scholarly journals Gene Expression Pattern and Regulatory Network of α-Toxin Treatment in Bombyx mori

2019 ◽  
Vol 2019 ◽  
pp. 1-11
Author(s):  
Tieshan Feng ◽  
Ping Lin ◽  
Jiao Gong ◽  
Dong Cheng ◽  
Xi Yang ◽  
...  

Bacillus bombyseptieus is a pathogen of Bombyx mori; it can cause bacterial septicemia in silkworm. One of the components of the parasporal crystal toxin of B. bombyseptieus, α-toxin, plays an important role in the process of infection in silkworm. In this study, we investigated the immune response of silkworm induced by α-toxin by using RNA-seq. We compared the changes in gene expression in the midgut, fatbody, and hemocytes of silkworm and in the B. mori embryonic cell line (BmE) after treatment with α-toxin and identified 952 differentially expressed genes and 353 differentially expressed long noncoding RNAs (lncRNAs). These regulated genes in different tissues were found to be enriched in different pathways. The upregulated genes in the midgut were mainly involved in peptidoglycan catabolic process and tyrosine kinase signaling pathway, whereas the downregulated genes were mainly involved in chitin metabolic pathways. The upregulated genes in fatbody were also involved in peptidoglycan catabolic process, but they were for a different peptidoglycan subtype. Further, genes encoding cecropins were enriched in the fatbody. The downregulated genes were mainly involved in the metabolic pathways of fundamental substances such as cellular protein metabolic process and nucleobase-containing compound metabolic process. These results suggest that α-toxin can induce various immune responses in silkworm, and further studies are warranted to understand the mechanism of α-toxin action in silkworm. Further, lncRNAs and differentially expressed genes were correlated using coexpression network analysis. Our findings revealed potential candidate genes and lncRNAs that might play important physiological functions in the immune response to α-toxins in silkworm.

2012 ◽  
Vol 44 (22) ◽  
pp. 1098-1106 ◽  
Author(s):  
Mohamed T. Ghorbel ◽  
Amir Mokhtari ◽  
Maimuna Sheikh ◽  
Gianni D. Angelini ◽  
Massimo Caputo

In cyanotic patients undergoing repair of heart defects, high level of oxygen during cardiopulmonary bypass (CPB) leads to greater susceptibility to myocardial ischemia and reoxygenation injury. This study investigates the effects of controlled reoxygenation CPB on gene expression changes in cyanotic hearts of patients undergoing surgical correction of tetralogy of Fallot (TOF). We randomized 49 cyanotic TOF patients undergoing corrective cardiac surgery to receive either controlled reoxygenation or hyperoxic/standard CPB. Ventricular myocardium biopsies were obtained immediately after starting and before discontinuing CPB. Microarray analyses were performed on samples, and array results validated with real-time PCR. Gene expression profiles before and after hyperoxic/standard CPB revealed 35 differentially expressed genes with three upregulated and 32 downregulated. Upregulated genes included two E3 Ubiquitin ligases. The products of downregulated genes included intracellular signaling kinases, metabolic process proteins, and transport factors. In contrast, gene expression profiles before and after controlled reoxygenation CPB revealed only 11 differentially expressed genes with 10 upregulated including extracellular matrix proteins, transport factors, and one downregulated. The comparison of gene expression following hyperoxic/standard vs. controlled reoxygenation CPB revealed 59 differentially expressed genes, with six upregulated and 53 downregulated. Upregulated genes included PDE1A, MOSC1, and CRIP3. Downregulated genes functionally clustered into four major classes: extracellular matrix/cell adhesion, transcription, transport, and cellular metabolic process. This study provides direct evidence that hyperoxic CPB decreases the adaptation and remodeling capacity in cyanotic patients undergoing TOF repair. This simple CPB strategy of controlled reoxygenation reduced the number of genes whose expression was altered following hyperoxic/standard CPB.


2008 ◽  
Vol 36 (1) ◽  
pp. 15-23 ◽  
Author(s):  
Pascal J. H. Smeets ◽  
Heleen M. de Vogel-van den Bosch ◽  
Peter H. M. Willemsen ◽  
Alphons P. Stassen ◽  
Torik Ayoubi ◽  
...  

