• Title/Summary/Keyword: Biomarker gene

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Odorant G protein-coupled receptors as potential therapeutic targets for adult diffuse gliomas: a systematic analysis and review

  • Cho, Hee Jin;Koo, JaeHyung
    • BMB Reports
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    • v.54 no.12
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    • pp.601-607
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    • 2021
  • Odorant receptors (ORs) account for about 60% of all human G protein-coupled receptors (GPCRs). OR expression outside of the nose has functions distinct from odor perception, and may contribute to the pathogenesis of disorders including brain diseases and cancers. Glioma is the most common adult malignant brain tumor and requires novel therapeutic strategies to improve clinical outcomes. Here, we outlined the expression of brain ORs and investigated OR expression levels in glioma. Although most ORs were not ubiquitously expressed in gliomas, a subset of ORs displayed glioma subtype-specific expression. Moreover, through systematic survival analysis on OR genes, OR51E1 (mouse Olfr558) was identified as a potential biomarker of unfavorable overall survival, and OR2C1 (mouse Olfr15) was identified as a potential biomarker of favorable overall survival in isocitrate dehydrogenase (IDH) wild-type glioma. In addition to transcriptomic analysis, mutational profiles revealed that somatic mutations in OR genes were detected in > 60% of glioma samples. OR5D18 (mouse Olfr1155) was the most frequently mutated OR gene, and OR5AR1 (mouse Olfr1019) showed IDH wild-type-specific mutation. Based on this systematic analysis and review of the genomic and transcriptomic profiles of ORs in glioma, we suggest that ORs are potential biomarkers and therapeutic targets for glioma.

The Chromatin Accessibility Landscape of Nonalcoholic Fatty Liver Disease Progression

  • Kang, Byeonggeun;Kang, Byunghee;Roh, Tae-Young;Seong, Rho Hyun;Kim, Won
    • Molecules and Cells
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    • v.45 no.5
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    • pp.343-352
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    • 2022
  • The advent of the assay for transposase-accessible chromatin using sequencing (ATAC-seq) has shown great potential as a leading method for analyzing the genome-wide profiling of chromatin accessibility. A comprehensive reference to the ATAC-seq dataset for disease progression is important for understanding the regulatory specificity caused by genetic or epigenetic changes. In this study, we present a genome-wide chromatin accessibility profile of 44 liver samples spanning the full histological spectrum of nonalcoholic fatty liver disease (NAFLD). We analyzed the ATAC-seq signal enrichment, fragment size distribution, and correlation coefficients according to the histological severity of NAFLD (healthy control vs steatosis vs fibrotic nonalcoholic steatohepatitis), demonstrating the high quality of the dataset. Consequently, 112,303 merged regions (genomic regions containing one or multiple overlapping peak regions) were identified. Additionally, we found differentially accessible regions (DARs) and performed transcription factor binding motif enrichment analysis and de novo motif analysis to determine new biomarker candidates. These data revealed the gene-regulatory interactions and noncoding factors that can affect NAFLD progression. In summary, our study provides a valuable resource for the human epigenome by applying an advanced approach to facilitate diagnosis and treatment by understanding the non-coding genome of NAFLD.

Effects of Lactobacillus reuteri MG5346 on Receptor Activator of Nuclear Factor-Kappa B Ligand (RANKL)-Induced Osteoclastogenesis and Ligature-Induced Experimental Periodontitis Rats

