Analysis Of Altered Gene Expression Research Articles

Systematic analysis of gene expression alterations and clinical outcomes of STAT3 in cancer.

Accumulated studies have provided controversial evidences of prognostic value for signal transducer and activator of transcription proteins 3 (STAT3) in cancers. To address this inconsistency, we performed a systematic analysis to determine whether STAT3 can serve as a prognostic marker in human cancers. STAT3 expression was assessed using Oncomine analysis. cBioPortal, Kaplan-Meier Plotter, and Prognoscan were performed to identify the prognostic roles of STAT3 in human cancers. The copy number alteration, mutation, interactive analysis, and visualize the altered networks were performed by cBioPortal. We found that STAT3 was more frequently overexpressed in lung, ovarian, gastric, blood and brain cancers than their normal tissues and its expression might be negatively related with the prognosis. In addition, STAT3 mutation mainly occurred in uterine cancer and existed in a hotspot in SH2 domain. Those findings suggest that STAT3 might serve as a diagnostic and therapeutic target for certain types of cancer, such as lung, ovarian, gastric, blood and brain cancers. However, future research is required to validate our findings and thus promote the clinical utility of STAT3 in those cancers prognosis evaluation.

Bioinformatics analysis of gene expression alterations conferring drug resistance in tumor samples from melanoma patients with EGFR-activating BRAF mutations.

Melanoma is a highly malignant tumor of the skin melanocytes. Patients with this cancer have a high frequency (~50%) of oncogenic BRAF mutations, particularly BRAF V600E. Treatments for melanoma often target BRAF mutations or involve mitogen-activated protein kinase kinase/extracellular signal-regulated kinase inhibitors. A major challenge in melanoma treatment is resistance to BRAF inhibitor treatment, which may be enhanced by the BRAF mutation itself and/or epidermal growth factor receptor (EGFR) activation, leading to poor prognosis. However, no effective clinical treatment exists for patients with EGFR-activating feedback. The aim of the present study was to analyze gene expression changes in tumors from patients with EGFR-activating BRAF mutations during development of drug resistance. RNA-seq data was downloaded from the Gene Expression Omnibus (GEO) database for pre- and post-treatment tumor samples from three melanoma patients with EGFR-activating BRAF V600E mutations, and from The Cancer Genome Atlas (TCGA) melanoma database for tumor and non-tumor samples from patients with the BRAF V600E mutation and unknown EGFR activation status. Using functional enrichment and KEGG pathway analyses, the present study analyzed differentially expressed genes (DEGs) between pre- vs. post-treatment data from the GEO database and tumor or non-tumor sample data from the TCGA database. The results of the present study indicated that functional and structural changes to the plasma membrane may be associated with drug resistance. The present study identified 9 DEGs that were significantly different between tumor and non-tumor samples and also between prior to and following treatment. Thus, it was confirmed that patients with EGFR-activating BRAF V600E mutations undergo gene expression changes during disease development, and during therapy. These findings may provide potential directions for melanoma-specific therapy.

Bioinformatics analysis of gene expression alterations in microRNA‑122 knockout mice with hepatocellular carcinoma.

Reduced microRNA (miR)-122 expression levels are frequently observed in hepatocellular carcinoma (HCC). The present study was conducted to investigate potential targets of miR-122 and determine the underlying regulatory mechanisms of miR-122 in HCC development. The public dataset GSE31731 was utilized, consisting of 8 miR-122 knockout (KO) mice (miR-122 KO) and 8 age-matched wild-type mice (WT group). Following data preprocessing, the differentially expressed genes (DEGs) were selected, followed by enrichment analysis. A protein-protein interaction (PPI) network was established, and a module network was further extracted. Combining the DEGs with microRNA targeting databases permitted the screening of the overlapping targets of miR-122. Furthermore, previously reported genes were screened out by literature mining. Transcription factors (TFs) of the targets were subsequently investigated. DEGs between miR-122 KO and WT groups were selected, including 713 upregulated and 395 downregulated genes. Of these, upregulated genes were enriched in cell cycle-associated processes [including nucleolar and spindle associated protein 1 (NUSAP1)], the cytokine-cytokine receptor interaction pathway [including C-X-C motif chemokine receptor 4 (CXCR4) and C-C motif chemokine receptor 2 (CCR2)], and the extracellular matrix-receptor interaction pathway [including integrin subunit alpha V (ITGAV)]. In addition, multiple overlapping targets were highlighted in the PPI network, including NUSAP1, CXCR4, CCR2 and ITGAV. Notably, CXCR4 and CCR2 were linked in module C, enriched in the cytokine-cytokine receptor interaction pathway. Furthermore, upregulated sex determining region Y-box 4 (SOX4) was identified as a TF. The results of the present study may provide a theoretical basis for further studies on the mechanisms of miR-122 in the development of HCC.

