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The study aimed to identify common differentially expressed lncRNAs from manually curated ulcerative colitis (UC) gene expression omnibus (GEO) datasets. Nine UC transcriptomic datasets of clearly annotated human colonic biopsies were included in the study. The datasets were manually curated to select active UC samples and controls. R packages geneknitR, gprofiler, clusterProfiler were used for gene symbol annotation. The R EdgeR package was used to analyze differential expression. This resulted in a total of nineteen lncRNAs that were differentially expressed in at least three datasets of the nine GEO datasets. Several of the differentially expressed lncRNAs found in UC were associated with promoting colorectal cancer (CRC) through regulating gene expression, epithelial to mesenchymal transition (EMT), cell cycle progression, and by promoting tumor proliferation, invasion, and migration. The expression of several lncRNAs varied between disease states and tissue locations within the same disease state. The identified differentially expressed lncRNAs may function as general markers for active UC independent of biopsy location, age, gender, or treatment, thereby representing a comparative resource for future comparisons using available GEO UC datasets.
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DNA methylation has been implied to play a role in the immune dysfunction associated with inflammatory bowel disease (IBD) and the disease development of ulcerative colitis (UC). Changes of the DNA methylation and correlated gene expression in patient samples with inactive UC might reveal possible regulatory features important for further treatment options for UC. Targeted bisulfite sequencing and whole transcriptome sequencing were performed on mucosal biopsies from patients with active UC (UC, n = 14), inactive UC (RM, n = 20), and non-IBD patients which served as controls (NN, n = 11). The differentially methylated regions (DMRs) were identified by DMRseq. Correlation analysis was performed between DMRs and their nearest differentially expressed genes (DEGs). Principal component analysis (PCA) was performed based on correlated DMR regulated genes. DMR regulated genes then were functional annotated. Cell-type deconvolutions were performed based on methylation levels. The comparisons revealed a total of 38 methylation-regulated genes in inactive UC that are potentially regulated by DMRs (correlation p value < 0.1). Several methylation-regulated genes could be identified in inactive UC participating in IL-10 and cytokine signalling pathways such as IL1B and STAT3. DNA methylation events in inactive UC seem to be fine-tuned by the balancing pro- and anti- inflammatory pathways to maintain a prevailed healing process to restore dynamic epithelium homeostasis.
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Colite Ulcerativa , Doenças Inflamatórias Intestinais , Humanos , Colite Ulcerativa/patologia , Metilação de DNA , Biópsia , Doenças Inflamatórias Intestinais/genética , Anti-InflamatóriosRESUMO
Long non-coding RNAs (lncRNAs) have been shown to play a role in the pathogenesis of ulcerative colitis (UC). Although epigenetic processes such as DNA methylation and lncRNA expression are well studied in UC, the importance of the interplay between the two processes has not yet been fully explored. It is, therefore, believed that interactions between environmental factors and epigenetics contribute to disease development. Mucosal biopsies from 11 treatment-naïve UC patients and 13 normal controls were used in this study. From each individual sample, both whole-genome bisulfite sequencing data (WGBS) and lncRNA expression data were analyzed. Correlation analysis between lncRNA expression and upstream differentially methylated regions (DMRs) was used to identify lncRNAs that might be regulated by DMRs. Furthermore, proximal protein-coding genes associated with DMR-regulated lncRNAs were identified by correlating their expression. The study identified UC-associated lncRNAs such as MIR4435-2HG, ZFAS1, IL6-AS1, and Pvt1, which may be regulated by DMRs. Several genes that are involved in inflammatory immune responses were found downstream of DMR-regulated lncRNAs, including SERPINB1, CCL18, and SLC15A4. The interplay between lncRNA expression regulated by DNA methylation in UC might improve our understanding of UC pathogenesis.
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Colite Ulcerativa , RNA Longo não Codificante , Serpinas , Humanos , Colite Ulcerativa/genética , RNA Longo não Codificante/genética , Metilação de DNA , Epigênese Genética , Processamento de Proteína Pós-Traducional , Serpinas/genéticaRESUMO
Due to the lack of clinical, immunologic, genetic, and laboratory markers to predict remission in ulcerative colitis (UC) without relapse, there is no clear recommendation regarding withdrawal of therapy. Therefore, this study was to investigate if transcriptional analysis together with Cox survival analysis might be able to reveal molecular markers that are specific for remission duration and outcome. Mucosal biopsies from patients in remission with active treatment-naïve UC and healthy control subjects underwent whole-transcriptome RNA-seq. Principal component analysis (PCA) and Cox proportional hazards regression analysis were applied to the remission data concerning duration and status of patients. A randomly chosen remission sample set was used for validation of the applied methods and results. The analyses distinguished two different UC remission patient groups with respect to remission duration and outcome (relapse). Both groups showed that altered states of UC with quiescent microscopic disease activity are still present. The patient group with the longest remission duration and no relapse revealed specific and increased expression of antiapoptotic factors belonging to the MTRNR2-like gene family and non-coding RNAs. In summary, the expression of anti-apoptotic factors and non-coding RNAs may contribute to personalized medicine approaches in UC by improving patient stratification for different treatment regimens.
