• Asian Pacific Journal of Cancer Prevention
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• v.15 no.24
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• pp.10847-10853
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• 2015

Background: Lapatinib, a dual tyrosine kinase inhibitor that interrupts the epidermal growth factor receptor (EGFR) and HER2/neu pathways, has been indicated to have significant efficacy in treating HER2-positive breast cancer. However, acquired drug resistance has become a very serious clinical problem that hampers the use of this agent. In this study, we aimed to screen small molecule drugs that might reverse lapatinib-resistance of breast cancer by exploring differentially expressed genes (DEGs) via a bioinformatics method. Materials and Methods: We downloaded the gene expression profile of BT474-J4 (acquired lapatinib-resistant) and BT474 (lapatinib-sensitive) cell lines from the Gene Expression Omnibus (GEO) database and selected differentially expressed genes (DEGs) using dChip software. Then, gene ontology and pathway enrichment analyses were performed with the DAVID database. Finally, a connectivity map was utilized for predicting potential chemicals that reverse lapatinib-resistance. Results: A total of 1, 657 DEGs were obtained. These DEGs were enriched in 10 pathways, including cell cycling, regulation of actin cytoskeleton and focal adhesion associate examples. In addition, several small molecules were screened as the potential therapeutic agents capable of overcoming lapatinib-resistance. Conclusions: The results of our analysis provided a novel strategy for investigating the mechanism of lapatinib-resistance and identifying potential small molecule drugs for breast cancer treatment.

• Journal of Ginseng Research
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• v.47 no.5
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• pp.645-653
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• 2023

Background: Changes to work-life balance has increased the incidence of cervical cancer among younger people. A minor ginseng saponin known as ginsenoside Rk1 can inhibit the growth and survival of human cancer cells; however, whether ginsenoside Rk1 inhibits HeLa cell proliferation is unknown. Methods and results: Ginsenoside Rk1 blocked HeLa cells in the G0/G1 phase in a dose-dependent manner and inhibited cell division and proliferation. Ginsenoside Rk1 markedly also activated the apoptotic signaling pathway via caspase 3, PARP, and caspase 6. In addition, ginsenoside Rk1 increased LC3B protein expression, indicating the promotion of the autophagy signaling pathway. Protein processing in the endoplasmic reticulum signaling pathway was downregulated in Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses, consistent with teal-time quantitative PCR and western blotting that showed YOD1, HSPA4L, DNAJC3, and HSP90AA1 expression levels were dramatically decreased in HeLa cells treated with ginsenoside Rk1, with YOD1 was the most significantly inhibited by ginsenoside Rk1 treatment. Conclusion: These findings indicate that the toxicity of ginsenoside Rk1 in HeLa cells can be explained by the inhibition of protein synthesis in the endoplasmic reticulum and enhanced apoptosis, with YOD1 acting as a potential target for cervical cancer treatment.

• Journal of Plant Biotechnology
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• v.50
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• pp.127-136
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• 2023

Water scarcity decreases the rate of photosynthesis and, consequently, the yield of banana plants (Musa spp). In this study, transcriptome analysis was performed to identify photosynthesis-related genes in banana plants and determine their expression profiles under water stress conditions. Banana plantlets were in vitro cultured on Murashige and Skoog agar medium with and without 10% polyethylene glycol and marked as BP10 and BK. Chlorophyll contents in the plant shoots were determined spectrophotometrically. Two cDNA libraries generated from BK and BP10 plantlets, respectively, were used as the reference for transcriptome data. Gene ontology (GO) enrichment analysis was performed using the Database for Annotation, Visualization, and Integrated Discovery (DAVID) and visualized using the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway prediction. Morphological observations indicated that water deficiency caused chlorosis and reduced the shoot chlorophyll content of banana plantlets. GO enrichment identified 52 photosynthesis-related genes that were affected by water stress. KEGG visualization revealed the pathways related to the 52 photosynthesisr-elated genes and their allocations in four GO terms. Four, 12, 15, and 21 genes were related to chlorophyll biosynthesis, the Calvin cycle, the photosynthetic electron transfer chain, and the light-harvesting complex, respectively. Differentially expressed gene (DEG) analysis using DESeq revealed that 45 genes were down-regulated, whereas seven genes were up-regulated. Four of the down-regulated genes were responsible for chlorophyll biosynthesis and appeared to cause the decrease in the banana leaf chlorophyll content. Among the annotated DEGs, MaPNDO, MaPSAL, and MaFEDA were selected and validated using quantitative real-time PCR.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.12
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• pp.7221-7227
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• 2013