Systematic analysis of gene expression alterations and clinical outcomes of adenylate cyclase-associated protein in cancer.

Adenylate Cyclase-associated protein (CAP) is an evolutionarily conserved protein that regulates actin dynamics. Our previous study indicates that CAP1 is overexpressed in NSCLC tissues and correlated with poor clinical outcomes, but CAP1 in HeLa cells actually inhibited migration and invasion, the role of CAP was discrepancy in different cancer types. The present study aims to determine whether CAP can serve as a prognostic marker in human cancers. The CAP expression was assessed using Oncomine database to determine the gene alteration during carcinogenesis, the copy number alteration, or mutations of CAP using cBioPortal, International Cancer Genome Consortium, and Tumorscape database investigated, and the association between CAP expression and the survival of cancer patient using Kaplan-Meier plotter and PrognoScan database evaluated. Therefore, the functional correlation between CAP expression and cancer phenotypes can be established; wherein CAP might serve as a diagnostic marker or therapeutic target for certain types of cancers.

Systematic Analysis of Gene Expression Alterations and Clinical Outcomes for Long-Chain Acyl-Coenzyme A Synthetase Family in Cancer.

Dysregulated lipid metabolism contributes to cancer progression. Our previous study indicates that long-chain fatty acyl-Co A synthetase (ACSL) 3 is essential for lipid upregulation induced by endoplasmic reticulum stress. In this report, we aimed to identify the role of ACSL family in cancer with systematic analysis and in vitro experiment. We explored the ACSL expression using Oncomine database to determine the gene alteration during carcinogenesis and identified the association between ACSL expression and the survival of cancer patient using PrognoScan database. ACSL1 may play a potential oncogenic role in colorectal and breast cancer and play a potential tumor suppressor role in lung cancer. Co-expression analysis revealed that ACSL1 was coexpressed with MYBPH, PTPRE, PFKFB3, SOCS3 in colon cancer and with LRRFIP1, TSC22D1 in lung cancer. In accordance with PrognoScan analysis, downregulation of ACSL1 in colon and breast cancer cell line inhibited proliferation, migration, and anchorage-independent growth. In contrast, increase of oncogenic property was observed in lung cancer cell line by attenuating ACSL1. High ACSL3 expression predicted a better prognosis in ovarian cancer; in contrast, high ACSL3 predicted a worse prognosis in melanoma. ACSL3 was coexpressed with SNUPN, TRIP13, and SEMA5A in melanoma. High expression of ACSL4 predicted a worse prognosis in colorectal cancer, but predicted better prognosis in breast, brain and lung cancer. ACSL4 was coexpressed with SERPIN2, HNRNPCL1, ITIH2, PROCR, LRRFIP1. High expression of ACSL5 predicted good prognosis in breast, ovarian, and lung cancers. ACSL5 was coexpressed with TMEM140, TAPBPL, BIRC3, PTPRE, and SERPINB1. Low ACSL6 predicted a worse prognosis in acute myeloid leukemia. ACSL6 was coexpressed with SOX6 and DARC. Altogether, different members of ACSLs are implicated in diverse types of cancer development. ACSL-coexpressed molecules may be used to further investigate the role of ACSL family in individual type of cancers.

Dorsal root ganglion transcriptome analysis following peripheral nerve injury in mice.

