• Asian Pacific Journal of Cancer Prevention
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• v.15 no.1
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• pp.123-127
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• 2014

A recent study summarized several published genome-wide association studies (GWASs) of cancer and reported two pleiotropic loci at 6p21.1 and 7p15.3 contributing to multiple cancers including lung cancer, noncardia gastric cancer (NCGC), and esophageal squamous-cell carcinoma (ESCC) in Han Chinese. However, it is not known whether such genetic variants have similar effects on the risk of gynecologic cancers, such as ovarian cancer. Hence, we explored associations between genetic variants in 6p21.1 and 7p15.3 and ovarian cancer risk in Han Chinese women. We performed an independent case-control study by genotyping the two loci (rs2494938 A > G at 6p21.1 and rs2285947 A > G at 7p15.3) in a total of 377 ovarian cancer cases and 1,034 cancer-free controls using TaqMan allelic discrimination assay. We found that rs2285947 at 7p15.3 was significantly associated with risk of ovarian cancer with per allele odds ratio (OR) of 1.33 [95% confidence interval (CI): 1.08-1.64, P=0.008]. However, no significant association was observed between rs2494938 and ovarian cancer risk. Our results showed that rs2285947 at 7p15.3 may also contribute to the development of ovarian cancer in Han Chinese women, further suggesting pleiotropy of 7p15.3 in multiple cancers.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.1
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• pp.85-91
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• 2014

Background: Genome-wide association studies (GWAS) have identified various genetic susceptibility loci for breast cancer based mainly on European-ancestry populations. Differing linkage disequilibrium patterns exist between European and Asian populations. Methods: Ten SNPs (rs2075555 in COL1A1, rs12652447 in FBXL17, rs10941679 in 5p12/MRPS30, rs11878583 in ZNF577, rs7166081 in SMAD3, rs16917302 in ZNF365, rs311499 in 20q13.3, rs1045485 in CASP8, rs12964873 in CDH1 and rs8170 in 19p13.1) were here genotyped in 1009 Chinese females (487 patients with breast cancer and 522 control subjects) using the Sequenom MassARRAY iPLEX platform. Association analysis based on unconditional logistic regression was carried out to determine the odds ratio (OR) and 95% confidence interval (95% CI) for each SNP. Stratification analyses were carried out based on the estrogen receptor (ER) and progesterone receptor (PR) status. Results: Among the 10 SNPs, rs10941679 showed significant association with breast cancer when differences between the case and control groups in this Han Chinese population were compared (30.09% GG, 45.4% GA and 23.7% AA; P = 0.012). Four SNPs (rs311499, rs1045485, rs12964873 and rs8170) showed no polymorphisms in our study. The remaining five SNPs showed no association with breast cancer in the present population. Immunohistochemical tests showed that rs2075555 was associated with ER status; the AA genotype showed greater association with ER negative than ER positive (OR = 0.54, 95% CI, 0.29-0.99; P = 0.046). AA of rs7166081 was also associated with ER status, but showed a greater association with ER positive than negative (OR = 1.59, 95% CI = 1.04-2.44; P = 0.031). However, no significant associations were found among the SNPs and PR status. Conclusion: In this study using a Han Chinese population, rs10941679 was the only SNP associated with breast cancer risk, indicating a difference between European and Chinese populations in susceptibility loci. Therefore, confirmation studies are necessary before utilization of these loci in Chinese.

• Proceedings of the Korean Institute of Information and Commucation Sciences Conference
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• 2018.05a
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• pp.588-591
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• 2018

Baculovirus was originally isolated from the alfalfa looper and contains a 134-kbp genome with 154 open reading frames (ORF). The major capsid protein VP39 together with some minor proteins forms the nucleocapsid ($21nm{\times}260nm$) that encloses the DNA with p6.9 protein. They are double-stranded, circular, supercoiled DNA molecules in a rod-shaped capsid. Wild-type baculoviruses exhibit both lytic and occluded life cycles that develop independently throughout the three phases of virus replication. Recombinant baculoviruses can transfer their vectors and express their recombinant proteins in a wide range of mammalian cell types. Especially, inclusion of a dominant selectable marker in these baculoviral vectors can express diverse recombinant genes in many cells. Baculoviral vectors were reconstructed with cytomegalovirus (CMV) promoter,uroplakin II promoter, polyhedron promoter, vesicular stomatitis virus G (VSVG), enhanced green fluorescent protein (EGFP), protein transduction domain (PTD) gene and so on. These reconstructed vectors were infected into various cell and cell lines. We performed transfection and expression of these recombinant vectors comparison with other control vectors. From this study, we knew that transfection and expression of these recombinant vectors have higher efficacy than any control vector. This work was supported by a grant from Mid-Career Researcher Program(NRF-2016R1A2B4016552) through the National Research Foundation of Korea(NRF) funded by the Ministry of Science, ICT & Future Planning(MSIP).