Background: Fascin, an actin-bundling protein forming actin bundles including filopodia and stress fibers, is overexpressed in multiple human epithelial cancers including esophageal squamous cell carcinoma (ESCC). Previously we conducted a microarray experiment to analyze fascin knockdown by RNAi in ESCC. Method: In this study, the differentially expressed genes from mRNA expression profilomg of fascin knockdown were analyzed by multiple bioinformatics methods for a comprehensive understanding of the role of fascin. Results: Gene Ontology enrichment found terms associated with cytoskeleton organization, including cell adhesion, actin filament binding and actin cytoskeleton, which might be related to fascin function. Except GO categories, the differentially expressed genes were annotated by 45 functional categories from the Functional Annotation Chart of DAVID. Subpathway analysis showed thirty-nine pathways were disturbed by the differentially expressed genes, providing more detailed information than traditional pathway enrichment analysis. Two subpathways derivated from regulation of the actin cytoskeleton were shown. Promoter analysis results indicated distinguishing sequence patterns and transcription factors in response to the co-expression of downregulated or upregulated differentially expressed genes. MNB1A, c-ETS, GATA2 and Prrx2 potentially regulate the transcription of the downregulated gene set, while Arnt-Ahr, ZNF42, Ubx and TCF11-MafG might co-regulate the upregulated genes. Conclusions: This multiple bioinformatic analysis helps provide a comprehensive understanding of the roles of fascin after its knockdown in ESCC.

• 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.

• Animal Bioscience
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• v.37 no.3
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• pp.451-460
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• 2024

Objective: The objective is to identify genomic regions and candidate genes associated with age to 105 kg (AGE), average daily gain (ADG), backfat thickness (BF), and eye muscle area (EMA) in Yorkshire pig. Methods: This study used a total of 104,380 records and 11,854 single nucleotide polymorphism (SNP) data obtained from Illumina porcine 60K chip. The estimated genomic breeding values (GEBVs) and SNP effects were estimated by single-step genomic best linear unbiased prediction (ssGBLUP). Results: The heritabilities of AGE, ADG, BF, and EMA were 0.50, 0.49, 0.49, and 0.23, respectively. We identified significant SNP markers surpassing the Bonferroni correction threshold (1.68×10^-6), with a total of 9 markers associated with both AGE and ADG, and 4 markers associated with BF and EMA. Genome-wide association study (GWAS) analyses revealed notable chromosomal regions linked to AGE and ADG on Sus scrofa chromosome (SSC) 1, 6, 8, and 16; BF on SSC 2, 5, and 8; and EMA on SSC 1. Additionally, we observed strong linkage disequilibrium on SSC 1. Finally, we performed enrichment analyses using gene ontology and Kyoto encyclopedia of genes and genomes (KEGG), which revealed significant enrichments in eight biological processes, one cellular component, one molecular function, and one KEGG pathway. Conclusion: The identified SNP markers for productive traits are expected to provide valuable information for genetic improvement as an understanding of their expression.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.3
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• pp.1731-1735
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• 2013

Objective: We aimed to identify key genes, pathways and function modules in the development of diffuse large B-cell lymphoma (DLBCL) with microarray data and interaction network analysis. Methods: Microarray data sets for 7 DLBCL samples and 7 normal controls was downloaded from the Gene Expression Omnibus (GEO) database and differentially expressed genes (DEGs) were identified with Student's t-test. KEGG functional enrichment analysis was performed to uncover their biological functions. Three global networks were established for immune system, signaling molecules and interactions and cancer genes. The DEGs were compared with the networks to observe their distributions and determine important key genes, pathways and modules. Results: A total of 945 DEGs were obtained, 272 up-regulated and 673 down-regulated. KEGG analysis revealed that two groups of pathways were significantly enriched: immune function and signaling molecules and interactions. Following interaction network analysis further confirmed the association of DEGs in immune system, signaling molecules and interactions and cancer genes. Conclusions: Our study could systemically characterize gene expression changes in DLBCL with microarray technology. A range of key genes, pathways and function modules were revealed. Utility in diagnosis and treatment may be expected with further focused research.

