Identification of differentially expressed genes in nasopharyngeal carcinoma by means of the Atlas human cancer cDNA expression array.
ABSTRACT To investigate genes of critical areas, including cell cycle/growth control, apoptosis, oncogene/tumor suppressors and growth factor/cytokines, that are differentially expressed in nasopharyngeal carcinoma.
The Human Cancer cDNA Atlas, which contains 588 genes relating to tumor biology, was used to screen normal nasopharyngeal tissue, nasopharyngeal cancer (NPC). The reverse transcription/polymerase chain reaction was used to confirm the expression pattern of some genes identified by Atlas hybridization.
The differentially expressed cell cycle/growth control regulators in NPC showed a stronger tendency toward cell proliferation with the up-regulation of cyclin D1, cyclin D2 etc. The expression pattern of apoptosis-related genes demonstrated the up-regulation of both anti-apoptotic factors such as the BCL-2-related protein A1, TRAF3, the inhibitor of apoptosis protein A1 (IAPI) and apoptotic pathway elements such as Fas/Apo-1, Apo-2 ligand etc. Among oncogenes/tumor suppressors, MDM2, STAT1 and STAT2 were found to be up-regulated in NPC. The expression profile of growth factors/cytokines showed the up-regulation of many growth-enhancing factors such as EGR1, tumor-derived growth factor 1, platelet-derived growth factor A chain etc. as well as Th1-type cytokines e.g. interleukin-1beta and interferons. A smaller number of genes were down-regulated in nasopharyngeal cancer, such as those encoding ERK1, Raf, secreted apoptosis-related protein 1, CD27BP, transforming growth factor beta2, pre-B-cell-stimulating factor homologue etc.
The consistent tendency toward cell proliferation, the possibility of a stronger antiapoptotic force that operates on the normal apoptotic pathway, or the autocrine or paracrine growth factors may account for the development of NPC. Some genes are reported for the first time to have changed expression in nasopharyngeal carcinoma. The simple, quick, and high-throughput method of profiling gene expression by cDNA array hybridization provides us with a quick overview of key factors that may be involved in NPC, and may identify genes suitable for further study of carcinogenesis mechanism or targets for possible molecular diagnosis or therapy.
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ABSTRACT: Inflammasomes are cytoplasmic receptors that can recognize intracellular pathogens or danger signals and are critical for IL-1β production. Although several key components of inflammasome activation have been identified, there has not been a systematic analysis of the protein components found in the stimulated complex. In this study, we used the isobaric tags for relative and absolute quantification (iTRAQ) approach to systemically analyze the interactomes of the NLRP3, AIM2, and RIG-I inflammasomes in NPC cells treated with specific stimuli of these interactomes (H2O2, poly (dA:dT) and EBER, respectively). We identified a number of proteins that appeared to be involved in the interactomes and also could be precipitated with anti-ASC antibodies after stimulation. Among them, EB1 was an interacting component in all three interactomes. Silencing of EB1 expression by small interfering RNA inhibited the activation of the three inflammasomes, as indicated by reduced levels of IL-1β secretion. We confirmed that EB1 directly interacted with AIM2 and ASC in vitro and in vivo. Most importantly, fluorescence confocal microscopy showed that EB1 was required for formation of the speck-like particles that represent activation of the AIM2 inflammasome. In NPC tissues, IHC staining showed that EB1 expression was elevated and significantly correlated with AIM2 and ASC expression in NPC tumor cells. In sum, we profiled the interactome components of three inflammasomes and show for the first time that EB1 is crucial for the speck-like particle formation that represents activated inflammasomes.Molecular & Cellular Proteomics 08/2012; · 7.25 Impact Factor
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ABSTRACT: To identify the novel gene signatures and molecular markers of nasopharyngeal carcinoma (NPC) by integrated bioinformatics analysis of multiple gene expression profiling datasets. Seven published gene expression profiling studies and one of our unpublished works were reanalyzed to identify the common significantly dysregulated (CSD) genes in NPC. Overrepresentation analysis of cytogenetic bands, Gene Ontology (GO) categories, pathways were used to explore CSD genes functionally associated with carcinogenesis. The protein expressions of selected CSD genes were examined by immunohistochemistry on tissue microarrays, and the correlations of their expressions with clinical outcomes were evaluated. Using the criteria (genes reported deregulated in more than one study), a total of 962 genes were identified as the CSD genes in NPC. Four upregulated (BUB1B, CCND2, CENPF, and MAD2L1) and two downregulated (LTF and SLPI) genes were markedly reported in six studies. The enrichments of chromosome aberrations were 2q23, 2q31, 7p15, 12q15, 12q22, 18q11, and 18q12 in upregulated genes and 14q32 and 16q13 in downregulated genes. The activated GO categories and pathways related to proliferation, adhesion, invasion, and downregulated immune response had been functionally associated with NPC. SLPI significantly downregulated in nasopharyngeal adenocarcinoma. Furthermore, the high expression of BUB1B or CENPF was associated with poor overall survival of patients. It was first clearly identified the dysregulated expression of BUB1B and SLPI in NPC tissues. Further studies of the CSD genes as gene signatures and molecular markers of NPC might improve the understanding of the disease and identify new therapeutic targets.Cancer Epidemiology Biomarkers & Prevention 11/2011; 21(1):166-75. · 4.56 Impact Factor
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ABSTRACT: The phenotype of malignant epithelial cells in nasopharyngeal carcinomas (NPC) results from latent infection by the Epstein-Barr virus (EBV) combined to cell gene alterations, especially those affecting the p16/lnk 4 gene. At the site of the primary tumor, NPC are strongly infiltrated by non-malignant EBV-negative T-lymphocytes. There are experimental clues suggesting that these lymphocytes are involved in tumor development, for example by providing anti-apoptotic signals to malignant epithelial cells. The amazing geographic distribution of NPC is accounted for by the conjunction of several risk factors in endemic regions. These risk factors are related to the diffusion of one or several susceptibility genes, the probable existence of viral strains with high oncogenic potential and non-viral environmental factors, especially dietary factors. The perspectives of immunotherapy in NPC are still unclear since viral proteins detected in tumors are poorly immunogenic (EBNA1, LMP1). Targeted molecules designed to interfere with viral and cellular oncoprotein signals will probably have interesting applications for the treatment of NPC.Cancer/Radiothérapie 11/2001; 5. · 1.48 Impact Factor