BackgroundPeripheral nerve injury leads to changes in gene expression in primary sensory neurons of the injured dorsal root ganglia. These changes are believed to be involved in neuropathic pain genesis. Previously, these changes have been identified using gene microarrays or next generation RNA sequencing with poly-A tail selection, but these approaches cannot provide a more thorough analysis of gene expression alterations after nerve injury.MethodsThe present study chose to eliminate mRNA poly-A tail selection and perform strand-specific next generation RNA sequencing to analyze whole transcriptomes in the injured dorsal root ganglia following spinal nerve ligation. Quantitative real-time reverse transcriptase polymerase chain reaction assay was carried out to verify the changes of some differentially expressed RNAs in the injured dorsal root ganglia after spinal nerve ligation.ResultsOur results showed that more than 50 million (M) paired mapped sequences with strand information were yielded in each group (51.87 M–56.12 M in sham vs. 51.08 M–57.99 M in spinal nerve ligation). Six days after spinal nerve ligation, expression levels of 11,163 out of a total of 27,463 identified genes in the injured dorsal root ganglia significantly changed, of which 52.14% were upregulated and 47.86% downregulated. The largest transcriptional changes were observed in protein-coding genes (91.5%) followed by noncoding RNAs. Within 944 differentially expressed noncoding RNAs, the most significant changes were seen in long interspersed noncoding RNAs followed by antisense RNAs, processed transcripts, and pseudogenes. We observed a notable proportion of reads aligning to intronic regions in both groups (44.0% in sham vs. 49.6% in spinal nerve ligation). Using quantitative real-time polymerase chain reaction, we confirmed consistent differential expression of selected genes including Kcna2, Oprm1 as well as lncRNAs Gm21781 and 4732491K20Rik following spinal nerve ligation.ConclusionOur findings suggest that next generation RNA sequencing can be used as a promising approach to analyze the changes of whole transcriptomes in dorsal root ganglia following nerve injury and to possibly identify new targets for prevention and treatment of neuropathic pain.

Genomic-Wide Analysis with Microarrays in Human Oncology.

DNA microarray technologies have advanced rapidly and had a profound impact on examining gene expression on a genomic scale in research. This review discusses the history and development of microarray and DNA chip devices, and specific microarrays are described along with their methods and applications. In particular, microarrays have detected many novel cancer-related genes by comparing cancer tissues and non-cancerous tissues in oncological research. Recently, new methods have been in development, such as the double-combination array and triple-combination array, which allow more effective analysis of gene expression and epigenetic changes. Analysis of gene expression alterations in precancerous regions compared with normal regions and array analysis in drug-resistance cancer tissues are also successfully performed. Compared with next-generation sequencing, a similar method of genome analysis, several important differences distinguish these techniques and their applications. Development of novel microarray technologies is expected to contribute to further cancer research.

Gene expression profiling of brains from bovine spongiform encephalopathy (BSE)-infected cynomolgus macaques.

BackgroundPrion diseases are fatal neurodegenerative disorders whose pathogenesis mechanisms are not fully understood. In this context, the analysis of gene expression alterations occurring in prion-infected animals represents a powerful tool that may contribute to unravel the molecular basis of prion diseases and therefore discover novel potential targets for diagnosis and therapeutics. Here we present the first large-scale transcriptional profiling of brains from BSE-infected cynomolgus macaques, which are an excellent model for human prion disorders.ResultsThe study was conducted using the GeneChip® Rhesus Macaque Genome Array and revealed 300 transcripts with expression changes greater than twofold. Among these, the bioinformatics analysis identified 86 genes with known functions, most of which are involved in cellular development, cell death and survival, lipid homeostasis, and acute phase response signaling. RT-qPCR was performed on selected gene transcripts in order to validate the differential expression in infected animals versus controls. The results obtained with the microarray technology were confirmed and a gene signature was identified. In brief, HBB and HBA2 were down-regulated in infected macaques, whereas TTR, APOC1 and SERPINA3 were up-regulated.ConclusionsSome genes involved in oxygen or lipid transport and in innate immunity were found to be dysregulated in prion infected macaques. These genes are known to be involved in other neurodegenerative disorders such as Alzheimer’s and Parkinson’s diseases. Our results may facilitate the identification of potential disease biomarkers for many neurodegenerative diseases.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2164-15-434) contains supplementary material, which is available to authorized users.

The Oral Intake of Organic Germanium, Ge-132, Elevates α-Tocopherol Levels in the Plas-ma and Modulates Hepatic Gene Expression Profiles to Promote Immune Activation in Mice.

