• Title/Summary/Keyword: Microarray gene expression data

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Identification of Hub Genes in the Pathogenesis of Ischemic Stroke Based on Bioinformatics Analysis

  • Yang, Xitong;Yan, Shanquan;Wang, Pengyu;Wang, Guangming
    • Journal of Korean Neurosurgical Society
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    • v.65 no.5
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    • pp.697-709
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    • 2022
  • Objective : The present study aimed to identify the function of ischemic stroke (IS) patients' peripheral blood and its role in IS, explore the pathogenesis, and provide direction for clinical research progress by comprehensive bioinformatics analysis. Methods : Two datasets, including GSE58294 and GSE22255, were downloaded from Gene Expression Omnibus database. GEO2R was utilized to obtain differentially expressed genes (DEGs). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of DEGs were performed using the database annotation, visualization and integrated discovery database. The protein-protein interaction (PPI) network of DEGs was constructed by search tool of searching interactive gene and visualized by Cytoscape software, and then the Hub gene was identified by degree analysis. The microRNA (miRNA) and miRNA target genes closely related to the onset of stroke were obtained through the miRNA gene regulatory network. Results : In total, 36 DEGs, containing 27 up-regulated and nine down-regulated DEGs, were identified. GO functional analysis showed that these DEGs were involved in regulation of apoptotic process, cytoplasm, protein binding and other biological processes. KEGG enrichment analysis showed that these DEGs mediated signaling pathways, including human T-cell lymphotropic virus (HTLV)-I infection and microRNAs in cancer. The results of PPI network and cytohubba showed that there was a relationship between DEGs, and five hub genes related to stroke were obtained : SOCS3, KRAS, PTGS2, EGR1, and DUSP1. Combined with the visualization of DEG-miRNAs, hsa-mir-16-5p, hsa-mir-181a-5p and hsa-mir-124-3p were predicted to be the key miRNAs in stroke, and three miRNAs were related to hub gene. Conclusion : Thirty-six DEGs, five Hub genes, and three miRNA were obtained from bioinformatics analysis of IS microarray data, which might provide potential targets for diagnosis and treatment of IS.

A hybrid method to compose an optimal gene set for multi-class classification using mRMR and modified particle swarm optimization (mRMR과 수정된 입자군집화 방법을 이용한 다범주 분류를 위한 최적유전자집단 구성)

  • Lee, Sunho
    • The Korean Journal of Applied Statistics
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    • v.33 no.6
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    • pp.683-696
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    • 2020
  • The aim of this research is to find an optimal gene set that provides highly accurate multi-class classification with a minimum number of genes. A two-stage procedure is proposed: Based on minimum redundancy and maximum relevance (mRMR) framework, several statistics to rank differential expression genes and K-means clustering to reduce redundancy between genes are used for data filtering procedure. And a particle swarm optimization is modified to select a small subset of informative genes. Two well known multi-class microarray data sets, ALL and SRBCT, are analyzed to indicate the effectiveness of this hybrid method.

Comparison of Cytokine Gene Induction in RAW 264.7 Cells by Porphyromonas gingivalis and Escherichia coli Lipopolysaccharide

  • Lee, Young-Hwa;Jeong, So-Yeon;Na, Hee-Sam;Jeong, Sung-Hee;Park, Hae-Ryoun;Chung, Jin
    • International Journal of Oral Biology
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    • v.35 no.3
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    • pp.121-128
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    • 2010
  • Porphyromonas gingivalis lipopolysaccharide (Pg LPS) is an important virulence factor in chronic periodontitis. The aim of this study was to compare the expression of inflammatory cytokine genes in Escherichia coli LPS (Ec LPS) and Pg LPS-stimulated mouse macrophage RAW 264.7 cells. Cells were treated with Ec LPS and Pg LPS for 18 hours, and the cytokine gene expression profile was assessed using microarrays and confirmed by real-time PCR. Microarray analysis showed that both types of LPS induced a significant increase in the expression of IL-$17{\beta}$, IL-2, Ccl4, Cxcl2 and $TNF{\alpha}$ compared with the control. However, LT-b was up-regulated by Pg LPS but not by Ec LPS. Real-time PCR analysis of these genes showed similar results for LT-b, Ccl4, Cxcl2, and TNF-$\alpha$ but found that IL-$17{\beta}$ and IL-2 were upregulated by Pg LPS but not by Ec LPS. These data indicate that Pg LPS stimulates the transcription of IL-$17{\beta}$, IL-2, Ccl4, Cxcl2, LT-b, and $TNF{\alpha}$, all of which may be involved in the pathogenesis of chronic periodontitis.