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Colite Ulcerativa , Humanos , Colite Ulcerativa/diagnóstico , Colite Ulcerativa/genética , Colite Ulcerativa/tratamento farmacológico , BiomarcadoresRESUMO
Here we explored the role of interleukin-1ß (IL-1ß) repressor cytokine, IL-1 receptor antagonist (IL-1rn), in both healthy and abnormal hematopoiesis. Low IL-1RN is frequent in acute myeloid leukemia (AML) patients and represents a prognostic marker of reduced survival. Treatments with IL-1RN and the IL-1ß monoclonal antibody canakinumab reduce the expansion of leukemic cells, including CD34+ progenitors, in AML xenografts. In vivo deletion of IL-1rn induces hematopoietic stem cell (HSC) differentiation into the myeloid lineage and hampers B cell development via transcriptional activation of myeloid differentiation pathways dependent on NFκB. Low IL-1rn is present in an experimental model of pre-leukemic myelopoiesis, and IL-1rn deletion promotes myeloproliferation, which relies on the bone marrow hematopoietic and stromal compartments. Conversely, IL-1rn protects against pre-leukemic myelopoiesis. Our data reveal that HSC differentiation is controlled by balanced IL-1ß/IL-1rn levels under steady-state, and that loss of repression of IL-1ß signaling may underlie pre-leukemic lesion and AML progression.
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Leucemia Mieloide Aguda , Receptores de Interleucina-1 , Humanos , Receptores de Interleucina-1/genética , Medula Óssea , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/genética , Proliferação de Células , Antígenos CD34RESUMO
BACKGROUND: In ulcerative colitis (UC), the molecular mechanisms that drive disease development and patient response to therapy are not well understood. A significant proportion of patients with UC fail to respond adequately to biologic therapy. Therefore, there is an unmet need for biomarkers that can predict patients' responsiveness to the available UC therapies as well as ascertain the most effective individualised therapy. Our study focused on identifying predictive signalling pathways that predict anti-integrin therapy response in patients with UC. METHODS: We retrieved and pre-processed two publicly accessible gene expression datasets (GSE73661 and GSE72819) of UC patients treated with anti-integrin therapies: (1) 12 non-IBD controls and 41 UC patients treated with Vedolizumab therapy, and (2) 70 samples with 58 non-responder and 12 responder UC patient samples treated with Etrolizumab therapy without non-IBD controls. We used a diffusion-based signalling model which is mainly focused on the T-cell receptor signalling network. The diffusion model uses network connectivity between receptors and transcription factors. RESULTS: The network diffusion scores were able to separate VDZ responder and non-responder patients before treatment better than the original gene expression. On both anti-integrin treatment datasets, the diffusion model demonstrated high predictive performance for discriminating responders from non-responders in comparison with 'nnet'. We have found 48 receptor-TF pairs identified as the best predictors for VDZ therapy response with AUC ≥ 0.76. Among these receptor-TF predictors pairs, FFAR2-NRF1, FFAR2-RELB, FFAR2-EGR1, and FFAR2-NFKB1 are the top best predictors. For Etrolizumab, we have identified 40 best receptor-TF pairs and CD40-NFKB2 as the best predictor receptor-TF pair (AUC = 0.72). We also identified subnetworks that highlight the network interactions, connecting receptors and transcription factors involved in cytokine and fatty acid signalling. The findings suggest that anti-integrin therapy responses in cytokine and fatty acid signalling can stratify UC patient subgroups. CONCLUSIONS: We identified signalling pathways that may predict the efficacy of anti-integrin therapy in UC patients and personalised therapy alternatives. Our results may lead to the advancement of a promising clinical decision-making tool for the stratification of UC patients.
