CRSD: a comprehensive web server for composite regulatory signature discovery

Liu, Chun-Chi; Lin, Chia-Ho; Chen, Wen-Shyen E.; Chen, Hsuan‐Yu; Chang, Pei-Chun; Chen, Jeremy J.W.

doi:10.1093/nar/gkl279

Cited by 35 publications

(34 citation statements)

References 30 publications

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“…Genes with multiple roles were included in more than one category. Our in-house data mining tool 8 (35) revealed that the Ras-MAPK, Rac1 signaling, and regulation of actin cytoskeleton pathways were suppressed by tanshinone I (Fig. 6).…”

Section: Identification Of the Genes Responding Totanshinone I By Micmentioning

confidence: 99%

Anticancer effects of tanshinone I in human non-small cell lung cancer

Lee¹,

Sher

Chen

et al. 2008

Molecular Cancer Therapeutics

116

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Tanshinones are the major bioactive compounds of Salvia miltiorrhiza Bunge (Danshen) roots, which are used in many therapeutic remedies in Chinese traditional medicine. We investigated the anticancer effects of tanshinones on the highly invasive human lung adenocarcinoma cell line, CL1-5. Tanshinone I significantly inhibited migration, invasion, and gelatinase activity in macrophage-conditioned medium-stimulated CL1-5 cells in vitro and also reduced the tumorigenesis and metastasis in CL1-5-bearing severe combined immunodeficient mice. Unlike tanshinone IIA, which induces cell apoptosis, tanshinone I did not have direct cytotoxicity. Real-time quantitative PCR, luciferase reporter assay, and electrophoretic mobility shift assay revealed that tanshinone I reduces the transcriptional activity of interleukin-8, the angiogenic factor involved in cancer metastasis, by attenuating the DNA-binding activity of activator protein-1 and nuclear factor-KB in conditioned medium-stimulated CL1-5 cells. Microarray and pathway analysis of tumorrelated genes identified the differentially expressed genes responding to tanshinone I, which may be associated with the Ras-mitogen-activated protein kinase and Rac1 signaling pathways. These results suggest that tanshinone I exhibits anticancer effects both in vitro and in vivo and that these effects are mediated at least partly through the interleukin-8, Ras-mitogen-activated protein kinase, and Rac1 signaling pathways. Although tanshinone I has a remarkable anticancer action, its potential anticoagulant effect should be noted and evaluated.

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Section: Identification Of the Genes Responding Totanshinone I By Micmentioning

confidence: 99%

Anticancer effects of tanshinone I in human non-small cell lung cancer

Lee¹,

Sher

Chen

et al. 2008

Molecular Cancer Therapeutics

116

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“…GSE20318), followed by the analysis with our in-house pathway analysis tool (29) as well as a commercial software, GeneGo (http://www.genego.com/metacore). These pathway analyses had identified 4 EMT-related pathways in the top 10 pathways that were significantly affected by YWHAZ.…”

Section: Ywhaz Induces a Neuron-like Morphologic Change And Emtmentioning

confidence: 99%

A Novel Function of YWHAZ/β-Catenin Axis in Promoting Epithelial–Mesenchymal Transition and Lung Cancer Metastasis

Chen

Chuang

Yang

et al. 2012

Molecular Cancer Research

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YWHAZ, also known as 14-3-3zeta, has been reportedly elevated in many human tumors, including non-small cell lung carcinoma (NSCLC) but little is known about its specific contribution to lung cancer malignancy. Through a combined array-based comparative genomic hybridization and expression microarray analysis, we identified YWHAZ as a potential metastasis enhancer in lung cancer. Ectopic expression of YWHAZ on low invasive cancer cells showed enhanced cell invasion, migration in vitro, and both the tumorigenic and metastatic potentials in vivo. Gene array analysis has indicated these changes associated with an elevation of pathways relevant to epithelial-mesenchymal transition (EMT), with an increase of cell protrusions and branchings. Conversely, knockdown of YWHAZ levels with siRNA or short hairpin RNA (shRNA) in invasive cancer cells led to a reversal of EMT. We observed that high levels of YWHAZ protein are capable of activating b-catenin-mediated transcription by facilitating the accumulation of b-catenin in cytosol and nucleus. Coimmunoprecipitation assays showed a decrease of ubiquitinated b-catenin in presence of the interaction between YWHAZ and b-catenin. This interaction resulted in disassociating b-catenin from the binding of b-TrCP leading to increase b-catenin stability. Using enforced expression of dominant-negative and -positive b-catenin mutants, we confirmed that S552 phosphorylation of b-catenin increases the b-catenin/YWHAZ complex formation, which is important in promoting cell invasiveness and the suppression of ubiquitnated b-catenin. This is the first demonstration showing YWHAZ through its complex with b-catenin in mediating lung cancer malignancy and b-catenin protein stability. Mol Cancer Res; 10(10); 1319-31. Ó2012 AACR. IntroductionLung cancer is a malignant tumor with a high incidence and mortality rate (1). Non-small cell lung cancer (NSCLC) represents 80% of all lung cancers and has an overall 5-year survival rate of 10% to 15% (2). Metastasis is the main cause of treatment failure and cancer-related deaths. In carcinomas, metastasis is a multiple step process, the first of which is invasion (3). Cancer cells acquire their invasive capacity