Peroxisome proliferator-activated receptor (PPAR)α regulates lipid metabolism at the transcriptional level and modulates the expression of genes involved in inflammation, cell proliferation, and differentiation. Although PPARα has been shown to mitigate cardiac hypertrophy, knowledge about underlying mechanisms and the nature of signaling pathways involved is fragmentary and incomplete. The aim of this study was to identify the processes and signaling pathways regulated by PPARα in hearts challenged by a chronic pressure overload by means of whole genome transcriptomic analysis. PPARα−/− and wild-type mice were subjected to transverse aortic constriction (TAC) for 28 days, and left ventricular gene expression profile was determined with Affymetrix GeneChip Mouse Genome 430 2.0 arrays containing >45,000 probe sets. In unchallenged hearts, the mere lack of PPARα resulted in 821 differentially expressed genes, many of which are related to lipid metabolism and immune response. TAC resulted in a more pronounced cardiac hypertrophy and more extensive changes in gene expression (1,910 and 312 differentially expressed genes, respectively) in PPARα−/− mice than in wild-type mice. Many of the hypertrophy-related genes were related to development, signal transduction, actin filament organization, and collagen synthesis. Compared with wild-type hypertrophied hearts, PPARα−/− hypertrophied hearts revealed enrichment of gene clusters related to extracellular matrix remodeling, immune response, oxidative stress, and inflammatory signaling pathways. The present study therefore demonstrates that, in addition to lipid metabolism, PPARα is an important modulator of immune and inflammatory response in cardiac muscle.


2020 ◽  
Author(s):  
Wei Han ◽  
Guo-liang Shen

Abstract Background: Skin Cutaneous Melanoma (SKCM) is known as an aggressive malignant cancer, which could be directly derived from melanocytic nevi. However, the molecular mechanisms underlying malignant transformation of melanocytes and melanoma tumor progression still remain unclear. Increasing researches showed significant roles of epigenetic modifications, especially DNA methylation, in melanoma. This study focused on identification and analysis of methylation-regulated differentially expressed genes (MeDEGs) between melanocytic nevus and malignant melanoma in genome-wide profiles. Methods: The gene expression profiling datasets (GSE3189 and GSE114445) and gene methylation profiling datasets (GSE86355 and GSE120878) were downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) and differentially methylated genes (DMGs) were identified via GEO2R. MeDEGs were obtained by integrating the DEGs and DMGs. Then, functional enrichment analysis of MeDEGs were performed. STRING and Cytoscape were used to describe protein-protein interaction(PPI) network. Furthermore, survival analysis was implemented to select the prognostic hub genes. Finally, we conducted gene set enrichment analysis (GSEA) of hub genes. Results: We identified 237 hypomethylated, upregulated genes and 182 hypermethylated, downregulated genes. Hypomethylation-upregulated genes were enriched in biological processes of the oxidation-reduction process, cell proliferation, cell division, phosphorylation, extracellular matrix disassembly and protein sumoylation. Pathway enrichment showed selenocompound metabolism, small cell lung cancer and lysosome. Hypermethylation-downregulated genes were enriched in biological processes of positive regulation of transcription from RNA polymerase II promoter, cell adhesion, cell proliferation, positive regulation of transcription, DNA-templated and angiogenesis. The most significantly enriched pathways involved the transcriptional misregulation in cancer, circadian rhythm, tight junction, protein digestion and absorption and Hippo signaling pathway. After PPI establishment and survival analysis, seven prognostic hub genes were CKS2, DTL, KIF2C, KPNA2, MYBL2, TPX2 and FBL. Moreover, the most involved hallmarks obtained by GSEA were E2F targets, G2M checkpoint and mitotic spindle. Conclusions: Our study identified potential aberrantly methylated-differentially expressed genes participating in the process of malignant transformation from nevus to melanoma tissues based on comprehensive genomic profiles. Transcription profiles of CKS2, DTL, KIF2C, KPNA2, MYBL2, TPX2 and FBL provided clues of aberrantly methylation-based biomarkers, which might improve the development of precise medicine.


Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2435-2435
Author(s):  
Delphine Rossille ◽  
Céline Pangault ◽  
Xavier Cahu ◽  
Thierry Lamy ◽  
Burgun Anita ◽  
...  