• Proceedings of the Plant Resources Society of Korea Conference
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• 2018.10a
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• pp.73-73
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• 2018

Bacterial leaf blight(BLB), caused by X. oryzae pv. oryzae(Xoo), is one of the most destructive diseases of rice due to its high epidemic potential. Understanding BLB resistance at a genetic level is important to further improve the rice breeding that provides one of the best approaches to control BLB disease. In the present investigation, a collection of 192 accessions was used in the genome-wide association study (GWAS) for BLB resistance loci against four Korean races of Xoo that were represented by the prevailing BLB isolates under Xoo differential system. A total of 192 accessions of rice germplasm were selected on the basis of the bioassay using four isolated races of Xoo such as K1, K2, K3 and K3a. The selected accessions was used to prepare 384-plex genotyping by sequencing (GBS) libraries and Illumina HiSeq 2000 paired- end read was used for GBS sequencing. GWAS was conducted using T ASSEL 5.0. The T ASSEL program uses a mixed linear model (MLM). T he results of the bioassay using a selected set of 192 accessions showed that a large number of accessions (93.75%) were resistant to K1 race, while the least number of accessions (34.37%) resisted K3a race. For races K2 and K3, the resistant germplasm proportion remained between 66.67 to 70.83%. T he genotypic data produced SNP matrix for a total of 293,379 SNPs. After imputation the missing data was removed, which exhibited 34,724 SNPs for association analysis. GWAS results showed strong signals of association at a threshold of [-log10(P-value)] more than5 (K1 and K2) and more than4 (K3 and K3a) for nine of the 39 SNPs, which are plausible candidate loci of resistance genes. T hese SNP loci were positioned on rice chromosome 2, 9, and 11 for K1 and K2 races, whereas on chromosome 4, 6, 11, and 12 for K3 and K3a races. The significant loci detected have also been illustrated, NBS-LRR type disease resistance protein, SNARE domain containing protein, Histone deacetylase 19, NADP-dependent oxidoreductase, and other expressed and unknown proteins. Our results provide a better understanding of the distribution of genetic variation of BLB resistance to Korean pathogen races and breeding of resistant rice.

• Molecules and Cells
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• v.37 no.12
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• pp.873-880
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• 2014

In our previous study, miRNA-183, a miRNA in the miR-96-182-183 cluster, was significantly over-expressed in esophageal squamous cell carcinoma (ESCC). In the present study, we explored the oncogenic roles of miR-183 in ESCC by gain and loss of function analysis in an esophageal cancer cell line (EC9706). Genome-wide mRNA micro-array was applied to determine the genes that were regulated directly or indirectly by miR-183. 3'UTR luciferase reporter assay, RT-PCR, and Western blot were conducted to verify the target gene of miR-183. Cell culture results showed that miR-183 inhibited apoptosis (p < 0.05), enhanced cell proliferation (p < 0.05), and accelerated G1/S transition (p < 0.05). Moreover, the inhibitory effect of miR-183 on apoptosis was rescued when miR-183 was suppressed via miR-183 inhibitor (p < 0.05). Western blot analysis showed that the expression of programmed cell death 4 (PDCD4), which was predicted as the target gene of miR-183 by microarray profiling and bioinformatics predictions, decreased when miR-183 was over-expressed. The 3'UTR luciferase reporter assay confirmed that miR-183 directly regulated PDCD4 by binding to sequences in the 3'UTR of PDCD4. Pearson correlation analysis further confirmed the significant negative correlation between miR-183 and PDCD4 in both cell lines and in ESCC patients. Our data suggest that miR-183 might play an oncogenic role in ESCC by regulating PDCD4 expression.