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Colite Ulcerativa , Anticorpos Monoclonais Humanizados , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Citocinas , Ácidos Graxos/uso terapêutico , Fármacos Gastrointestinais/uso terapêutico , Humanos , Fatores de Transcrição/uso terapêutico , Resultado do TratamentoRESUMO
BACKGROUND AND AIMS: The study aimed to identify yet unknown and uncharacterized long non-coding RNAs (lncRNAs) in treatment-naïve ulcerative colitis (UC), and to define their possible roles in UC pathogenesis. For that purpose, accurate quantification methods for lncRNA transcript detection, multiple and "stringent" strategies were applied. New insights in the regulation of functional genes and pathways of relevance for UC through expression of lncRNAs are expected. METHODS: The study was based on sequencing data derived from a data set consisting of treatment-naïve UC patients (n = 14) and control subjects (n = 16). Two complementary aligners were used to identify lncRNAs. Several different steps were used to validate differential expression including plotting the reads over the annotation for manual inspection. To help determine potential lncRNA involvement in biological processes, KEGG pathway enrichment was done on protein-coding genes which co-expressed with the lncRNAs. RESULTS: A total of 99 lncRNAs were identified in UC. The lncRNAs which were not previously characterized (n = 15) in UC or other autoimmune diseases were selected for down-stream analysis. In total, 602 protein-coding genes correlated with the uncharacterized lncRNAs. KEGG pathway enrichment analysis revealed involvement of lncRNAs in two significantly enriched pathways, lipid and atherosclerosis, and T-cell receptor signaling. CONCLUSION: This study identified a set of 15 yet uncharacterized lncRNAs which may be of importance for UC pathogenesis. These lncRNAs may serve as potential diagnostic biomarkers and might be of use for the development of UC treatment strategies in the future.
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Severe ulcerative colitis (UC) is a potentially life-threatening disease with a potential colorectal cancer (CRC) risk. The aim of this study was to explore the relationship between transcriptomic and genome-wide DNA methylation profiles in a well-stratified, treatment-naïve severe UC patient population in order to define specific epigenetic changes that could be responsible for the grade of disease severity. Mucosal biopsies from treatment-naïve severe UC patients (n = 8), treatment-naïve mild UC (n = 8), and healthy controls (n = 8) underwent both whole transcriptome RNA-Seq and genome-wide DNA bisulfite- sequencing, and principal component analysis (PCA), cell deconvolutions and diverse statistical methods were applied to obtain a dataset of significantly differentially expressed genes (DEGs) with correlation to DNA methylation for severe UC. DNA hypo-methylation correlated with approximately 80% of all DEGs in severe UC when compared to mild UC. Enriched pathways of annotated hypo-methylated genes revealed neutrophil degranulation, and immuno-regulatory interactions of the lymphoid system. Specifically, hypo-methylated anti-inflammatory genes found for severe UC were IL10, SIGLEC5, CD86, CLMP and members of inflammasomes NLRP3 and NLRC4. Hypo-methylation of anti-inflammatory genes during severe UC implies an interplay between the epithelium and lamina propria in order to mitigate inflammation in the gut. The specifically DNA hypo-methylated genes found for severe UC can potentially be useful biomarkers for determining disease severity and in the development of new targeted treatment strategies for severe UC patients.
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Colite Ulcerativa/metabolismo , DNA/metabolismo , Adulto , Idoso , Biomarcadores/metabolismo , Metilação de DNA , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Adulto JovemRESUMO
Motivation: Resistance to anti-TNF therapy in subgroups of ulcerative colitis (UC) patients is a major challenge and incurs significant treatment costs. Identification of patients at risk of nonresponse to anti-TNF is of major clinical importance. To date, no quantitative computational framework exists to develop a complex biomarker for the prognosis of UC treatment. Modelling patient-wise receptor to transcription factor (TF) network connectivity may enable personalized treatment. Results: We present an approach for quantitative diffusion analysis between receptors and TFs using gene expression data. Key TFs were identified using pandaR. Network connectivities between immune-specific receptor-TF pairs were quantified using network diffusion in UC patients and controls. The patient-specific network could be considered a complex biomarker that separates anti-TNF treatment-resistant and responder patients both in the gene expression dataset used for model development and separate independent test datasets. The model was further validated in rheumatoid arthritis where it successfully discriminated resistant and responder patients to tocilizumab treatment. Our model may contribute to prognostic biomarkers that may identify treatment-resistant and responder subpopulations of UC patients. Availability and implementation: Software is available at https://github.com/Amy3100/receptor2tfDiffusion. Supplementary information: Supplementary data are available at Bioinformatics Advances online.