• Genomics & Informatics
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• v.10 no.4
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• pp.244-248
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• 2012

Oxidative stress, which results in an excessive product of reactive oxygen species (ROS), is one of the fundamental mechanisms of the development of hypertension. In the vascular system, ROS have physical and pathophysiological roles in vascular remodeling and endothelial dysfunction. In this study, ROS-hypertension-related genes were collected by the biological literature-mining tools, such as SciMiner and gene2pubmed, in order to identify the genes that would cause hypertension through ROS. Further, single nucleotide polymorphisms (SNPs) located within these gene regions were examined statistically for their association with hypertension in 6,419 Korean individuals, and pathway enrichment analysis using the associated genes was performed. The 2,945 SNPs of 237 ROS-hypertension genes were analyzed, and 68 genes were significantly associated with hypertension (p < 0.05). The most significant SNP was rs2889611 within MAPK8 (p = $2.70{\times}10^{-5}$; odds ratio, 0.82; confidence interval, 0.75 to 0.90). This study demonstrates that a text mining approach combined with association analysis may be useful to identify the candidate genes that cause hypertension through ROS or oxidative stress.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.4
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• pp.1361-1365
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• 2015

Background: We aimed to discover potential gene biomarkers for gastric cancer (GC) diagnosis. Materials and Methods: Genechips of 10 GC tissues and 10 gastric mucosa (GM, para-carcinoma tissue, normal control) tissues were generated using an exon array of Affymetrix containing 30,000 genes. The differentially expressed genes (DEGs) between GC tissues and normal control were identified by the Limma package and analyzed by hierarchical clustering analysis. Gene ontology (GO) and pathway enrichment analyses were performed for investigating the functions of DEGs. Receiver operating characteristics (ROC) analysis was performed to measure the effects of biomarker candidates for diagnosis of GC. Results: Totals of 896 up-regulated and 60 down-regulated DEGs were identified to be differentially expressed between GC samples and normal control. Hierarchical clustering analysis showed that DEGs were highly differentially expressed and most DEGs were up-regulated. The most significantly enriched GO-BP term was revealed to be mitotic cell cycle and the most significantly enriched pathway was cell cycle. The intersection analysis showed that most significant DEGs were cyclin B1 (CCNB1) and cyclin B2 (CCNB2). The sensitivities and specificities of CCNB1 and CCNB2 were both high (p<0.0001). Areas under the ROC curve for CCNB1 and CCNB2 were both greater than 0.9 (p<0.0001). Conclusions: CCNB1 and CCNB2, which were involved in cell cycle, played significant roles in the progression and development of GC and these genes may be potential biomarkers for diagnosis and prognosis of GC.

• The Journal of Korean Medicine
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• v.45 no.1
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• pp.114-125
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• 2024

Objectives: Network pharmacology is an analysis method that explores drug-centered efficacy and mechanism by constructing a compound-target-disease network based on system biology, and is attracting attention as a methodology for studying herbal medicine that has the characteristics for multi-compound therapeutics. Thus, we investigated the potential functions and pathways of Myrrha on Allergic Rhinitis (AR) via network pharmacology analysis and molecular docking. Methods: Using public databases and PubChem database, compounds of Myrrha and their target genes were collected. The putative target genes of Myrrha and known target genes of AR were compared and found the correlation. Then, the network was constructed using STRING database, and functional enrichment analysis was conducted based on the Gene Ontology (GO) Biological process and Kyoto Encyclopedia of Genes and Genomes (KEGG) Pathways. Binding-Docking stimulation was performed using CB-Dock. Results: The result showed that total 3 compounds and 55 related genes were gathered from Myrrha. 33 genes were interacted with AR gene set, suggesting that the effects of Myrrha are closely related to AR. Target genes of Myrrha are considerably associated with various pathways including 'Fc epsilon RI signaling pathway' and 'JAK-STAT signaling pathway'. As a result of blinding docking, AKT1, which is involved in both mechanisms, had high binding energies for abietic acid and dehydroabietic acid, which are components of Myrrha. Conclusion: Through a network pharmacological method, Myrrha was predicted to have high relevance with AR by regulating AKT1. This study could be used as a basis for studying therapeutic effects of Myrrha on AR.