• Molecules and Cells
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• v.43 no.4
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• pp.408-418
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• 2020

The sinus node (SN) is located at the apex of the cardiac conduction system, and SN dysfunction (SND)-characterized by electrical remodeling-is generally attributed to idiopathic fibrosis or ischemic injuries in the SN. SND is associated with increased risk of cardiovascular disorders, including syncope, heart failure, and atrial arrhythmias, particularly atrial fibrillation. One of the histological SND hallmarks is degenerative atrial remodeling that is associated with conduction abnormalities and increased right atrial refractoriness. Although SND is frequently accompanied by increased fibrosis in the right atrium (RA), its molecular basis still remains elusive. Therefore, we investigated whether SND can induce significant molecular changes that account for the structural remodeling of RA. Towards this, we employed a rabbit model of experimental SND, and then compared the genome-wide RNA expression profiles in RA between SND-induced rabbits and sham-operated controls to identify the differentially expressed transcripts. The accompanying gene enrichment analysis revealed extensive pro-fibrotic changes within 7 days after the SN ablation, including activation of transforming growth factor-β (TGF-β) signaling and alterations in the levels of extracellular matrix components and their regulators. Importantly, our findings suggest that periostin, a matricellular factor that regulates the development of cardiac tissue, might play a key role in mediating TGF-β-signaling-induced aberrant atrial remodeling. In conclusion, the present study provides valuable information regarding the molecular signatures underlying SND-induced atrial remodeling, and indicates that periostin can be potentially used in the diagnosis of fibroproliferative cardiac dysfunctions.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.9
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• pp.3595-3604
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• 2015

Hepatocellular carcinoma (HCC) has been one of the most fatal malignant tumors worldwide and its associated morbidity and mortality remain of significant concern. Based on in-depth reviews of serological diagnosis of HCC, in addition to AFP, there are other biomarkers: Lens culinaris agglutinin-reactive AFP (AFP-L3), descarboxyprothrombin (DCP), tyrosine kinase with Ig and eprdermal growth factor (EGF) homology domains 2 (TIE2)-espressing monocytes (TEMs), glypican-3 (GPC3), Golgi protein 73 (GP73), interleukin-6 (IL-6), and squamous cell carcinoma antigen (SCCA) have been proposed as biomarkers for the early detection of HCC. The diagnosis of HCC is primarily based on noninvasive standard imaging methods, such as ultrasound (US), dynamic multiphasic multidetector-row CT (MDCT) and magnetic resonance imaging (MRI). Some experts advocate gadolinium diethyl-enetriamine pentaacetic acid (Gd-EOB-DTPA) MRI and contrast-enhanced US as the promising imaging madalities of choice. With regard to recent advancements in tissue markers, many cuting-edge technologies using genome-wide DNA microarrays, qRT-PCR, and proteomic and inmunostaining studies have been implemented in an attempt to identify markers for early diagnosis of HCC. Only less than half of HCC patients at initial diagnosis are at an early stage treatable with curative options: local ablation, surgical resection, or liver transplant. Transarterial chemoembolization (TACE) is considered the standard of care with palliation for intermediate stage HCC. Recent innovative procedures using drug-eluting-beads and radioembolization using Yttrium-90 may exhibit beneficial effects in HCC treatment. During the past few years, several molecular targeted agents have been evaluated in clinical trials in advanced HCC. Sorafenib is currently the only approved systemic treatment for HCC. It has been approved for the therapy of asymptomatic HCC patients with well-preserved liver function who are not candidates for potentially curative treatments, such as surgical resection or liver transplantation. In the USA, Europe and particularly Japan, hepatitis C virus (HCV) related HCC accounts for most liver cancer, as compared with Asia-Pacific regions, where hepatitis B virus (HBV) may play a more important role in HCC development. HBV vaccination, while a vaccine is not yet available against HCV, has been recognized as a best primary prevention method for HBV-related HCC, although in patients already infected with HBV or HCV, secondary prevention with antiviral therapy is still a reasonable strategy. In addition to HBV and HCV, attention should be paid to other relevant HCC risk factors, including nonalcoholic fatty liver disease due to obesity and diabetes, heavy alcohol consumption, and prolonged aflatoxin exposure. Interestingly, coffee and vitamin K2 have been proven to provide protective effects against HCC. Regarding tertiary prevention of HCC recurrence after surgical resection, addition of antiviral treatment has proven to be a rational strategy.