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BACKGROUND: This study addresses whether existing specific transcriptional profiles can improve and support the current status of the definition of ulcerative colitis (UC) remission apart from the existing endoscopic, histologic, and laboratory scoring systems. For that purpose, a well-stratified UC patient population in remission was compared to active UC and control patients and was investigated by applying the next-generation technology RNA-Seq. METHODS: Mucosal biopsies from patients in remission (n = 14), patients with active UC (n = 14), and healthy control patientss (n = 16) underwent whole-transcriptome RNA-Seq. Principal component analysis, cell deconvolution methods, gene profile enrichment, and pathway enrichment methods were applied to define a specific transcriptional signature of UC in remission. RESULTS: Analyses revealed specific transcriptional signatures for UC in remission with increased expression of genes involved in O-glycosylation (MUC17, MUC3A, MUC5AC, MUC12, SPON1, B3GNT3), ephrin-mediated repulsion of cells (EFNB2E, EFNA3, EPHA10, EPHA1), GAP junction trafficking (TUBA1C, TUBA4A, TUBB4B, GJB3, CLTB), and decreased expression of several toll-like receptors (TLR1, TLR3, TLR5, TLR6). CONCLUSIONS: This study reveals specific transcriptional signatures for remission. Partial restoration and improvement of homeostasis in the epithelial mucus layer and revival of immunological functions were observed. A clear role for bacterial gut flora composition can be implied. The results can be useful for the development of treatment strategies for UC in remission and may be useful targets for further investigations aiming to predict the outcome of UC in the future.
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Colite Ulcerativa/genética , Colo/metabolismo , Mucosa Intestinal/metabolismo , Transcriptoma/genética , Adulto , Estudos de Casos e Controles , Conexinas/metabolismo , Efrinas/metabolismo , Feminino , Glicosilação , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Pessoa de Meia-Idade , Mucinas/metabolismo , Análise de Componente Principal , Indução de Remissão , Receptores Toll-Like/metabolismoRESUMO
BACKGROUND AND AIMS: The aim of this study was to investigate the genome-wide DNA methylation status in treatment-naïve ulcerative colitis [UC], and to explore the relationship between DNA methylation patterns and gene expression levels in tissue biopsies from a well-stratified treatment-naïve UC patient group. METHODS: Mucosal biopsies from treatment-naïve patients [n = 10], and a healthy control group [n = 11] underwent genome-wide DNA bisulfite sequencing. Principal component analysis [PCA] and diverse statistical methods were applied to obtain a dataset of differentially methylated genes. DNA methylation annotation was investigated using the UCSC Genome Browser. Gene set enrichments were obtained using the Kyoto Encyclopaedia of Genes and Genomes [KEGG] and PANTHER. RESULTS: Of all significantly differentially expressed genes [DEGs], 25% correlated with DNA methylation patterns; 30% of these genes were methylated at CpG sites near their transcription start site [TSS]. Hyper-methylation was observed for genes involved in homeostasis and defence, whereas hypo-methylation was observed for genes playing a role in immune response [i.e. chemokines and interleukins]. Of the differentially DNA methylated genes, 25 were identified as inflammatory bowel disease [IBD] susceptibility genes. Four genes [DEFFA6, REG1B, BTNL3, OLFM4] showed DNA methylation in the absence of known CpG islands. CONCLUSIONS: Genome-wide DNA methylation analysis revealed distinctive functional patterns for hyper-and hypo-methylation in treatment-naïve UC. These distinct patterns could be of importance in the development and pathogenesis of UC. Further investigation of DNA methylation patterns may be useful in the development of the targeting of epigenetic processes, and may allow new treatment and target strategies for UC patients.
