• 한국생물정보학회:학술대회논문집
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• 한국생물정보시스템생물학회 2006년도 Principles and Practice of Microarray for Biomedical Researchers
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• pp.83-89
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• 2006

Cellular functions are carried out by a concerted action of biochemical pathways whose components have genetic interactions. Abnormalities in the activity of the genes that constitute or modulate these pathways frequently have oncogenic implications. Therefore, identifying the upstream regulatory genes for major biochemical pathways and defining their roles in carcinogenesis can have important consequences in establishing an effective target-oriented antitumor strategy We have analyzed the gene expression profiles of human liver cancer samples using cDNA microarray chips enriched in liver and/or stomach-expressed cDNA elements, and identified groups of genes that can tell tumors from non-tumors or normal liver, or classify tumors according to clinical parameters such as tumor grade, age, and inflammation grade. We also set up a high-throughput cell-based assay system (cell chip) that can monitor the activity of major biochemical pathways through a reporter assay. Then, we applied the cell chip platform for the analysis of the HCC-associated genes discovered from transcriptome profiling, and found a number of cancer marker genes having a potential of modulating the activity of cancer-related biochemical pathways such as E2F, TCF, p53, Stat, Smad, AP-1, c-Myc, HIF and NF-kB. Some of these marker genes were previously blown to modulate these pathways, while most of the others not. Upon a fast-track phenotype analysis, a subset of the genes showed increased colony forming abilities in soft agar and altered cell morphology or adherence characteristics in the presence of purified matrix proteins. We are currently analyzing these selected marker genes in more detail for their effects on various biological Processes and for Possible clinical roles in liver cancer development.

• 약학회지
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• 제51권3호
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• pp.179-185
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• 2007

Gastric cancer is one of the most common malignancies in Korea, but the predominant molecular event underlying gastric carcinogenesis remain unknown. Recently, DNA microarray technology has enabled the comprehensive analysis of gene expression level, and as such has yielded great insight into the molecular nature of cancer, However, despite the powerful approach of this techniques, the technical artifacts and/or bias in applied array platform limited the liability of resultant tens of thousand data points from microarray experiments. Therefore, we applied two different any platforms, such as olignucleotide microarray and cDNA microarray, to identify gastric cancer related large-scale molecular signature of the same human specimens. When thirty sets of matched human gastric cancer and normal tissues subjected to oligonucleotide microarray, total 623 genes were resulted as differently expressed genes in gastric cancer compared to normal tissues, and 252 genes for cDNA microarray analysis. In addition, forty three outlier genes which reflect the characteristic expression signature of gastric cancer beyond array platform and analytical protocol was recapitulated from two different expression profile. In conclusion, we were able to identify robust large-scale molecular changes in gastric cancer by applying two different platform of DNA microarray, this may facilitate to understand molecular carcinogenesis of gastric cancer.

• Journal of Ginseng Research
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• 제41권1호
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• pp.60-68
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• 2017

Background: Various Panax ginseng cultivars exhibit a range of diversity for morphological and physiological traits. However, there are few studies on diversity of metabolic profiles and genetic background to understand the complex metabolic pathway in ginseng. Methods: To understand the complex metabolic pathway and related genes in ginseng, we tried to conduct integrated analysis of primary metabolite profiles and related gene expression using five ginseng cultivars showing different morphology. We investigated primary metabolite profiles via gas chromatography-mass spectrometry (GC-MS) and analyzed transcriptomes by Illumina sequencing using adventitious roots grown under the same conditions to elucidate the differences in metabolism underlying such genetic diversity. Results: GC-MS analysis revealed that primary metabolite profiling allowed us to classify the five cultivars into three independent groups and the grouping was also explained by eight major primary metabolites as biomarkers. We selected three cultivars (Chunpoong, Cheongsun, and Sunhyang) to represent each group and analyzed their transcriptomes. We inspected 100 unigenes involved in seven primary metabolite biosynthesis pathways and found that 21 unigenes encoding 15 enzymes were differentially expressed among the three cultivars. Integrated analysis of transcriptomes and metabolomes revealed that the ginseng cultivars differ in primary metabolites as well as in the putative genes involved in the complex process of primary metabolic pathways. Conclusion: Our data derived from this integrated analysis provide insights into the underlying complexity of genes and metabolites that co-regulate flux through these pathways in ginseng.