  • Yu-Jin Jeong;Jae-In Jung;YongGyeong Kim;Chang-Ho Kang;Jee-Young Imm
    • Food Science of Animal Resources
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    • v.43 no.1
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    • pp.157-169
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    • 2023
  • Effects of culture supernatants of Lactobacillus reuteri MG5346 (CS-MG5346) on receptor activator of nuclear factor-kappa B ligand (RANKL)-induced osteoclastogenesis were examined. CS-MG5346 treatment up to 400 ㎍/mL significantly reduced tartrate-resistant acid-phosphatase (TRAP) activity, the phenotype biomarker of osteoclast, without affecting cell viability. CS-MG5346 inhibited the expression of osteoclast specific transcriptional factors (c-fos and nuclear factor-activated T cells c1) and their target genes (TRAP, cathepsin, and matrix metallo-proteinase-9) in a dose-dependent manner (p<0.05). The administration of L. reuteri MG5346 (2×108 CFU/day) for 8 wks significantly improved furcation involvement, but no difference was observed in alveolar bone loss in ligature-induced experimental periodontitis rats. The elevated RANKL/osteoprotegerin ratio, the biomarker of periodontitis, was significantly lowered in the gingival tissue by administration of L. reuteri MG5346 (p<0.05). L. reuteri MG5346 showed excellent stability in simulated stomach and intestinal fluids and did not have antibiotic resistance. Based on the results, L. reuteri MG5346 has the potential to be a promising probiotic strain for oral health.

Cloning and Expression of Phytochelatin Synthase 1 Gene from Rhizophora stylosa Exposed to Cadmium and Copper (카드뮴과 구리에 노출된 Rhizophora stylosa 의 phytochelatin synthase 1 유전자 클로닝 및 발현)

  • Lee, Gunsup;Hwang, Jinik;Park, Mirye;Chung, Youngjae;Lee, Taek-Kyun
    • Journal of the Korea Academia-Industrial cooperation Society
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    • v.14 no.6
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    • pp.3114-3119
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    • 2013
  • The mangrove ecosystems have the capacity to act as a sink of heavy metals entering aquatic ecosystems. Despite their potential exposure to metal contaminated sediments, mangroves appear to be highly tolerant to heavy metals. In this study, we cloned metal tolerance gene from mangrove plant. Using CTAB method, RNA were isolated from leaves and root tissue of Rhizophora stylosa habitated at Weno island in Micronesia Chuuk lagoon using CTAB method and phytochelatin synthase 1 (PCS1) gene was cloned using gene specific primers. Expression of PCS1 gene was increased 1.91 fold and 2.72 fold in mangrove propagules exposed to 100 ppb Cd and 10 ppb Cu, respectively. These results indicate that expression of PCS1 gene are promising tools for health assessment of mangrove ecosystem.

Comparative co-expression analysis of RNA-Seq transcriptome revealing key genes, miRNA and transcription factor in distinct metabolic pathways in diabetic nerve, eye, and kidney disease

  • Asmy, Veerankutty Subaida Shafna;Natarajan, Jeyakumar
    • Genomics & Informatics
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    • v.20 no.3
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    • pp.26.1-26.19
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    • 2022
  • Diabetes and its related complications are associated with long term damage and failure of various organ systems. The microvascular complications of diabetes considered in this study are diabetic retinopathy, diabetic neuropathy, and diabetic nephropathy. The aim is to identify the weighted co-expressed and differentially expressed genes (DEGs), major pathways, and their miRNA, transcription factors (TFs) and drugs interacting in all the three conditions. The primary goal is to identify vital DEGs in all the three conditions. The overlapped five genes (AKT1, NFKB1, MAPK3, PDPK1, and TNF) from the DEGs and the co-expressed genes were defined as key genes, which differentially expressed in all the three cases. Then the protein-protein interaction network and gene set linkage analysis (GSLA) of key genes was performed. GSLA, gene ontology, and pathway enrichment analysis of the key genes elucidates nine major pathways in diabetes. Subsequently, we constructed the miRNA-gene and transcription factor-gene regulatory network of the five gene of interest in the nine major pathways were studied. hsa-mir-34a-5p, a major miRNA that interacted with all the five genes. RELA, FOXO3, PDX1, and SREBF1 were the TFs interacting with the major five gene of interest. Finally, drug-gene interaction network elucidates five potential drugs to treat the genes of interest. This research reveals biomarker genes, miRNA, TFs, and therapeutic drugs in the key signaling pathways, which may help us, understand the processes of all three secondary microvascular problems and aid in disease detection and management.