Change of Insulin-like Growth Factor Gene Expression in Chinese Hamster Ovary Cells Cultured in Serum-free Media

  • Park, Hong-Woo;An, Sung-Kwan;Choe, Tae-Boo
    • Biotechnology and Bioprocess Engineering:BBE
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    • v.11 no.4
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    • pp.319-324
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    • 2006
  • Although the sera used in animal cell culture media provide the macromolecules, nutrients, hormones, and growth factors necessary to support cell growth, it could also be an obstacle to the production of recombinant proteins in animal cell culture systems used in many sectors of the biotechnology industry. For this reason, many research groups, including our laboratory, have been trying to develop serum-free media (SFM) or serum-supplemented media (SSM) for special or multi-purpose cell lines. The Chinese hamster ovary (CHO) cell, for example, is frequently used to produce proteins and is especially valuable in the large-scale production of pharmaceutically important proteins, yet information about its genome is lacking. Also, SFMs have only been evaluated by comparing growth patterns for cells grown in SFMs with those grown in SSM or by measuring the titer of the target protein obtained from cells grown in each type of medium. These are not reliable methods of obtaining the type of information needed to determine whether an SFM should be replaced with an SSM. We carried out a cDNA microarray analysis to evaluate MED-3, an SFM developed in our laboratory, as a CHO culture medium When CHO cells were cultured in MED-3 instead of an SSM, several genes associated with cell growth were down-regulated, although this change diminished over time. We found that the insulin-like growth factor (IGF) gene was representative of the proteins that were down-regulated in cells cultured in MED-3. When several key supplements - including insulin, transferrin, ethanolamine, and selenium - were removed from MED-3, the IGF expression was consistently down- regulated and cell growth decreased proportionately. Based on these results, we concluded that when an SFM is used as a culture medium, it is important to supplement it with substances that can help the cells maintain a high level of IGF expression. The data presented in this study, therefore, might provide useful information for the design and development of SFM or SSM, as well as for the design of genome-based studies of CHO cells to determine how they can be used optimally for protein production in pharmaceutical and biomedical research.

Characterization of a Drought-Tolerance Gene, BrDSR, in Chinese Cabbage (배추의 건조 저항성 유전자, BrDSR의 기능 검정)

  • Yu, Jae-Gyeong;Lee, Gi-Ho;Park, Young-Doo
    • Horticultural Science & Technology
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    • v.34 no.1
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    • pp.102-111
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    • 2016
  • The goal of this study was to characterize the BrDSR (Drought Stress Resistance in B. rapa) gene and to identify the expression network of drought-inducible genes in Chinese cabbage under drought stress. Agrobacterium-mediated transformation was conducted using a B. rapa inbred line ('CT001') and the pSL100 vector containing the BrDSR full length CDS (438 bp open reading frame). Four transgenic plants were selected by PCR and the expression level of BrDSR was approximately 1.9-3.4-fold greater than that in the wild-type control under drought stress. Phenotypic characteristics showed that BrDSR over-expressing plants were resistant to drought stress and showed normal growth habit. To construct a co-expression network of drought-responsive genes, B. rapa 135K cDNA microarray data was analyzed to identify genes associated with BrDSR. BrDSR was directly linked to DARK INDUCIBLE 2 (DIN2, AT3G60140) and AUTOPHAGY 8H (ATG8H, AT3G06420) previously reported to be leaf senescence and autophagy-related genes in plants. Taken together, the results of this study indicated that BrDSR plays a significant role in enhancement of tolerance to drought conditions.

Circular RNA hsa_circ_0075828 promotes bladder cancer cell proliferation through activation of CREB1

  • Zhuang, Chengle;Huang, Xinbo;Yu, Jing;Gui, Yaoting
    • BMB Reports
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    • v.53 no.2
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    • pp.82-87
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    • 2020
  • Circular RNAs (circRNAs), one kind of non-coding RNA, have been reported as critical regulators for modulating gene expression in cancer. In this study, microarray analysis was used to screen circRNA expression profiles of bladder cancer (BC) 5637 cells, T24 cells and normal control SV-HUC-1 cells. The data from the microarray showed that hsa_circ_0075828 (named circCASC15) was most highly expressed in 5637 and T24 cells. circCASC15 was highly expressed in BC tissues and cells. Overexpression of circCASC15 was closely associated with BC tumor stage and promoted cell proliferation significantly in vitro and in vivo. Mechanistically, circCASC15 could act as miR-1224-5p sponge to activate the expression of CREB1 to promote cell proliferation in BC. In short, circCASC15 promotes cell proliferation in BC, which might be a new molecular target for BC diagnosis and therapy.

Differentially Expressed Genes by Inhibition of C-terminal Src Kinase by siRNA in Human Vascular Smooth Muscle Cells and Their Association with Blood Pressure