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“…Recently, there has been an increased interest in methods that allow a systems view of the studied process, a view that observes not only the components of a system but also their emergent properties. This includes methods that uncover the functional themes that characterize gene expression profiles (15, 16) as well as methods that use advanced computational algorithms for the integration of multiple levels of information (17)(18)(19) and identification of regulatory modules in complex tissue and in disease (20).In this study we create a global map of asthma using publicly available gene expression datasets from multiple sources and tools that allow integration of multiple levels of information, such as functional annotations and protein interactions (Figure 1). In addition to providing a comprehensive description of this map, we present examples of novel observations.…”

mentioning

confidence: 99%

mentioning

confidence: 99%

A Functional and Regulatory Map of Asthma

Novershtern

Barnett-Itzhaki²,

Manor³

et al. 2008

Am J Respir Cell Mol Biol

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The prevalence and morbidity of asthma, a chronic inflammatory airway disease, is increasing. Animal models provide a meaningful but limited view of the mechanisms of asthma in humans. A systemslevel view of asthma that integrates multiple levels of molecular and functional information is needed. For this, we compiled a gene expression compendium from five publicly available mouse microarray datasets and a gene knowledge base of 4,305 gene annotation sets. Using this collection we generated a high-level map of the functional themes that characterize animal models of asthma, dominated by innate and adaptive immune response. We used Module Networks analysis to identify co-regulated gene modules. The resulting modules reflect four distinct responses to treatment, including early response, general induction, repression, and IL-13-dependent response. One module with a persistent induction in response to treatment is mainly composed of genes with suggested roles in asthma, suggesting a similar role for other module members. Analysis of IL-13-dependent response using protein interaction networks highlights a role for TGF-b1 as a key regulator of asthma. Our analysis demonstrates the discovery potential of systems-level approaches and provides a framework for applying such approaches to asthma.Keywords: house dust mite; IL-13; ovalbumin; systems biology; TGF-b Asthma is a chronic lung disease characterized by airway inflammation, hyperresponsiveness, remodeling, and obstruction (1). The lung phenotype in asthma is believed to be determined by the interaction of the environment with the patient's genetic background (2). This interaction leads to a dramatic change in the airway microenvironment that includes activation of inflammatory pathways, recruitment of immune cells that are not usually present in the airway, and a dramatic change in the phenotype of airway resident cells. While individual changes in many of these factors may generate components of the asthmatic phenotype, it is the converging effects of these pathways on recruited and altered cells that determine the patient's disease.The advent of high-throughput technologies for gene and protein profiling has greatly improved our ability to characterize the behavior of genes and proteins in health and disease. Using animal models of allergic airway disease, investigators applied DNA microarrays to identify potential regulators of asthmatic airway inflammation such as C5 (3), ARG1 (4), ADAM8 (5), SPRR2 (6) as well as to explore the pathways activated by IL13 and STAT6 during the development of allergen-induced lung inflammation (7-9). Transcriptional analysis of the response to IL-13, allergen challenge, syncytial virus infection, and corticosteroids in epithelial cells identified multiple and rarely overlapping genes (10-14). While many of these studies used elegant experimental approaches to dissect pathways and to identify and validate potential novel key regulatory molecules, the majority of their insights were obtained using statistical methods that select...

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CRSD: a comprehensive web server for composite regulatory signature discovery

Cited by 35 publications

References 30 publications

Anticancer effects of tanshinone I in human non-small cell lung cancer

Anticancer effects of tanshinone I in human non-small cell lung cancer

A Novel Function of YWHAZ/β-Catenin Axis in Promoting Epithelial–Mesenchymal Transition and Lung Cancer Metastasis

A Functional and Regulatory Map of Asthma

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