• Proceedings of the Korean Society of Crop Science Conference
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• 2017.06a
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• pp.140-140
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• 2017

Nutritious and functional foods from crop have received great attention in recent years. Colored-grain wheat contains high phenolic compound and a large number of flavonoid. The anthocyanin and polyphenolic synthesis and accumulation is generally stimulated in response to biotic or abiotic stresses. Here, we analyzed genome wide transcripts in seedling of colored-grain wheat response to ABA and PEG treatment. About 900 and 1500 transcripts (p-value < 0.05) from ABA and PEG treatment were aligned to IWGSC1+popseq DB which is composed of over 110,000 transcripts including 100,934 coding genes. NR protein sequences of Poaceae from NCBI and protein sequence of transcription factors originated from 83 species in plant transcription factor database v3.0 were used for annotation of putative transcripts. Gene ontology analysis were conducted and KEGG mapping was performed to show expression pattern of biosynthesis genes related in flavonoid, isoflavonoid, flavons and anthocyanin biopathway. DroughtDB (http://pgsb.helmholtz-muenchen.de/droughtdb/) was used for detection of DEGs to explain that physiological and molecular drought avoidance by drought tolerance mechanisms. Drought response pathway, such as ABA signaling, water and ion channels, detoxification signaling, enzymes of osmolyte biosynthesis, phospholipid metabolism, signal transduction, and transcription factors related DEGs were selected to explain response mechanism under water deficit condition. Anthocyanin, phenol compound, and DPPH radical scavenging activity were measured and antioxidant activity enzyme assays were conducted to show biochemical adaptation under water deficit condition. Several MYB and bHLH transcription factors were up-regulated in both ABA and PEG treated condition, which means highly expressed MYB and bHLH transcription factors enhanced the expression of genes related in the biosynthesis pathways of flavonoids, such as anthocyanin and dihydroflavonols in colored wheat seedlings. Subsequently, the accumulation of total anthocyanin and phenol contents were observed in colored wheat seedlings, and antioxidant capacity was promoted by upregulation of genes involved in maintaining redox state and activation of antioxidant scavengers, such as CAT, APX, POD, and SOD in colored wheat seedlings under water deficit condition. This work may provide valuable and basic information for further investigation of the molecular responses of colored-grain wheat to water deficit stress and for further gene-based studies.

• Molecular & Cellular Toxicology
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• v.3 no.3
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• pp.190-194
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• 2007

Gastric adenocarcinoma (GA) is a major tumor type of gastric cancers and subdivides into several different tumors such as papillary, tubular mucinous, signet-ring cell and adenosquamous carcinoma according to histopatholigical determination. In other hand, GA is also subdivided into intestinal and diffuse type of adenocarcinoma by the Lauren?fs classification. In this study, we have examined differential gene expression pattern analysis of three histologically different GAs of 24 samples by using DNA microarray containing approximately 19000 genetic elements. The hierarchical clustering analysis of 24 gastric adenocarcinomas (12 of intestinal type, 7 of diffuse type and 5 of mixed type) resulted in two major subgroup on dendrogram, and two subgroups included most of intestinal and diffused type of GAs respectively. Supervised analysis of 19 intestinal and diffuse type GAs by using Wilcoxon rank T-test (P<0.01) resulted in 100 outlier genes which exactly separated intestinal and diffuse type of GA by differential gene expression. In conclusion, genome-wide analysis of gene expression of GAs suggested that GAs may subclassify as intestinal and diffused type of GA by their characteristic molecular expression. Our results also provide large-scale genetic elements which reflect molecular differences of intestinal and diffuse type of GAs, and this may facilitate to understand different molecular carcinogenesis of gastric cancer.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.8 no.2
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• pp.177-193
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• 2005

Purpose: To identify genes specifically expressed in biliary atresia, we compared the patterns of gene expression between biliary atresia and neonatal hepatitis syndrome using cDNA microarray analysis. Methods: Liver tissues were taken from livers of 11 patients (7 patients with biliary atresia and four with neonatal hepatitis) with neonatal cholestasis by needle biopsy. Normal control could be obtained from donor liver tissue during living-related liver transplantation. Total RNA was extracted from each samples and reversely transcribed to make cDNA. Then fluorescent cDNA were pooled and hybridized to the clones on the microarray. Fluorescence intensities at the immobilized targets were measured. Utilizing cDNA arrays of 4.7 K human genes, gene expression profiles were analyzed. Results: Among 4,700 microarray clones, 17 cDNA clones were significantly over-expressed in all 11 patients with neonatal cholestasis, while 20 clones were significantly decreased. Genome-wide expression analysis was carried out in livers obtained at the time of diagnosis. We could identify 49 genes, in which there showed differential expression between biliary atresia and neonatal hepatitis syndrome. Conclusion: This study shows the pattern of differentially expressed genes in biliary atresia and neonatal hepatitis syndrome. We believe that this study can contribute to the understanding of pathogenesis of neonatal cholestasis.