• Asian Pacific Journal of Cancer Prevention
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• v.13 no.8
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• pp.3681-3685
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• 2012

Background: In breast cancer, estrogen receptors have been demonstrated to interact with transcription factors to regulate target gene expression. However, high-throughput identification of the transcription regulation relationship between transcription factors and their target genes in response to estradiol is still in its infancy. Purpose: Thus, the objective of our study was to interpret the transcription regulation network of MCF7 breast cancer cells exposed to estradiol. Methods: In this work, GSE11352 microarray data were used to identify differentially expressed genes (DEGs). Results: Our results showed that the MYB (v-myb myeloblastosis viral oncogene homolog [avian]), PGR (progesterone receptor), and MYC (v-myc myelocytomatosis viral oncogene homolog [avian]) were hub nodes in our transcriptome network, which may interact with ER and, in turn, regulate target gene expression. MYB can up-regulate MCM3 (minichromosome maintenance 3) and MCM7 expression; PGR can suppress BCL2 (B-cell lymphoma 2) expression; MYC can inhibit TGFB2 (transforming growth factor, beta 2) expression. These genes are associated with breast cancer progression via cell cycling and the $TGF{\beta}$ signaling pathway. Conclusion: Analysis of transcriptional regulation may provide a better understanding of molecular mechanisms and clues to potential therapeutic targets in the treatment of breast cancer.

• BMB Reports
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• v.55 no.9
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• pp.417-428
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• 2022

Herbal medicine, a multi-component treatment, has been extensively practiced for treating various symptoms and diseases. However, its molecular mechanism of action on the human body is unknown, which impedes the development and application of herbal medicine. To address this, recent studies are increasingly adopting systems pharmacology, which interprets pharmacological effects of drugs from consequences of the interaction networks that drugs might have. Most conventional network-based approaches collect associations of herb-compound, compound-target, and target-disease from individual databases, respectively, and construct an integrated network of herb-compound-target-disease to study the complex mechanisms underlying herbal treatment. More recently, rapid advances in high-throughput omics technology have led numerous studies to exploring gene expression profiles induced by herbal treatments to elicit information on direct associations between herbs and genes at the genome-wide scale. In this review, we summarize key databases and computational methods utilized in systems pharmacology for studying herbal medicine. We also highlight recent studies that identify modes of action or novel indications of herbal medicine by harnessing drug-induced transcriptome data.

• Biotechnology and Bioprocess Engineering:BBE
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• v.10 no.5
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• pp.385-399
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• 2005

The phenotypic response of a cell results from a well orchestrated web of complex interactions which propagate from the genetic architecture through the metabolic flux network. To rationally design cell factories which carry out specific functional objectives by controlling this hierarchical system is a challenge. Transcriptome analysis, the most mature high-throughput measurement technology, has been readily applied In strain improvement programs in an attempt to Identify genes involved in expressing a given phenotype. Unfortunately, while differentially expressed genes may provide targets for metabolic engineering, phenotypic responses are often not directly linked to transcriptional patterns, This limits the application of genome-wide transcriptional analysis for the design of cell factories. However, improved tools for integrating transcriptional data with other high-throughput measurements and known biological interactions are emerging. These tools hold significant promise for providing the framework to comprehensively dissect the regulatory mechanisms that identify the cellular control mechanisms and lead to more effective strategies to rewire the cellular control elements for metabolic engineering.