Classification of Genes Based on Age-Related Differential Expression in Breast Cancer

  • Lee, Gunhee;Lee, Minho
    • Genomics & Informatics
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    • v.15 no.4
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    • pp.156-161
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    • 2017
  • Transcriptome analysis has been widely used to make biomarker panels to diagnose cancers. In breast cancer, the age of the patient has been known to be associated with clinical features. As clinical transcriptome data have accumulated significantly, we classified all human genes based on age-specific differential expression between normal and breast cancer cells using public data. We retrieved the values for gene expression levels in breast cancer and matched normal cells from The Cancer Genome Atlas. We divided genes into two classes by paired t test without considering age in the first classification. We carried out a secondary classification of genes for each class into eight groups, based on the patterns of the p-values, which were calculated for each of the three age groups we defined. Through this two-step classification, gene expression was eventually grouped into 16 classes. We showed that this classification method could be applied to establish a more accurate prediction model to diagnose breast cancer by comparing the performance of prediction models with different combinations of genes. We expect that our scheme of classification could be used for other types of cancer data.

Genetic and Epigenetic Biomarkers on the Personalized Nutrition

  • An Sung-Whan
    • Proceedings of the Korean Society of Food Science and Nutrition Conference
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    • 2004.11a
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    • pp.271-274
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    • 2004
  • Nutritional genomics is a new field of study of how nutrition interacts with an individual's genome or individual responds to individual diets. Systematic approach of nutritional genomics will likely provide important clues about responders and non-responders. The current interest in personalizing health stems from the breakthroughs emerging in integrative technologies of genomics and epigenomics and the identification of genetic and epigentic diversity in individual's genetic make-up that are associated with variations in many aspects of health, including diet-related diseases. Microarray is a powerful screen system that is being also currently employed in nutritional research. Monitoring of gene expression at genome level is now possible with this technology, which allows the simultaneous assessment of the transcription of tens of thousands of genes and of their relative expression of pathological cells such tumor cells compared with that of normal cells. Epigenetic events such as DNA methylation can result in change of gene expression without involving changes in gene sequence. Recent developed technology of DNAarray-based methylation assay will facilitate wide study of epigenetic process in nutrigenomics. Some of the areas that would benefitfrom these technologies include identifying molecular targets (Biomarkers) for the risk and benefit assessment. These characterized biomarkers can reflect expose, response, and susceptibility to foods and their components. Furthermore the identified new biomarker perhaps can be utilized as a indicator of delivery system fur optimizing health.

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Differentially Expressed Genes in Marine Medaka Fish (Oryzias javanicus) Exposed to Cadmium

  • Woo, Seon-Ock;Son, Sung-Hee;Park, Hong-Seog;Vulpe, Chris D.;Ryu, Jae-Chun;Yum, Seung-Shic
    • Molecular & Cellular Toxicology
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    • v.4 no.4
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    • pp.293-299
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    • 2008
  • To screen the differentially expressed genes in cadmuim-exposed marine medaka fish (Oryzias javanicus), a candidate marine test fish for ecological toxicity, the differential display polymerase chain reaction (DD-PCR) was carried out, since the genome-wide gene expression data are not available in this fish species yet. A total of 35 clones were isolated from cadmium-exposed fish and their nucleotide sequences were analyzed. The differentially expressed gene candidates were categorized to response to stimulus (3); ion binding (3); DNA binding (1); protein binding (6); carbohydrate binding (1); metabolic process (4); biological regulation (3); cellular process (2); protein synthesis (2); catalytic activity (2); sense of sight (1); immune (1); neurohormone (1); signaling activity (1); electron carrier activity (1) and others (3). For real-time quantitative RT-PCR, we selected catalase, glucose-6-phosphate dehydrogenase, heat shock protein 70, and metallothionein and confirmed that cadmium exposure enhanced induction of these four genes.