The common water-soluble organic germanium compound poly-trans-[(2-carboxyethyl) germasesquioxane] (Ge-132) exhibits activities related to immune responses and antioxidant induction. In this study, we evaluated the antioxidative effect of dietary Ge-132 in the plasma of mice. Male ICR mice (seven mice per group) received an AIN-76 diet with 0.05% Ge-132; three groups received the Ge-132-containing diet for 0, 1 or 4 days. The plasma alpha-tocopherol (α-tocopherol) concentration increased from 6.85 to 9.60 μg/ml after 4 days of Ge-132 intake (p<0.05). We evaluated the changes in hepatic gene expression related to antioxidative activity as well as in the entire expression profile after one day of Ge-132 intake, using DNA microarray technology. We identified 1,220 genes with altered expression levels greater than 1.5-fold (increased or decreased) as a result of Ge-132 intake, and α-tocopherol transfer protein (Ttpa) gene expression was increased 1.62-fold. Immune activation was identified as the category with the most changes (containing 60 Gene Ontology (GO) term biological processes (BPs), 41 genes) via functional clustering analysis of altered gene expression. Ge-132 affected genes in clusters related to ATP production (22 GO term BPs, 21 genes), lipid metabolism (4 GO term BPs, 38 genes) and apoptosis (5 GO term BPs). Many GO term BPs containing these categories were significantly affected by the Ge-132 intake. Oral Ge-132 intake may therefore have increased plasma α-tocopherol levels by up-regulating α-tocopherol transfer protein (Ttpa) gene expression.

Erythropoietin induces angiogenesis in a manner dependent on the intrinsic auto/paracrine production of interleukin-6 in vitro

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The role of Toll-like receptor 2 and hypoxia-induced transcription factor-1α in the atrial structural remodeling of non-valvular atrial fibrillation

Atrial fibrillation (AF) is the most common clinically significant cardiac arrhythmia. It is associated with an increased risk of ischemic stroke [ [1] Go A.S. Hylex E.M. Phillips K.A. et al. Prevalence of diagnosed a atrial fibrillation in adults: national implications for rhythm management and stroke prevention: the AnTicoagulation and Risk Factors in Atrial Fibrillation (ATRIA) Study. JAMA. 2001; 285: 2370-2375 Crossref PubMed Scopus (5058) Google Scholar ]. A growing evidence suggests a possible association between inflammation and atrial fibrillation (AF) [ 2 Aviles R.J. Martin D.O. Apperson-Hansen C. et al. Inflammation as a risk factor for atrial fibrillation. Circulation. 2003; 108: 3006-3010 Crossref PubMed Scopus (1118) Google Scholar , 3 Chung M.K. Martin D.O. Sprecher D. et al. C-reactive protein elevation in patients with atrial arrhythmias: inflammatory mechanisms and persistence of atrial fibrillation. Circulation. 2001; 104: 2886-2891 Crossref PubMed Scopus (1123) Google Scholar ]. Atrial biopsies of non-valvular AF patients also have provided the evidence that inflammation may participate in the pathogenesis of AF [ [4] Sekiguchi A. Yamashita T. Iwasaki Y. et al. Innate and adaptive immune reactions during progression of atrial fibrillation in humans. Jpn Circ J. 2008; 72: S514 Google Scholar ]. Recently, studies have demonstrated the changes in expression of gap junctions and activity of MMPs cause structural changes in the atrium that contribute to the pathogenesis of sustained AF. MMP-9 plays an important role in the degradation and remodeling of damaged tissues, including that of the heart [ 5 Polontchouk L. Haefliger J.A. Ebelt B. et al. Effects of chronic atrial fibrillation on gap junction distribution in human and rat atria. J Am Coll Cardiol. 2001; 38: 883-891 Crossref PubMed Scopus (228) Google Scholar , 6 Arndt M. Lendeckel U. Röcken C. et al. Altered expression of ADAMs (a disintegrin and metalloproteinase) in fibrillating human atria. Circulation. 2002; 105: 720-725 Crossref PubMed Scopus (78) Google Scholar , 7 Nakano Y. Niida S. Dote K. et al. Matrix metalloproteinase-9 contributes to human atrial remodeling during atrial fibrillation. J Am Coll Cardiol. 2004; 43: 818-825 Crossref PubMed Scopus (124) Google Scholar ]. However, the role of Toll-like receptor 2 (TLR2) and hypoxia-induced transcription factor-1α (HIF-1α) as immunological and inflammatory factor in atria structural remodeling of non-valvular AF has not been clarified [ 8 Pons J. Sauleda J. Regueiro V. et al. Expression of Toll-like receptor 2 is up-regulated in monocytes from patients with chronic obstructive pulmonary disease. Respir Res. 2006; 7: 64 Crossref PubMed Scopus (68) Google Scholar , 9 Harter L. Mica L. Stocker R. et al. Increased expression of toll-like receptor-2 and -4 on leukocytes from patients with sepsis. Shock. 2004; 22: 403-409 Crossref PubMed Scopus (106) Google Scholar , 10 Thijssen V.L. van der Velden H.M. van Ankeren E.P. et al. Analysis of altered gene expression during sustained atrial fibrillation in the goat. Cardiovasc Res. 2002; 54: 427-437 Crossref PubMed Scopus (38) Google Scholar ].