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Colite Ulcerativa/genética , Metilação de DNA , Expressão Gênica , Mucosa Intestinal/metabolismo , Fator de Necrose Tumoral alfa/genética , Adulto , Idoso , Biópsia , Estudos de Casos e Controles , Quimiocinas/genética , Colite Ulcerativa/patologia , Ilhas de CpG/genética , Feminino , Predisposição Genética para Doença/genética , Homeostase/genética , Humanos , Interleucinas/genética , Mucosa Intestinal/patologia , Masculino , Pessoa de Meia-Idade , RNA Mensageiro/metabolismo , Análise de Sequência de DNARESUMO
BACKGROUND AND AIMS: Ulcerative colitis [UC] is a chronic inflammatory disease that effects the gastrointestinal tract and is considered one of the most prominent and common forms of inflammatory bowel disease [IBD]. This study aimed to define and describe the entire transcriptomic landscape in a well-stratified, treatment-naïve UC patient population compared with control patients by using next-generation technology, RNA-Seq. METHODS: Mucosal biopsies from treatment-naïve UC patients [n = 14], and healthy controls [n = 16] underwent RNA-Seq. Principal component analysis [PCA], cell deconvolution methods, and diverse statistical methods were applied to obtain and characterise a dataset of significantly differentially expressed genes [DEGs]. RESULTS: Analyses revealed 1480 significantly DEGs in treatment-naïve UC when compared with controls. Cell populations of monocytes, T cells, neutrophils, B cells/ lymphoid cells, and myeloid cells were increased during inflammation, whereas the fraction of epithelial cells were reduced in UC, which is reflected by the DEGs; 79 DEGs were identified as IBD susceptibility genes, and 58 DEGs were expressed in a gender-specific manner. MUC5B, REG3A, DEFA5, and IL33 might be considered as colorectal cancer [CRC] risk factors following UC in males. AQP9 together with CLDN2 may have a role regulating tissue-specific physiological properties in tight junctions in UC. An additional functional role for AQP9 in the synthesis and/or the function of mucus can be implied. CONCLUSIONS: This study reveals new potential players in UC pathogenesis in general, and provides evidence for a gender-dependent pathogenesis for UC. These results can be useful for the development of personalised treatment strategies for UC in the future.
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Colite Ulcerativa/genética , Colite Ulcerativa/patologia , Neoplasias Colorretais/genética , Transcriptoma , Adulto , Idoso , Aquaporinas/genética , Biópsia , Estudos de Casos e Controles , Claudinas/genética , Colite Ulcerativa/sangue , Colo Sigmoide/patologia , Feminino , Perfilação da Expressão Gênica , Predisposição Genética para Doença/genética , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Interleucina-33/genética , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Mucina-5B/genética , Proteínas Associadas a Pancreatite/genética , Análise de Sequência de RNA , Fatores Sexuais , Junções Íntimas/genética , Adulto Jovem , alfa-Defensinas/genéticaRESUMO
UNLABELLED: Despite anti-dsDNA antibodies constitute a wide range of specificities, they are considered as the hallmark for systemic lupus erythematosus (SLE). OBJECTIVE: To identify clinical phenotypes associated with anti-dsDNA antibodies, independently of any clinical diagnoses. METHODS: Patients with recent onset of any rheumatic symptoms were screened for antinuclear antibodies (ANA). All ANA-positive and matching ANA-negative patients were examined, and their clinical phenotypes were registered, using a systematic chart formulated after consensus between the participating centres. All patients were tested for different anti-dsDNA antibody specificities with assays habitually used in each participating laboratory. Crithidia Luciliae Immuno Fluorescence Test (CLIFT) was performed three times (with two different commercial kits); solid and solution phase ELISA were performed four times. Associations between clinical phenotypes and results of anti-dsDNA assays were evaluated by linear regression analysis (LRA) and principal component analysis (PCA). RESULTS: Totally, 292 ANA-positive and 292 matching ANA-negative patients were included in the study. A full dataset for statistical analysis was obtained in 547 patients. Anti-dsDNA antibodies were most frequently detected by ELISA. LRA showed that overall positivity of anti-dsDNA antibodies was associated with proteinuria and pleuritis. Alopecia was significantly associated only with CLIFT-positivity. Besides confirming the same findings, PCA showed that combined positivity of CLIFT and ELISA was also associated with lymphopenia. CONCLUSIONS: Our results show that different anti-dsDNA antibody specificities are associated with nephropathy, pleuritis, alopecia and lymphopenia, regardless of the diagnosis. It may challenge the importance of anti-dsDNA antibodies as a diagnostic hallmark for SLE.