Serum exosomal miR-192 serves as a potential detective biomarker for early pregnancy screening in sows

  • Ruonan Gao;Qingchun Li;Meiyu Qiu;Su Xie;Xiaomei Sun;Tao Huang
    • Animal Bioscience
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    • v.36 no.9
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    • pp.1336-1349
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    • 2023
  • Objective: The study was conducted to screen differentially expressed miRNAs in sows at early pregnancy by high-throughput sequencing and explore its mechanism of action on embryo implantation. Methods: The blood serum of pregnant and non-pregnant Landrace×Yorkshire sows were collected 14 days after artificial insemination, and exosomal miRNAs were purified for high throughput miRNA sequencing. The expression patterns of 10 differentially expressed (DE) miRNAs were validated by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The qRT-PCR quantified the abundance of serum exosomal miR-192 in pregnant and control sows, and the diagnostic power was assessed by receiver operating characteristic (ROC) analysis. The target genes of DE miRNAs were predicted with bioinformatics software, and the functional and pathway enrichment analysis was performed on gene ontology and the Kyoto encyclopedia of genes and genomes terms. Furthermore, a luciferase reporter system was used to identify the target relation between miR-192 and integrin alpha 4 (ITGA4), a gene influencing embryo implantation in pigs. Finally, the expression levels of miRNAs and the target gene ITGA4 were analyzed by qRT-PCR, and western blot, with the proliferation of BeWo cells detected by cell counting kit-8 (CCK-8). Results: A total of 221 known miRNAs were detected in the libraries of the pregnant and non-pregnant sows, of which 55 were up-regulated and 67 were down-regulated in the pregnant individuals compared with the non-pregnant controls. From these, the expression patterns of 10 DE miRNAs were validated. The qRT-PCR analysis further confirmed a significantly higher expression of miR-192 in the serum exosomes extracted from pregnant sows, when compared to controls. The ROC analysis revealed that miR-192 provided excellent diagnostic accuracy for pregnancy (area under the ROC curve [AUC]=0.843; p>0.001). The dual-luciferase reporter assay indicated that miR-192 directly targeted ITGA4. The protein expression of ITGA4 was reduced in cells that overexpressed miR-192. Overexpression of miR-192 resulted in the decreased proliferation of BeWo cells and regulated the expression of cell cycle-related genes. Conclusion: Serum exosomal miR-192 could serve as a potential biomarker for early pregnancy in pigs. miR-192 targeted ITGA4 gene directly, and miR-192 can regulate cellular proliferation.

Comparison of Hsp90 and CYP1A Expression Patterns by Water Temperature Stress in Atlantic Salmon (Salmo salar) (대서양 연어(Salmo salar)의 수온 스트레스에 의한 Hsp90 및 CYP1A 발현 양상 비교)

  • Kang, Han Seung;Song, Jae-Hee;Kang, Hee Woong
    • Journal of Marine Life Science
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    • v.3 no.2
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    • pp.51-58
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    • 2018
  • Variations in water temperature are known to affect almost every part of fish physiology. The rise in water temperature due to climate change can physically damage fish. This study was conducted to evaluate the health status of the Atlantic salmon (Salmo salar) at high water temperature (20℃) than the optimum water temperature (15℃). Liver tissue exerts important metabolic functions in thermal adaptation. Therefore, liver tissue was used in this study. The evaluation method is to develop the biomarker gene using NGS RNAseq analysis and to examine the expression pattern using RT-qPCR analysis. The NGS RNAseq analysis revealed 1,366 differentially expressed genes, among which 880 genes were increase expressed and 486 genes were decrease expressed. The biomarker genes are such as heat shock protein 90 alpha (Hsp90α), heat shock protein 90 beta (Hsp90β) and cytochrome P450 1A (CYP1A). The selected genes are sensitive to changes in water temperature through NGS RNAseq analysis. Expression patterns of these genes through RT-qPCR were similar to those of NGS RNAseq analysis. The results of this study can be applied to other fish species and it is considered to be useful industrially.