Global transcriptome analysis of two ameiotic1 alleles in maize anthers: defining steps in meiotic entry and progression through prophase I

BackgroundDevelopmental cues to start meiosis occur late in plants. Ameiotic1 (Am1) encodes a plant-specific nuclear protein (AM1) required for meiotic entry and progression through early prophase I. Pollen mother cells (PMCs) remain mitotic in most am1 mutants including am1-489, while am1-praI permits meiotic entry but PMCs arrest at the leptotene/zygotene (L/Z) transition, defining the roles of AM1 protein in two distinct steps of meiosis. To gain more insights into the roles of AM1 in the transcriptional pre-meiotic and meiotic programs, we report here an in depth analysis of gene expression alterations in carefully staged anthers at 1 mm (meiotic entry) and 1.5 mm (L/Z) caused by each of these am1 alleles.Results1.0 mm and 1.5 mm anthers of am1-489 and am1-praI were profiled in comparison to fertile siblings on Agilent® 4 × 44 K microarrays. Both am1-489 and am1-praI anthers are cytologically normal at 1.0 mm and show moderate transcriptome alterations. At the 1.5-mm stage both mutants are aberrant cytologically, and show more drastic transcriptome changes. There are substantially more absolute On/Off and twice as many differentially expressed genes (sterile versus fertile) in am1-489 than in am1-praI. At 1.5 mm a total of 4,418 genes are up- or down-regulated in either am1-489 or am1-praI anthers. These are predominantly stage-specific transcripts. Many putative meiosis-related genes were found among them including a small subset of allele-specific, mis-regulated genes specific to the PMCs. Nearly 60% of transcriptome changes in the set of transcripts mis-regulated in both mutants (N = 530) are enriched in PMCs, and only 1% are enriched in the tapetal cell transcriptome. All array data reported herein will be deposited and accessible at MaizeGDB http://www.maizegdb.org/.ConclusionsOur analysis of anther transcriptome modulations by two distinct am1 alleles, am1-489 and am1-praI, redefines the role of AM1 as a modulator of expression of a subset of meiotic genes, important for meiotic progression and provided stage-specific insights into the genetic networks associated with meiotic entry and early prophase I progression.

Neuroinflammation and parkinson’s disease: Quantitative analysis of gene expression alterations in the substantia nigra of mice exposed to MPTP or LPS with a custom qPCR array

Neuroinflammation and parkinson’s disease: Quantitative analysis of gene expression alterations in the substantia nigra of mice exposed to MPTP or LPS with a custom qPCR array

Acute Hepatotoxicity: A Predictive Model Based on Focused Illumina Microarrays

Drug-induced hepatotoxicity is a major issue for drug development, and toxicogenomics has the potential to predict toxicity during early toxicity screening. A bead-based Illumina oligonucleotide microarray containing 550 liver specific genes has been developed. We have established a predictive screening system for acute hepatotoxicity by analyzing differential gene expression profiles of well-known hepatotoxic and nonhepatotoxic compounds. Low and high doses of tetracycline, carbon tetrachloride (CCL4), 1-naphthylisothiocyanate (ANIT), erythromycin estolate, acetaminophen (AAP), or chloroform as hepatotoxicants, clofibrate, theophylline, naloxone, estradiol, quinidine, or dexamethasone as nonhepatotoxic compounds, were administered as a single dose to male Sprague-Dawley rats. After 6, 24, and 72 h, livers were taken for histopathological evaluation and for analysis of gene expression alterations. All hepatotoxic compounds tested generated individual gene expression profiles. Based on leave-one-out cross-validation analysis, gene expression profiling allowed the accurate discrimination of all model compounds, 24 h after high dose treatment. Even during the regeneration phase, 72 h after treatment, CCL4, ANIT, and AAP were predicted to be hepatotoxic, and only these three compounds showed histopathological changes at this time. Furthermore, we identified 64 potential marker genes responsible for class prediction, which reflected typical hepatotoxicity responses. These genes and pathways, commonly deregulated by hepatotoxicants, may be indicative of the early characterization of hepatotoxicity and possibly predictive of later hepatotoxicity onset. Two unknown test compounds were used for prevalidating the screening test system, with both being correctly predicted. We conclude that focused gene microarrays are sufficient to classify compounds with respect to toxicity prediction.