Abstract Abstract 2435 DLBCLs are the most prevalent lymphomas in adults and great advances have been made in understanding molecular effects on tumor cells as well as tissue environment, leading to determining gene prognosis signatures using transcriptional profiling techniques. As blood cells interact with cells in almost all tissues in the body, blood-derived total RNA gene expressions have been investigated for the past years including for solid cancers [Clin Cancer Res. 2006:3374.], infections [Nature 2010;446:973.] and autoimmune disorders [Genes Immun. 2010;11:269., Immunity 2008;29:150.]. Blood-based microarray approaches were able to identify differentially expressed genes distinguishing patients from healthy volunteers. Interested in the potential of this noninvasive and easy-to-use technique, we hypothesized that aggressive DLBCLs at diagnosis cause molecular perturbations on the whole blood allowing identifying gene expression differentiation compared to healthy controls. Whole blood was collected into PAXgene™ Blood RNA tubes ensuring blood stabilization and sent within 24 hours to be stored at −80°C before extraction. Our study involved high-quality RNA samples from 75 DLBCL patients taken at diagnosis prior to any anti-cancer treatment and 87 healthy volunteers, sex and gender matched. All patients were less than 60 and enrolled in a multicentric & prospective clinical trial for aggressive form of DLBCL, GOELAMS 075, which compares the autologous stem cell treatment to regular R-CHOP procedure. The median age was 52 for patients and 48 for controls. Gene expression profiling (GEP) was assessed using Affymetrix GeneChip® Human Exon 1.0 ST arrays. Unsupervised hierarchical clustering analysis (HCA) distinguished DLBCLs from controls. Two gene lists were identified based on HCA (Figure 1): listA consisted in 3,323 upregulated genes for a subgroup of patients and inversely, listB in 2,966 upregulated genes for controls. Canonical pathways were generated for both lists for genes meeting p<5% and FC >1.2 through the use of IPA (Ingenuity® Systems). The upregulated genes for patients (listA) were found associated with cytokine signaling pathways (Interleukins, NF-κB) while the down-regulated genes (listB) were implicated in T lymphocytes signaling pathways. Further investigations of the dataset by univariate analysis (Mann-Whitney test, FDR<5%, FC >1.5) found 1047 differentially expressed genes, confirming the systemic alteration. A set of 20 genes, selected as the best predictive genes for which the misclassification error rate is minimal, was able to discriminate DLBCLs from control samples (sensitivity= 88% & specificity=95%). No correlation was found between genes and biological parameters such as hemoglobin, leucocytes, lymphocytes, platelets or polynuclear neutrophils. The down-regulated genes were located in the nucleus and involved in transcription deregulation, DNA repair and apoptosis. Upregulated genes were related to the immune response as well as the inflammatory response with for instance S100 proteins which are implicated in myeloid-derived suppressor cell biology. Conclusion: Despite the complex mixture of cell types in blood, whole blood has shown strong systemic perturbations in DLBCLs at diagnosis. Biological investigation indicated an over-expression of the inflammation and immune responses combined to perturbations of the T-lymphocyte pattern. Our findings concerning inflammation-related gene expression including NF-κB activation and upregulated cytokine transcripts, with for instance IL-1, IL-6 & IL-10, invite us to determine whether a specific DLBCL-induced inflammation process exists compared to other nonmalignant diseases [Clin Microbiol Rev. 2002 Jul; 15(3):414-29]. Comparison to other lymphoma and inflammatory diseases as well as with tumor status are under way allowing to better characterizing DLBCL-specific biomarkers. These results shed new lights on DLBCL biology deciphering disease's heterogeneity at the RNA whole blood level. They encourage us to investigate whole blood GEP for prognosis and as a new parameter useful for disease classification. Disclosures: No relevant conflicts of interest to declare.


2020 ◽  
Author(s):  
Zhongxiao Lu ◽  
Jian Wu ◽  
Yi-ming Li ◽  
Wen-xiang Chen ◽  
Qiang-feng Yu ◽  
...  