• BMB Reports
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• v.54 no.9
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• pp.464-469
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• 2021

Cardiomyocyte differentiation occurs through complex and finely regulated processes including cardiac lineage commitment and maturation from pluripotent stem cells (PSCs). To gain some insight into the genome-wide characteristics of cardiac lineage commitment, we performed transcriptome analysis on both mouse embryonic stem cells (mESCs) and human induced PSCs (hiPSCs) at specific stages of cardiomyocyte differentiation. Specifically, the gene expression profiles and the protein-protein interaction networks of the mESC-derived platelet-derived growth factor receptor-alpha (PDGFRα)⁺ cardiac lineage-committed cells (CLCs) and hiPSC-derived kinase insert domain receptor (KDR)⁺ and PDGFRα⁺ cardiac progenitor cells (CPCs) at cardiac lineage commitment were compared with those of mesodermal cells and differentiated cardiomyocytes. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses revealed that the genes significantly upregulated at cardiac lineage commitment were associated with responses to organic substances and external stimuli, extracellular and myocardial contractile components, receptor binding, gated channel activity, PI3K-AKT signaling, and cardiac hypertrophy and dilation pathways. Protein-protein interaction network analysis revealed that the expression levels of genes that regulate cardiac maturation, heart contraction, and calcium handling showed a consistent increase during cardiac differentiation; however, the expression levels of genes that regulate cell differentiation and multicellular organism development decreased at the cardiac maturation stage following lineage commitment. Additionally, we identified for the first time the protein-protein interaction network connecting cardiac development, the immune system, and metabolism during cardiac lineage commitment in both mESC-derived PDGFRα⁺ CLCs and hiPSC-derived KDR⁺PDGFRα⁺ CPCs. These findings shed light on the regulation of cardiac lineage commitment and the pathogenesis of cardiometabolic diseases.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.3
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• pp.767-773
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• 2012

The esophageal squamous cell carcinoma (ESCC) is an aggressive tumor with a poor prognosis. Understanding molecular changes in ESCC should improve identification of risk factors with different molecular subtypes and provide potential targets for early detection and therapy. Our study aimed to obtain a molecular signature of ESCC through the regulation network based on differentially expressed genes (DEGs). We used the GSE23400 series to identify potential genes related to ESCC. Based on bioinformatics we constructed a regulation network. From the results, we could establish that many transcription factors and pathways closely related with ESCC were linked by our method. STAT1 also arose as a hub node in our transcriptome network, along with some transcription factors like CCNB1, TAP1, RARG and IFITM1 proven to be related with ESCC by previous studies. In conclusion, our regulation network provided information on important genes which might be useful in investigating the complex interacting mechanisms underlying the disease.

• Childhood Kidney Diseases
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• v.15 no.1
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• pp.38-48
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• 2011

Purpose: Focal segmental glomerulosclerosis (FSGS) is the most common glomerulopathy causing pediatric renal failure. Since specific treatment targeting the etiology and pathophysiology of primary FSGS is yet elusive, the authors explored the pathophysiology of FSGS by transcriptome analysis of the disease using an animal model. Methods: FGS/kist strain, a mouse model of primary FSGS, and RFM/kist strain, as control and the parent strain of FGS/kist, were used. Kidney tissues were harvested and isolated renal cortex was used to extract mRNA, which was run on AB 1700 mouse microarray chip after reverse transcription to get the transcriptome profile. Results: Sixty two genes were differentially expressed in FGS/kist kidney tissue compared to the control. Those genes were related to cell cycle/cell death, immune reaction, and lipid metabolism/vasculopathy, and the key molecules of their networks were TNF, IL-6/4, IFN${\gamma}$, TP53, and PPAR${\gamma}$. Conclusion: This study confirmed that renal cell death, immune system activation with subsequent fibrosis, and lipid metabolism-related early vasculopathy were involved in the pathophysiology of FSGS. In addition, the relevance of methodology used in this study, namely transcriptome profiling, and Korean animal model of FGS/kist was validated. Further study would reveal novel pathophysiology of FSGS for new therapeutic targets.

• 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.