Transcriptional Profiles in Liver from Rats Treated with Tumorigenic and Non-tumorigenic Triazole Conazole Fungicides: Propiconazole, Triadimefon, and Myclobutanil

Conazoles are a class of fungicides used as pharmaceutical and agricultural agents. In chronic bioassays in rats, triadimefon was hepatotoxic and induced follicular cell adenomas in the thyroid gland, whereas, propiconazole and myclobutanil were hepatotoxic but had no effect on the thyroid gland. These conazoles administered in the feed to male Wistar/Han rats were found to induce hepatomegaly, induce high levels of pentoxyresorufin-O-dealkylase, increase cell proliferation in the liver, increase serum cholesterol, decrease serum T3 and T4, and increase hepatic uridine diphosphoglucuronosyl transferase activity. The goal of the present study was to define pathways that explain the biologic outcomes. Male Wistar/Han rats (3 per group), were exposed to the 3 conazoles in the feed for 4, 30, or 90 days of treatment at tumorigenic and nontumorigenic doses. Hepatic gene expression was determined using high-density Affymetrix GeneChips (Rat 230_2). Differential gene expression was assessed at the probe level using Robust Multichip Average analysis. Principal component analysis by treatment and time showed within group sample similarity and that the treatment groups were distinct from each other. The number of altered genes varied by treatment, dose, and time. The greatest number of altered genes was induced by triadimefon and propiconazole after 90 days of treatment, while myclobutanil had minimal effects at that time point. Pathway level analyses revealed that after 90 days of treatment the most significant numbers of altered pathways were related to cell signaling, growth, and metabolism. Pathway level analysis for triadimefon and propiconazole resulted in 71 altered pathways common to both chemicals. These pathways controlled cholesterol metabolism, activation of nuclear receptors, and N-ras and K-ras signaling. There were 37 pathways uniquely changed by propiconazole, and triadimefon uniquely altered 34 pathways. Pathway level analysis of altered gene expression resulted in a more complete description of the associated toxicological effects that can distinguish triadimefon from propiconazole and myclobutanil.

Analysis of interleukin‐1β‐modulated mRNA gene transcription in human gingival keratinocytes by epithelia‐specific cDNA microarrays

Proinflammatory cytokines such as interleukin-1beta are known to be synthesized in oral gingivitis and periodontitis and lead to the activation of the transcription factor nuclear factor-kappaB (NF-kappaB). Although numerous effects of interleukin-1beta on mesenchymal cells are known, e.g. up-regulation of intercellular adhesion molecule-1 in endothelial cells, little is known of the effects of interleukin-1beta on oral keratinocytes. The purpose of the present study was to seek interleukin-1beta-mediated alterations in mRNA gene transcription and a putative activation of NF-kappaB in oral gingival keratinocytes. As an in vitro model for gingivitis and periodontitis, immortalized human gingival keratinocytes (IHGK) were stimulated with the proinflammatory cytokine interleukin-1beta. An epithelia-specific cDNA microarray was used to analyze mRNA expression profiles from IHGK cells treated with 200 units interleukin-1beta/ml for 3, 6, 9, 12, and 24 h. Indirect immunofluorescence was carried out to detect NF-kappaB in IHGK following interleukin-1beta treatment. Detailed analysis revealed distinct patterns of time-dependent changes, including genes induced or repressed early (3-6 h) or late (12-24 h) after interleukin-1beta treatment. Differentially expressed genes were involved in (i) cell stress, (ii) DNA repair, (iii) cell cycle and proliferation, (iv) anti-pathogen response, (v) extracellular matrix turnover, and (vi) angiogenesis. A large number of genes were responsive to NF-kappaB and induction was concomitant with nuclear translocation of the p65 RelA subunit of NF-kappaB. Interestingly, many of these genes contain multiple NF-kappaB binding sites in their promoters. Analysis of altered gene expression allows identification of gene networks associated with inflammatory responses. In addition to a number of well-known genes involved in gingivitis and periodontitis, we identified novel candidates that might be associated with the onset and maintenance of an inflammatory disease.

