• Title/Summary/Keyword: gene signature

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Analysis of opposing histone modifications H3K4me3 and H3K27me3 reveals candidate diagnostic biomarkers for TNBC and gene set prediction combination

  • Park, Hyoung-Min;Kim, HuiSu;Lee, Kang-Hoon;Cho, Je-Yoel
    • BMB Reports
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    • v.53 no.5
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    • pp.266-271
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    • 2020
  • Breast cancer encompasses a major portion of human cancers and must be carefully monitored for appropriate diagnoses and treatments. Among the many types of breast cancers, triple negative breast cancer (TNBC) has the worst prognosis and the least cases reported. To gain a better understanding and a more decisive precursor for TNBC, two major histone modifications, an activating modification H3K4me3 and a repressive modification H3K27me3, were analyzed using data from normal breast cell lines against TNBC cell lines. The combination of these two histone markers on the gene promoter regions showed a great correlation with gene expression. A list of signature genes was defined as active (highly enriched H3K4me3), including NOVA1, NAT8L, and MMP16, and repressive genes (highly enriched H3K27me3), IRX2 and ADRB2, according to the distribution of these histone modifications on the promoter regions. To further enhance the investigation, potential candidates were also compared with other types of breast cancer to identify signs specific to TNBC. RNA-seq data was implemented to confirm and verify gene regulation governed by the histone modifications. Combinations of the biomarkers based on H3K4me3 and H3K27me3 showed the diagnostic value AUC 93.28% with P-value of 1.16e-226. The results of this study suggest that histone modification analysis of opposing histone modifications may be valuable toward developing biomarkers and targets for TNBC.

Toxicogenomics Study on Carbon Tetrachloride-induced Hepatotoxicity in Mice

  • Jeong, Sun-Young;Lim, Jung-Sun;Hwang, Ji-Yoon;Park, Han-Jin;Cho, Jae-Woo;Song, Chang-Woo;Kim, Yang-Seok;Lee, Wan-Seon;Moon, Jin-Hee;Han, Sang-Seop;Yoon, Seok-Joo
    • Molecular & Cellular Toxicology
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    • v.1 no.4
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    • pp.275-280
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    • 2005
  • Carbon tetrachloride ($CCl_4$) is well known hepatotoxicant. Its overdose cause severe centrilobular hepatic necrosis in human and experimental animals. We administered $CCl_{4}$ at low (0.2 mL/kg p.o.) and high (2 mL/kg p.o.) doses to mice. Mice were sacrificed at 24 h after administration. We evaluated liver toxicity by serum AST and ALT level and by microscopic observation. Using cDNA chip, we conducted gene expression analysis in liver. Mean serum activities of the hepatocellular leakage enzymes, ALT and AST, were significantly increased compare to control, respectively, in the low and high dose groups. H&E evaluation of stained liver sections revealed $CCl_{4}-related$ histopathological findings in mice. Moderate centrilobular hepatocellular necrosis was present in all $CCl_{4}$ treated mice. We found that gene expression pattern was very similar between low and high dose group. However, some stress related genes were differently expressed. These results could be a molecular signature for the degree of liver injury. Our data suggest that the degree of severity could be figure out by gene expression profiling.

Quantitative analysis of gene expression pattern in aspergillus nidulans mycelia by sequencing of 3-directed cDNA clones

  • Park. Yoon-Dong;Lee, Dong-Whan;Lee, Seog-Jae;Kim, Jong-Hwa;Chae, Keon-Sang
    • Journal of Microbiology
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    • v.34 no.1
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    • pp.25-29
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    • 1996
  • Since sequencing of randomly selected cDNA clones has been known to be a powerful approach to obtain information on gene expression pattern in specific cells or tissues, we have analyzed a 3'-directed cDNA library of vegetative mycelia of A. nidulans by single-pass sequencing of hundreds of randomly selected clones. Sequencing of 292 cDNA clones yielded 209 gene signatures (GSs) probably representing highly or lesser expressed genes in the vegetative mycelia. Among the 209 GSs, 25 (79 cDNA clones) appeared more than once and 184 only once. One GS appeared at a highest frequency of 6 times, 2 GSs5 times, 4 GSs 4 times, a GSs 3 times and 16 GSs twice. About 6.6% GSs comprizing of 13 GSs showed alternative polyadenylation. Among 23 redundant GSs, three were common in both mycelia and sexual organs, and 22 were probably mycelia-specific. Out of 209 GSs, 36 were identified in GenBank showing of 70% or greater similaritis. Only six GSs were for A. nidulans genes, and 13 GSs were of DNA or genes encoding cytoplasmic or organellar proteins. This pattern is similar to those in the human HepG2 cell line and in human colonic mucosa, although very few genes for nuclear proteins and for protein synthesis were in A. nidulans.