Abstract AimLiver cancer is a common malignant tumor whose molecular pathogenesis remains unclear. This study attempts to identify key genes related to liver cancer by bioinformatics analysis and analyze their biological functions.MethodsThe gene expression data of the microarray were downloaded from the Gene Expression Omnibus(GEO) database. The differentially expressed genes (DEGs) were then identified by the R software package “limma” and were subjected to gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses using DAVID. The protein-protein interaction (PPI) network was constructed via String, and the results were visualized in Cytoscape. Modules and hub genes were identified using the MCODE plugin, while the expression of hub genes and its effects were analyzed by GEPIA2. Additionally, the co-expression of the hub gene was explored in String, while the GO results were visualized using the R software. Finally, the targets of the hub gene were predicted through an online website. ResultsIn total, 43 differentially expressed genes were obtained. The GO analysis was mainly concentrated in the redox process and nuclear mitosis, while the KEGG pathway analysis was mainly enriched in retinol metabolism and the cell cycle. Moreover, four hub genes were identified in the PPI network, however, the Kaplan-Meier risk curve showed that only ECT2 and FCN3 affected the survival of liver cancer. ECT2 was found to be high expressed in liver cancer, carrying out signal transduction and targeting hsa-miR-27a-3p. FCN3 was observed to be lowly expressed in liver cancer and related to the immune response, targeting hsa-miR132-5p.ConclusionThe obtained findings suggest that two genes are significantly related to the prognosis of liver cancer, and the analysis of their biological function provided novel insight into the pathogenesis of liver cancer. Furthermore, FCN3 may serve as a promising biomarker for patients with liver cancer.


2019 ◽  
Author(s):  
Akanksha Rajput ◽  
Manoj Kumar

AbstractThe Nipah virus is responsible various outbreaks among countries of south east Asia, most recent is in Kerala, India. It is considered to be highly contagious and having a range of vectors for transmission. The condition worsens due to the lack of effective inhibitors. This study is first study, which focused to detect the differentially expressed genes among two different NiV studies from 2012 and 2017. The transcriptomic profiling data were retrieved from the sequence archives. The multivariate gene enrichment analyses were performed on the log transformed data from them using pathway, gene ontology, disease, reactome, etc. The comparison study suggests that the down regulated differentially expressed genes are common among them as compared to up regulated ones with statistical significance. However, among the diseased category the upregulated genes are mostly from metabolic pathways and diseased category like metabolic pathways, heart failure, cholesterol metabolism while the downregulated genes linked to various cancers, and viral diseases like hepatitis, dengue, influenza, etc. We found various small molecules mapped in the pathways which are differentially expressed among the studies, which could be targeted so as to control the Nipah infection. In order to design the inhibitors, our study would be useful to extract the effective and broad-spectrum drug targets.


2021 ◽  
Vol 12 ◽  
Author(s):  
Yueqin Guo ◽  
Qi Zhang ◽  
Xiao Hu ◽  
Chunxiu Pang ◽  
Jilian Li ◽  
...  

Bumblebee queens have remarkable spermathecae that store sperm for year-round reproduction. The spermathecal gland is regarded as a secretory organ that could benefit sperm storage. Queen mating provokes substantial physiological, behavioral, and gene expression changes. Here, the transcriptomes of spermathecae were compared between virgins and mated queens of the bumblebee, Bombus terrestris L., at 24 h post mating. Differentially expressed genes were further validated by real time quantitative PCR and immunofluorescence assay. In total, the expression of 11, 069 and 10, 862 genes were identified in virgins and mated queens, respectively. We identified that 176 differentially expressed genes between virgin and mated queen spermathecae: 110 (62.5%) genes were upregulated, and 66 (37.5%) genes were downregulated in mated queens. Most of the differentially expressed genes validated by RT-qPCR were concentrated on immune response [i.e., leucine-rich repeat-containing protein 70 (35.8-fold), phenoloxidase 2 (41.9-fold), and defensin (4.9-fold)] and sperm storage [i.e., chymotrypsin inhibitor (6.2-fold), trehalose transporter Tret1 (1.7-, 1.9-, 2.4-, and 2.4-fold), and heterogeneous nuclear ribonucleoprotein A3 (1.2-, and 2.6-fold)] functions in the spermathecae of mated queens. Procollagen-lysine, 2-oxoglutarate 5-dioxygenase 1 (PLOD1) was hypothesized to promote the mating behavior according to RT-qPCR and immunofluorescence assay. The expression levels of most upregulated immune genes were decreased significantly at 3 days post mating. In conclusion, the external sperm transfer into spermathecae led to the significantly upregulated immune response genes in bumblebees. These gene expression differences in queen spermathecae contribute to understanding the bumblebee post mating regulatory network.


Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1243-1243
Author(s):  
Amit K Mittal ◽  
Christine E Gilling ◽  
Javeed Iqbal ◽  
R. Gregory Bociek ◽  
Patricia Aoun ◽  
...  