Differential expression profiling of genes in a complete hydatidiform mole using cDNA microarray analysis

Objectives. To gain a better understanding of the genes involved in the pathogenesis of gestational trophoblastic diseases, we evaluated the genome-wide expression levels of genes in complete hydatidiform mole (H-mole) as compared to normal placenta using cDNA microarray technique. Methods. The expression profiles of complete H-mole tissues were compared with those of normal placenta using cDNA microarray technique. The data obtained from 10,305 human genes were normalized by the print-tip-based LOWESS method. Significance analysis of microarray (SAM) was used to identify genes with statistically significant changes in expression. The expression levels of genes which showed significant differences between normal early placenta and complete H-mole tissues were further confirmed by RT-PCR. Results. A cDNA microarray analysis consisting of 10,305 human genes revealed significant changes in the expression of 213 genes, with 91 genes being upregulated and 122 being downregulated. SAM revealed significant changes in gene expression, including those associated with signal transduction, cell structure, transcription, and apoptosis. Further RT-PCR analysis of altered gene expression in mole tissues supported the microarray analysis results. We confirmed the upregulation of TLE4, CAPZA1, PRSS25, RNF130, and USP1 in complete H-mole tissues. Moreover, our study provides the first evidence that ELK3, LAMA3, LNK, STAT2, and TNFRSF25 are downregulated in complete H-mole compared to normal early placenta tissues. Conclusions. These findings provide a large body of information regarding gene expression profiles associated with complete H-mole tumorigenesis and allow the identification of potential targets for tumor prevention or therapy.

Differentially Expressed Genes in Hemocytes of Vibrio harveyi-challenged Shrimp Penaeus monodon

Differential Display PCR technique (DD-PCR) was used for the analysis of altered gene expression in hemocytes of Vibrio harveyi-infected Penaeus monodon. Forty-four combinations of arbitrary and oligo(dT) primers were used to screen for differentially expressed genes. A total of 79 differentially expressed bands could be identified from 33 primer combinations. These included 48 bands (61%) whose expression level increased and 31 bands (39%) decreased after V. harveyi challenge. Subsequently, forty-eight differential display fragments were successfully reamplified and cloned. A total of 267 clones were randomly selected and sequenced. The sequence analysis showed that 85 (31%) out of 267 clones were matched with sequences in the GenBank database which represented 24 different genes with known functions. Among the known genes, glucose transporter 1, interferon-related developmental regulator 1, lysozyme, profilin, SERPINB3, were selected for further confirmation of their differentially expression patterns by real-time PCR. The results showed increasing in expression level of the selected genes in shrimp hemocytes after microbial challenge suggesting the involvement of such genes in bacterial response in shrimp. The anti-lipopolysaccharide factor type 3 (ALFPm3) gene, previously reported in P. monodon (Supungul et al., 2002) was found among the up-regulated genes but diversity due to amino acid changes was observed. Increase in ALFPm3 transcripts upon V. harveyi injection is in accordance with that found in the previous study.

CDNA array analysis of gene expression alterations in the early stage of colorectal carcinogenesis and search for molecular tumor marker

cDNA array analysis of gene expression alterations in the early stage of colorectal carcinogenesis and search for molecular tumor marker

Global analysis of altered gene expression during morphogenesis of Candida albicans in vitro

Candida albicans, a commensal of the gastrointestinal and uro vaginal tract can cause life-threatening infections under conditions of lowered immunity of the host. The changes in the host environment that are sensed by the pathogen which elicit this response have not yet been clearly identified. We report here that co-incubation with a macrophage cell line in vitro for extended period of time (16 h) leads to lysis of the macrophage cells. The altered condition in growth medium induces differential gene expression of sets of genes. Specifically genes involved in galactose, protein, and lipid metabolism and stress response undergo concerted changes in their transcript levels. Promoter analysis of differentially expressed genes revealed presence of CPH1 and EFG1 transcription factor binding sites. Based on the gene expression profiles and mutant studies we propose that this morphogenetic response of C. albicans under the conditions used in these experiments is mainly through the pathways controlled by the above two regulators and not through the RIM101-dependent pathway.