed that 339 genes were up-regulated and 241 were down-regulated in the peel after melatonin treatment, compared with the control. Based on GO terms and KEGG pathway, these up-regulated genes were mainly categorized into signal transduction, cell wall formation, secondary metabolism, volatile compounds synthesis and response to stress, which might be related to the anti-anthracnose of banana fruit induced by melatonin treatment. This view was also supported by the increase of volatile compounds, cell wall components and IAA content in the melatonin-treated fruit peel via the metabolomic analysis. After melatonin treatment, auxin, ethylene and mitogen-activated protein kinase (MAPK) signaling pathways were enhanced, which might be involved in the enhanced fruit resistance by regulating physiological characteristics, disease-resistant proteins and metabolites. CONCLUSIONS: Our results provide a better understanding of the molecular processes in melatonin treatment delaying banana fruit senescence and anthracnose incidence.


Assuntos
Colletotrichum/fisiologia , Genes de Plantas , Melatonina/metabolismo , Metaboloma , Musa/microbiologia , Doenças das Plantas/microbiologia , Transcriptoma , Colletotrichum/efeitos dos fármacos , Frutas/microbiologia , Perfilação da Expressão Gênica , Melatonina/administração & dosagem , Metabolômica , Musa/genética
20.
BMC Plant Biol ; 19(1): 288, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31262271

RESUMO

BACKGROUND: Clubroot disease caused by Plasmodiophora brassicae (Phytomyxea, Rhizaria) is one of the economically most important diseases of Brassica crops. The formation of hypertrophied roots accompanied by altered metabolism and hormone homeostasis is typical for infected plants. Not all roots of infected plants show the same phenotypic changes. While some roots remain uninfected, others develop galls of diverse size. The aim of this study was to analyse and compare the intra-plant heterogeneity of P. brassicae root galls and symptomless roots of the same host plants (Brassica oleracea var. gongylodes) collected from a commercial field in Austria using transcriptome analyses. RESULTS: Transcriptomes were markedly different between symptomless roots and gall tissue. Symptomless roots showed transcriptomic traits previously described for resistant plants. Genes involved in host cell wall synthesis and reinforcement were up-regulated in symptomless roots indicating elevated tolerance against P. brassicae. By contrast, genes involved in cell wall degradation and modification processes like expansion were up-regulated in root galls. Hormone metabolism differed between symptomless roots and galls. Brassinosteroid-synthesis was down-regulated in root galls, whereas jasmonic acid synthesis was down-regulated in symptomless roots. Cytokinin metabolism and signalling were up-regulated in symptomless roots with the exception of one CKX6 homolog, which was strongly down-regulated. Salicylic acid (SA) mediated defence response was up-regulated in symptomless roots, compared with root gall tissue. This is probably caused by a secreted benzoic acid/salicylic acid methyl transferase from the pathogen (PbBSMT), which was one of the highest expressed pathogen genes in gall tissue. The PbBSMT derived Methyl-SA potentially leads to increased pathogen tolerance in uninfected roots. CONCLUSIONS: Infected and uninfected roots of clubroot infected plants showed transcriptomic differences similar to those previously described between clubroot resistant and susceptible hosts. The here described intra-plant heterogeneity suggests, that for a better understanding of clubroot disease targeted, spatial analyses of clubroot infected plants will be vital in understanding this economically important disease.


Assuntos
Brassica/genética , Doenças das Plantas/microbiologia , Plasmodioforídeos/fisiologia , Transcriptoma , Brassica/microbiologia , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Raízes de Plantas/microbiologia
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