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BACKGROUND: Angiogenesis is regarded as a hallmark in cancer development, and anti-angiogenic treatment is presently used in non-small cell lung cancer (NSCLC) patients. MicroRNAs (miRs) are small non-coding, endogenous, single stranded RNAs that regulate gene expression. In this study we aimed to identify significantly altered miRs related to angiogenesis in NSCLC. METHODS: From a large cohort of 335 NSCLC patients, paraffin-embedded samples from 10 patients with a short disease specific survival (DSS), 10 with a long DSS and 10 normal controls were analyzed. The miRs were quantified by microarray hybridization and selected miRs were validated by real-time qPCR. The impacts of different pathways, including angiogenesis, were evaluated by Gene Set Enrichment Analysis (GSEA) derived from Protein ANalysis THrough Evolutionary Relationship (PANTHER). One of the most interesting candidate markers, miR-155, was validated by in situ hybridization (ISH) in the total cohort (nâ=â335) and correlation analyses with several well-known angiogenic markers were done. RESULTS: 128 miRs were significantly up- or down-regulated; normal versus long DSS (nâ=â68) and/or normal versus short DSS (nâ=â63) and/or long versus short DSS (nâ=â37). The pathway analysis indicates angiogenesis-related miRs to be involved in NSCLC. There were strong significant correlations between the array hybridization and qPCR validation data. The significantly altered angiogenesis-related miRs of high interest were miR-21, miR-106a, miR-126, miR-155, miR-182, miR-210 and miR-424. miR-155 correlated significantly with fibroblast growth factor 2 (FGF2) in the total cohort (râ=â0.17, Pâ=â0.002), though most prominent in the subgroup with nodal metastasis (râ=â0.34, P<0.001). CONCLUSIONS: Several angiogenesis-related miRs are significantly altered in NSCLC. Further studies to understand their biological functions and explore their clinical relevance are warranted.
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Carcinoma Pulmonar de Células não Pequenas/irrigação sanguínea , Carcinoma Pulmonar de Células não Pequenas/genética , Neoplasias Pulmonares/irrigação sanguínea , Neoplasias Pulmonares/genética , MicroRNAs/genética , Neovascularização Patológica/genética , Transcriptoma , Idoso , Biomarcadores Tumorais/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Estudos de Coortes , Feminino , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Reprodutibilidade dos TestesRESUMO
BACKGROUND: Spot 42 was discovered in Escherichia coli nearly 40 years ago as an abundant, small and unstable RNA. Its biological role has remained obscure until recently, and is today implicated in having broader roles in the central and secondary metabolism. Spot 42 is encoded by the spf gene. The gene is ubiquitous in the Vibrionaceae family of gamma-proteobacteria. One member of this family, Aliivibrio salmonicida, causes cold-water vibriosis in farmed Atlantic salmon. Its genome encodes Spot 42 with 84% identity to E. coli Spot 42. RESULTS: We generated a A. salmonicida spf deletion mutant. We then used microarray and Northern blot analyses to monitor global effects on the transcriptome in order to provide insights into the biological roles of Spot 42 in this bacterium. In the presence of glucose, we found a surprisingly large number of ≥ 2X differentially expressed genes, and several major cellular processes were affected. A gene encoding a pirin-like protein showed an on/off expression pattern in the presence/absence of Spot 42, which suggests that Spot 42 plays a key regulatory role in the central metabolism by regulating the switch between fermentation and respiration. Interestingly, we discovered an sRNA named VSsrna24, which is encoded immediately downstream of spf. This new sRNA has an expression pattern opposite to that of Spot 42, and its expression is repressed by glucose. CONCLUSIONS: We hypothesize that Spot 42 plays a key role in the central metabolism, in part by regulating the pyruvat dehydrogenase enzyme complex via pirin.
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Aliivibrio salmonicida/metabolismo , Proteínas de Bactérias/genética , Perfilação da Expressão Gênica , RNA/metabolismo , Aliivibrio salmonicida/genética , Proteínas de Bactérias/metabolismo , Sequência de Bases , Northern Blotting , Dados de Sequência Molecular , Análise de Sequência com Séries de Oligonucleotídeos , Alinhamento de SequênciaRESUMO
Patients with locally advanced rectal cancer often receive preoperative radio-chemotherapy (RCT). The mechanisms of tumour response to radiotherapy are not understood. The aim of this study was to identify the effects of RCT on gene expression in rectal tumour and normal rectal tissue. For that purpose tissue samples from 21 patients with resectable adenocarcinomas were collected for use in whole genome-microarray based gene expression analysis. A factorial experimental design allowed us to determine the effect of RCT on tumour tissue alone by removing the effect of radiation on normal tissue. This resulted in 1327 differentially expressed genes in tumour tissue with p<0.05. In addition to known markers for radio-chemotherapy, a Gene Set Enrichment Analysis (GSEA) showed a significant enrichment in gene sets associated with cell adhesion and leukocyte transendothelial migration. The profound change of cell adhesion molecule expression in rectal tumour tissue could either increase the risk of metastasis, or decrease the tumour's invasive potential.