Abstract Abstract 1243 Poster Board I-265 Chronic lymphocytic leukemia (CLL) is the most common adult leukemia and is clinically very heterogeneous. Following diagnosis, some patients do not require treatment for several years whereas others have a more aggressive disease thus requiring immediate treatment. Understanding the molecular basis of clinical heterogeneity in CLL will enhance our ability to treat this presently incurable disease effectively. CLL cells in the patient body proliferate/survive for a long time resulting in their accumulation in bone marrow (BM), lymph nodes (LN), and blood (PB). However, CLL cells do not survive for a long time once they are removed from the body, suggesting that an in vivo microenvironment provides essential proliferation/survival signals to CLL cells. Therefore, to elucidate the precise role of microenvironments on the CLL cell proliferation/survival and migration, in this study, we have analyzed CLL cells from PB (n=20), BM (n=18), and LN (n=15) from patients for their gene expression profiles using microarray. Differentially expressed genes and their associated cellular pathways were identified using significant analysis of microarray (SAM) and gene set enrichment analyses (GSEA). Among the six pathways/gene expression signatures identified (BCR-, BAFF/April-, NFκB-, PI3K/Akt, cytokine-, and tolerogenic) the most significant pathways in CLL biology are the BCR-, NFκB-, PI3K/Akt pathways and tolerogenic signature associated genes with immune dysregulation particularly with CLL cells from LN. We have already reported the differential expression of CLL cell proliferation and survival related genes belonging to BCR and NFαB pathways (Mittal et al, 2008 Blood-ASH Annual Meeting Abstract 546, page 112). In this report we have focused on differentially expressed genes associated with the tolerogenic signature and PI3K/Akt pathway. Among the eighty-three differentially expressed genes in the tolerogenic signature, based on their known role in immune regulation and/or level of significant expression comparing CLL cells from PB or BM, a few selected genes were further studied to understand their possible role in clinical heterogeneity of CLL. These genes are: CAV1, CD47, CCNB2, IL2Rαa, FOXP3, ZWINT, TGFβR1, IL22, IL10Rαa, INDO, APC, and STAT1. There was a significant increase in the expression of CD47, IL-10Rαa, CAV1, APC, CCNB2, and STAT1 in the LN cells from CLL patients; whereas the expression of IL-22R was decreased in the LN cells. These genes have been shown to be associated with immunosuppression indicating a lack of immune response against CLL in the lymph node. In addition, MAPK pathway associated genes are known to increase the survival/proliferation of tumor cells, including CLL cells. Specifically, genes associated with PI3K/Akt pathway, a part of MAPK pathways are also overexpressed in CLL cells from LN that includes AKT, 4E-BP1, PSMC4 and PDK1 genes indicating the importance of PI3K/Akt pathway in proliferation/survival of CLL cells in LN microenvironment. Based on these results, we hypothesize that differentially expressed genes belonging to the tolerogenic signature in LN of CLL patients down regulate the immune response against CLL, thus leading to enhanced disease progression whereas, overexpressed proliferation/survival-related genes belong to PI3K/Akt pathway promote proliferation/survival of CLL cells. (This work was supported by the CLL Foundation, Houston, TX and National Institutes of Health, Bethesda, MD, INBRE Grant # P20 RR016469). Disclosures No relevant conflicts of interest to declare.


2005 ◽  
Vol 42 (5) ◽  
pp. 550-558 ◽  
Author(s):  
S. A. M. Thomson ◽  
E. Kennerly ◽  
N. Olby ◽  
J. R. Mickelson ◽  
D. E. Hoffmann ◽  
...  

The pathophysiologic similarities of many human and canine cancers support the role of the domestic dog as a model for brain tumor research. Here we report the construction of a custom canine brain-specific cDNA microarray and the analysis of gene expression patterns of several different types of canine brain tumor The microarray contained 4000 clones from a canine brain specific cDNA library including 2161 clones that matched known genes or expressed sequence tags (ESTs) and 25 cancer-related genes. Our study included 16 brain tumors (seven meningiomas, five glial tumors, two ependymomas, and two choroid plexus papillomas) from a variety of different dog breeds. We identified several genes previously found to be differentially expressed in human brain tumors. This suggests that human and canine brain tumors share a common pathogenesis. In addition, we also found differentially expressed genes unique to either meningiomas or the glial tumors. This report represents the first global gene expression analysis of different types of canine brain tumors by cDNA microarrays and might aid in the identification of potential candidate genes involved in tumor formation and progression.


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