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Genetic Diversity and Population Structure Analyses of SSIV-2 Gene in Rice

  • Thant Zin Maung;Yong-Jin Park
    • Proceedings of the Korean Society of Crop Science Conference
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    • 2022.10a
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    • pp.212-212
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    • 2022
  • Soluble starch synthase (SS) IV-2 is one of the starch synthase gene family members and responsible for starch chain elongation interacting with other rice eating and cooking quality controlling genes (e.g., AGPlar and PUL). SSIV-2 is mainly expressed in leaves, especially at grain-filling stage and its alleles can significantly affect rice quality. Here, we investigated the genetic diversity and population structure analyses of SSIV-2 gene by using 374 rice accessions. This rice set was grouped into 320 cultivated bred (subsequently classified into temperate japonica, indica, tropical japonica, aus, aromatic and admixture) and 54 wild rice. Haplotyping of cultivated rice accessions provided a total of 7 haplotypes, and only three haplotypes are functional indicating four substituted SNPs in two exons of chromosome 5: T/A and G/T in exon 4, and C/G and G/A in exon 13. Including the wild, a highest diverse group (0.0041), nucleotide diversity analysis showed temperate japonica (0.0001) had a lowest diversity value indicating the origin information of this gene evolution. Higher and positive Tajima5s D value of indica (1.9755) indicate a selective signature under balancing selection while temperate japonica (-0.9018) was in lowest Tajima's D value due to a recent selective sweep by positive selection. We found the most diverse genetic components of the wild in PCA but shared in some portion with other cultivated groups. Fixation index (FST-values) and phylogenetic analysis indicate a closer relationship of the wild with indica (FST=0.256) than to its association to both of temperate japonica (FST=0.589). Structure analysis shows a clear separation of cultivated subpopulations at every K value, but genetic components were admixed within the wild illustrating the same genetic background with japonica and indica in some proportion.

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Genomic identification and spatial expression analysis of Rab-5C-like gene identified from rock bream(Oplegnathus fasciatus)

  • Mothishri, M.S.;Umasuthan, Navaneethaiyer;Thulasitha, William Shanthakumar;Whang, Ilson;Lee, Jehee
    • Journal of fish pathology
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    • v.28 no.2
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    • pp.99-107
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    • 2015
  • Despite its economic importance as an aquaculture species, the molecular and genetic information regarding physiologically important elements in rock bream (Oplegnathus fasciatus) is not completely understood. Rab proteins play a vital role in cellular mechanisms and immunity as one of the key regulators of membrane trafficking. In this investigation, a Rab gene, named as RbRab-5C-like, was identified from Oplegnathus fasciatus. RbRab-5C-like protein exhibited high homology with Rab proteins of other species and possessed signature characteristics of Rab proteins with four conserved cysteine residues. Phylogenetic analysis showed that RbRab-5C-like clustered with other fish counterparts. The RbRab-5C-like genomic sequence possesses six exons and five introns. Transcriptional analysis revealed that RbRab-5C-like was ubiquitously expressed in all examined tissues with the highest expression occurring in the liver. While the structural and homologic characteristics of RbRab-5C-like suggest a strong conservation of this element in different species, its mRNA distribution implies a wide range of biological significance in rock bream.

MiRNA Molecular Profiles in Human Medical Conditions: Connecting Lung Cancer and Lung Development Phenomena

  • Aghanoori, Mohamad-Reza;Mirzaei, Behnaz;Tavallaei, Mahmood
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.22
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    • pp.9557-9565
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    • 2014
  • MiRNAs are endogenous, single stranded ~22-nucleotide non-coding RNAs (ncRNAs) which are transcribed by RNA polymerase II and mediate negative post-transcriptional gene regulation through binding to 3'untranslated regions (UTR), possibly open reading frames (ORFs) or 5'UTRs of target mRNAs. MiRNAs are involved in the normal physiology of eukaryotic cells, so dysregulation may be associated with diseases like cancer, and neurodegenerative, heart and other disorders. Among all cancers, lung cancer, with high incidence and mortality worldwide, is classified into two main groups: non-small cell lung cancer and small cell lung cancer. Recent promising studies suggest that gene expression profiles and miRNA signatures could be a useful step in a noninvasive, low-cost and repeatable screening process of lung cancer. Similarly, every stage of lung development during fetal life is associated with specific miRNAs. Since lung development and lung cancer phenomena share the same physiological, biological and molecular processes like cell proliferation, development and shared mRNA or expression regulation pathways, and according to data adopted from various studies, they may have partially shared miRNA signature. Thus, focusing on lung cancer in relation to lung development in miRNA studies might provide clues for lung cancer diagnosis and prognosis.