  • Hong, Kyung-Won;Shin, Young-Bin;Kim, Koan-Hoi;Oh, Berm-Seok
    • Genomics & Informatics
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    • v.9 no.3
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    • pp.102-113
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    • 2011
  • C-terminal SRC kinase (CSK) is a ubiquitously expressed, cytosolic enzyme that phosphorylates and inactivates several SRC family protein tyrosine kinases. Recent genomewide association studies have implicated CSK in the regulation of blood pressure. The current study aim is to determine the blood pressure association of the genes regulated by CSK down-regulation. The CSK mRNA expression was downregulated in vascular smooth muscle cells using small interfering RNA (siRNA). CSK mRNA levels fell by 90% in cells that were treated with CSK siRNA; the RNA from these cells was examined by microarray using the Illumina HumanRef-8 v3 platform, which comprises 24,526 reference mRNA probes. On treatment with CSK siRNA, 19 genes were downregulated by more than 2-fold and 13 genes were upregulated by more than 2-fold. Three (CANX, SLC30A7, and HMOX1) of them revealed more than 3 fold differential expression. Interestingly, the HMOX1 SNPs were associated with diastolic blood pressure in the 7551 Koreans using Korea Association REsource data, and the result was supported by the other reports that HMOX1 linked to blood vessel maintenance. Among the remaining 29 differentially expressed genes, seven (SSBP1, CDH2, YWHAE, ME2, PFTK1, G3BP2, and TUFT1) revealed association with both systolic and diastolic blood pressures. The CDH2 gene was linked to blood pressures. Conclusively, we identified 32 differentially expressed genes which were regulated by CSK reduction, and two (HOMX1 and CDH2) of them might influence the blood pressure regulation through CSK pathway.

Variable Selection in Normal Mixture Model Based Clustering under Heteroscedasticity (이분산 상황 하에서 정규혼합모형 기반 군집분석의 변수선택)

  • Kim, Seung-Gu
    • The Korean Journal of Applied Statistics
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    • v.24 no.6
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    • pp.1213-1224
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    • 2011
  • In high dimensionality where the number of variables are excessively larger than observations, it is required to remove the noninformative variables to cluster observations. Most model-based approaches for variable selection have been considered under the assumption of homoscedasticity and their models are mainly estimated by a penalized likelihood method. In this paper, a different approach is proposed to remove the noninformative variables effectively and to cluster based on the modified normal mixture model simultaneously. The validity of the model was provided and an EM algorithm was derived to estimate the parameters. Simulation studies and an experiment using real microarray dataset showed the effectiveness of the proposed method.

High-concentration Epigallocatechin Gallate Treatment Causes Endoplasmic Reticulum Stress-mediated Cell Death in HepG2 Cells

  • Ahn, Joon-Ik;Jeong, Kyoung-Ji;Ko, Moon-Jeong;Shin, Hee-Jung;Chung, Hye-Joo;Jeong, Ho-Sang
    • Genomics & Informatics
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    • v.7 no.2
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    • pp.97-106
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    • 2009
  • Epigallocatechin gallate (EGCG), a well-known antioxidant molecule, has been reported to cause hepatotoxicity when used in excess. However, the mechanism underlying EGCG-induced hepatotoxicity is still unclear. To better understand the mode of action of EGCG-induced hepatotoxicity, we examined the effect of EGCG on human hepatic gene expression in HepG2 cells using microarrays. Analyses of microarray data revealed more than 1300 differentially expressed genes with a variety of biological processes. Upregulated genes showed a primary involvement with protein-related biological processes, such as protein synthesis, protein modification, and protein trafficking, while downregulated genes demonstrated a strong association with lipid transport. Genes involved in cellular stress responses were highly upregulated by EGCG treatment, in particular genes involved in endoplasmic reticulum (ER) stress, such as GADD153, GADD34, and ATF3. In addition, changes in genes responsible for cholesterol synthesis and lipid transport were also observed, which explains the high accumulation of EGCG-induced lipids. We also identified other regulatory genes that might aid in clarifying the molecular mechanism underlying EGCG-induced hepatotoxicity.

Anti-tumor activities of Panax quinquefolius saponins and potential biomarkers in prostate cancer

  • He, Shan;Lyu, Fangqiao;Lou, Lixia;Liu, Lu;Li, Songlin;Jakowitsch, Johannes;Ma, Yan
    • Journal of Ginseng Research
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    • v.45 no.2
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    • pp.273-286
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    • 2021
  • Background: Prostate carcinoma is the second most common cancer among men worldwide. Developing new therapeutic approaches and diagnostic biomarkers for prostate cancer (PC) is a significant need. The Chinese herbal medicine Panax quinquefolius saponins (PQS) have been reported to show anti-tumor effects. We hypothesized that PQS exhibits anti-cancer activity in human PC cells and we aimed to search for novel biomarkers allowing early diagnosis of PC. Methods: We used the human PC cell line DU145 and the prostate epithelial cell line PNT2 to perform cell viability assays, flow cytometric analysis of the cell cycle, and FACS-based apoptosis assays. Microarray-based gene expression analysis was used to display specific gene expression patterns and to search for novel biomarkers. Western blot and quantitative real-time PCR were performed to demonstrate the expression levels of multiple cancer-related genes. Results: Our data showed that PQS inhibited the viability of DU145 cells and induced cell cycle arrest at the G1 phase. A significant decrease in DU145 cell invasion and migration were observed after 24 h treatment by PQS. PQS up-regulated the expression levels of p21, p53, TMEM79, ACOXL, ETV5, and SPINT1 while it down-regulated the expression levels of bcl2, STAT3, FANCD2, DRD2, and TMPRSS2. Conclusion: PQS promoted cells apoptosis and inhibited the proliferation of DU145 cells, which suggests that PQS may be effective for treating PC. TMEM79 and ACOXL were expressed significantly higher in PNT2 than in DU145 cells and could be novel biomarker candidates for PC diagnosis.