• 한국미생물·생명공학회지
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• 제42권1호
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• pp.18-24
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• 2014

부산 송정 연안에서 분해중인 해조류를 채집하여 cellulose 분해 미생물을 분리 동정하고 미생물의 생육조건 및 미생물이 생성한 조효소의 cellulose 분해 특성을 확인하였다. Grateloupia elliptica로부터 분리한 cellulose 분해균을 동정한 결과, Cellulophaga lytica strain로 확인되었으며, Cellulophaga lytica PKA 1005 명명하였다. C. lytica PKA 1005의 최적생육 조건을 확인한 결과, pH 7, 2% NaCl, $30^{\circ}C$ 및 배양 36시간에서 최적생육활성을 확인하였다. 또한 C. lytica PKA 1005가 생성하는 cellulose 분해 조효소는 pH 8, $35^{\circ}C$, 8% CMC 및 반응 60시간에서 최적분해활성을 보이는 것을 확인하였다.

• 미생물학회지
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• 제41권4호
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• pp.262-268
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• 2005

탄저 치사독소는 생쥐 대식세포 (RAW 264.7)의 유전자 발현에 많은 변화를 초래한다. 이들 변화를 초래하는 치사독소의 역할은 아직 확실하게 밝혀지지 ???았다. 본 연구에서는, 치사독소가 처리된 생쥐 대식세포의 단백질 프로파일을 이차원 전기영동으로 분석하였고, MALDI-TOF 질량분석기를 사용하여 해당 단백질의 질량을 측정하였다. 펩타이드 질량 분석 데이터는 ProFound 데이터베이스를 이용하여 동정하였다. 차별화되어 발현된 단백질 중에서 절단된 mitogen-activated protein kinase kinase (Mek1)와 glucose-6-phosphate dehydrogenase (G6PD)가 치사독소 처리된 대식세포에서 각각 증가하였다. 치사독소를 처리하였을 경우, Mek1의 절단은 신호전달과정을 방해하고, 증가된 G6PD는 생성된 활성산소로부터 세포를 보호하는 역할을 하는 것으로 보인다. 단백질체 분석기술은 치사독소처리에 의한 생쥐 대식세포의 세포사멸 관련 단백질을 동정하는데 도움을 주어, 치사독소의 잠정적인 기질을 찾는데 유용할 것이다.

• Journal of Cancer Prevention
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• 제22권1호
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• pp.33-39
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• 2017

Background: MicroRNAs (miRNAs) are key post-translational mechanisms which can regulate gene expression in gastric carcinogenesis. To identify miRNAs responsible for gastric carcinogenesis, we compared expression levels of miRNAs between gastric cancer tissue and non-cancerous gastric mucosa according to Helicobacter pylori status. Methods: Total RNA was extracted from the cancerous regions of formalin-fixed, paraffin-embedded tissues of H. pylori-positive (n = 8) or H. pylori-negative (n = 8) patients with an intestinal type of gastric cancer. RNA expression was analyzed using a 3,523 miRNA profiling microarray based on the Sanger miRBase. Validation analysis was performed using TaqMan miRNA assays for biopsy samples from 107 patients consisted of control and gastric cancer with or without H. pylori. And then, expression levels of miRNAs were compared according to subgroups. Results: A total of 156 miRNAs in the aberrant miRNA profiles across the miRNA microarray showed differential expression (at least a 2-fold change, P < 0.05) in cancer tissue, compared to noncancerous mucosa in both of H. pylori-negative and -positive samples. After 10 promising miRNAs were selected, validations by TaqMan miRNA assays confirmed that two miRNAs (hsa-miR-135b-5p and hsa-miR-196a-5p) were significantly increased and one miRNA (hsa-miR-145-5p) decreased in cancer tissue compared to non-cancerous gastric mucosa at H. pylori-negative group. For H. pylori-positive group, three miRNAs (hsa-miR-18a-5p, hsa-miR-135b-5p, and hsa-miR-196a-5p) were increased in cancer tissue. hsa-miR-135b-5p and hsa-miR-196a-5p were increased in gastric cancer in both of H. pylori-negative and -positive. Conclusions: miRNA expression of the gastric cancer implies that different but partially common gastric cancer carcinogenic mechanisms might exist according to H. pylori status.