• Proceedings of the Korean Society of Crop Science Conference
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• 2022.10a
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• pp.207-207
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• 2022

Eating and cooking quality (ECQ) is one of the most complex quantitative traits in rice. The understanding of genetic regulation of transcript expression levels attributing to phenotypic variation in ECQ traits is limited. We integrated whole-genome resequencing, transcriptome, and phenotypic variation data from 84 Japonica accessions to build a transcriptome-wide association study (TWAS) based regulatory network. All ECQ traits showed a large phenotypic variation and significant phenotypic correlations among the traits. TWAS analysis identified a total of 285 transcripts significantly associated with six ECQ traits. Genome-wide mapping of ECQ-associated transcripts revealed 66,905 quantitative expression traits (eQTLs), including 21,747 local eQTLs, and 45,158 trans-eQTLs, regulating the expression of 43 genes. The starch synthesis-related genes (SSRGs), starch synthase IV-1 (SSIV-1), starch branching enzyme 1 (SBE1), granule-bound starch synthase 2 (GBSS2), and ADP-glucose pyrophosphorylase small subunit 2a (OsAGPS2a) were found to have eQTLs regulating the expression of ECQ associated transcripts. Further, in co-expression analysis, 130 genes produced at least one network with 22 master regulators. In addition, we developed CRISPR/Cas9-edited glbl mutant lines that confirmed the role of alpha-globulin (glbl) in starch synthesis to validate the co-expression analysis. This study provided novel insights into the genetic regulation of ECQ traits, and transcripts associated with these traits were discovered that could be used in further rice breeding.

• Parasites, Hosts and Diseases
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• v.58 no.5
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• pp.513-525
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• 2020

Clonorchis sinensis is a food-borne trematode that infects more than 15 million people. The liver fluke causes clonorchiasis and chronical cholangitis, and promotes cholangiocarcinoma. The underlying molecular pathogenesis occurring in the bile duct by the infection is little known. In this study, transcriptome profile in the bile ducts infected with C. sinensis were analyzed using microarray methods. Differentially expressed genes (DEGs) were 1,563 and 1,457 at 2 and 4 weeks after infection. Majority of the DEGs were temporally dysregulated at 2 weeks, but 519 DEGs showed monotonically changing expression patterns that formed seven distinct expression profiles. Protein-protein interaction (PPI) analysis of the DEG products revealed 5 sub-networks and 10 key hub proteins while weighted co-expression network analysis (WGCNA)-derived gene-gene interaction exhibited 16 co-expression modules and 13 key hub genes. The DEGs were significantly enriched in 16 Kyoto Encyclopedia of Genes and Genomes pathways, which were related to original systems, cellular process, environmental information processing, and human diseases. This study uncovered a global picture of gene expression profiles in the bile ducts infected with C. sinensis, and provided a set of potent predictive biomarkers for early diagnosis of clonorchiasis.

• ALGAE
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• v.39 no.1
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• pp.17-30
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• 2024

Red macroalga Pyropia yezoensis is a high valuable cultivated marine crop. Its acclimation to cold stress is especially important for long cultivation period across winter in coasts of warm temperate zone in East Asia. In this study, the response of P. yezoensis thalli to low temperature was analyzed on physiology and transcriptome level, to explore its acclimation mechanism to cold stress. The results showed that the practical photosynthesis activity (indicated by Φ_PSII and qP) was depressed and pigment allophycocyanin content was decreased during the cold stress of 48 h. However, the F_v/F_m and non-photochemical quenching increased significantly after 24 h, and the average growth rate of thalli also rebounded from 24 to 48 h, indicating a certain extent of acclimation to cold stress. On transcriptionally, the low temperature promoted the expression of differentially expressed genes (DEGs) related to carbohydrate metabolism and energy metabolism, while genes related to photosynthetic system were depressed. The increased expression of DEGs involved in ribosomal biogenesis and lipid metabolism which could accelerate protein synthesis and enhance the degree of fatty acid unsaturation, might help P. yezoensis thallus cells to cope with cold stress. Further co-expression network analysis revealed differential expression trends along with stress time, and corresponding hub genes play important roles in the systemic acquired acclimation to cold stress. This study provides basic mechanisms of P. yezoensis acclimation to cold temperature and may aid in exploration of functional genes for genetic breeding of economic macroalgae.