Molecular Comparison of Mating Type Loci and Adjacent Chromosomal Regions from Self-fertile and Self-sterile Cochliobolus Species

  • Yun, Sung-Hwan;B. Gillian Turgeon;Turgeon
    • The Plant Pathology Journal
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    • v.15 no.3
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    • pp.131-136
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    • 1999
  • In fungi known as ascomycetes, ability to mate is controlled by a single mating type (MAT) locus with two dissimilar sequences called idiomorphs carrying genes encoding transcription factors that are unrelated to each other. Fungi requiring strains with different MAT genes to complete the sexual process are heterothallic (self-sterile); species in which as single strain is able to undergo sexual reproduction are homothallic (self-fertile). Previous analysis of sequences from several heterothallic and homothallic species of the ascomycete genus Cochliobolus showed that homothallics evolve from heterothallics and that each known Cochliobolus homothallic species arose independently, from a different heterothallic ancestral species. Here we report detailed comparative analyses of MAT sequences ad their flanking regions, and show that: (1) The level of MAT gene similarity is not correlated with reproductive life style; (2) MAT proteins from all Cochliobolus species are conserved within the transcription factor signature sequences; they are not conserved in the carboxy terminal half of MAT-1, or third of MAT-2, except in those from very closely related species; (3) A gene (ORF1) of unknown function, consistently found on the MAT flank, is more conserved than are the MAT genes themselves; (4) The intergenic sequences diverge sharply among species.

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Characterization of PUL Haplotypes and Its Evolutionary Analyses in Korean Rice Accessions

  • Thant Zin Maung;Yong-Jin Park
    • Proceedings of the Korean Society of Crop Science Conference
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    • 2022.10a
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    • pp.217-217
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    • 2022
  • Pullulanase (PUL), a debranching enzyme, has been utilized in hydrolyzing the a-1,6 glucosidic linkages in starch, amylopectin, pullulan, as well as related oligosaccharides. It has also been indicated that PUL is a novel indicator of inherent RS (Resistant Starch) formation in rice. In this study, we performed haplotype analysis on 320 bred rice accessions, and additional 54 wild accessions were added to study genetic diversity along with other population-based analyses of the PUL gene. Through these investigations, we summarized a total of 10 functional (non-synonymous) SNPs from 7 different exons on chromosome 4. There were 10 haplotypes, of which only six haplotypes were functional, implicating different subpopulations. Diversity reduction was noticed in temperate japonica (0.0005) compared to the highest one (aus, 0.0154), illustrating their higher genetic differentiation by FST-value (0.926). The highest Tajima^ D value was observed in indica (3.6613), indicating PUL gene domestication signature under balancing selection, while the lowest Tajima's D value was found in temperate japonica (-2.2191) which might have undergone under positive selection and purified due to the excess of rare alleles. PCA, population structure, and phylogenetic analyses provide information on the genetic relatedness between and or among the cultivated subpopulations and the wild based on PUL genomic region.

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Predicting Hosts through Molecular Analysis of Ichneumonid Guts

  • Kang, Gyu Won;Choi, Jin Kyung;Lee, Jong Wook;Suk, Ho Young
    • Animal Systematics, Evolution and Diversity
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    • v.38 no.4
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    • pp.199-204
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    • 2022
  • Ichneumonidae are well-known parasitoids that attack the larvae or pupae of other insects. This study analyzed whether the abdominal DNA of two ichneumonid wasps, Pimpla disparis and Theronia atalantae gestator, showed the signature of the host species, Ivela auripes. Observations confirmed that these two ichneumonids were the representative parasitoid species growing in the larvae of I. auripes. In addition, sequence analysis showed that the mitochondrial cytochrome oxidase I gene of the host was amplified completely from the DNA extracted from the gut tissues of the ichneumonids. Even after 96 h of adulthood, the host's DNA traces did not disappear and were amplified in many individuals. These results suggest a constructive first step for establishing of a host information bank for ichneumonids in the future.

Cloning, Characterization and Expression Analysis of Interleukin-10 from the Zebrafish (Danio rerion)

  • Zhang, Dian-Chang;Shao, Yan-Qing;Huang, Yan-Qin;Jiang, Shi-Gui
    • BMB Reports
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    • v.38 no.5
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    • pp.571-576
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    • 2005
  • Cytokines are proteins produced by many different cells of the immune system and play a significant role in initiating and regulating the inflammatory process. In this research, an important cytokine, interleukin-10 (IL-10) gene, has been identified and characterized from zebrafish (Danio rerio) genome database. Zebrafish IL-10 is located within a 2690 bp fragment and contains five exons and four introns, sharing the same organization with mammalian IL-10 genes. An open reading frame of 543 bp was found to encode a putative 180 amino acid protein with a signal peptide of 22 amino acids, which shares 29.7-80.9% homology with amino acid sequences of other known IL-10. The signature motif of IL-10 is also conserved in zebrafish IL-10. The predicted transcript was finally confirmed by sequencing of cDNA clones. Multi-tissue reverse transcriptase PCR (RT-PCR) was performed to examine the tissue distribution and expression regulation of this gene in seven organs of normal and lipopolysaccharide (LPS) stimulation zebrafish. The results demonstrated that this gene was expressed slightly in normal kidney, gill and gut, no expression was detected in other four tissues. The expression was clearly upregulated after LPS stimulation. Using the ideal zebrafish model, further study of IL-10 characterization and function may provide insight on the understanding of the innate immune system.