• 생명과학회지
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• 제29권9호
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• pp.986-995
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• 2019

장내 미생물은 숙주의 건강을 유지하는 데 중요한 역할을 하며, 식단에 의하여직접적으로 영향을 받아 조절된다. 김치는 식이 섬유와 젖산균(LAB)이 풍부한 발효 식품이다. 발효 김치가 장내 미생물의 구성에 미치는 영향을 조사하기 위하여 6주령의 수컷 Sprague-Dawley 흰쥐 45마리를 대상으로 기본 사료(CON), 발효 김치(FK)와 키토산 첨가 발효 김치(CFK)를 각각 4주간 급여 하였다. 체중과 사료 섭취량을 매주 측정하였으며, 미생물 분석은 장내용물 수집 후 pyrosequencing을 통하여 16S rRNA 유전자 분석으로 확인 하였다. FK 및 CFK군은 대조군에 비해 체중, 사료 효율 및 혈중 triglyceride 농도가 감소한 것으로 나타났다. 장내 미생물의 다양성은 대조군에 비해 FK와 CFK군 모두에서 증가하였다. 비만과 관련된 Firmicutes 미생물이 감소한 반면, 체중 감소와 관련된 Bacteroidetes 미생물이 증가하였다. 젖산균과 체중 감소 관련 박테리아 및 butyrate 생산 박테리아는 대조군에 비해 FK 및 CFK군에서 증가하였다. 발효 김치는 비만을 억제하고 장내 유익한 미생물의 성장을 촉진하였다.

• Journal of Ginseng Research
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• 제47권1호
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• pp.44-53
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• 2023

Background: The genus Panax in the Araliaceae family has been used as traditional medicinal plants worldwide and is known to biosynthesize ginsenosides and phytosterols. However, genetic variation between Panax species has influenced their biosynthetic pathways is not fully understood. Methods: Simultaneous analysis of transcriptomes and metabolomes obtained from adventitious roots of two tetraploid species (Panax ginseng and P. quinquefolius) and two diploid species (P. notoginseng and P. vietnamensis) revealed the diversity of their metabolites and related gene expression profiles. Results: The transcriptome analysis showed that 2,3-OXIDOSQUALENE CYCLASEs (OSCs) involved in phytosterol biosynthesis are upregulated in the diploid species, while the expression of OSCs contributing to ginsenoside biosynthesis is higher in the tetraploid species. In agreement with these results, the contents of dammarenediol-type ginsenosides were higher in the tetraploid species relative to the diploid species. Conclusion: These results suggest that a whole-genome duplication event has influenced the triterpene biosynthesis pathway in tetraploid Panax species during their evolution or ecological adaptation. This study provides a basis for further efforts to explore the genetic variation of the Panax genus.

• 생명과학회지
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• 제33권6호
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• pp.481-489
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• 2023

콩을 주원료로 발효하여 제조되는 조미료인 간장의 맛과 품질은 발효 중 미생물의 대사에 큰 영향을 받는 것으로 알려져 있다. 본 연구에서는 개량식 간장의 초기 발효과정에서 미생물학적 특성을 분석하기 위해 본 연구원 보유 미생물을 스타터로 활용한 메주와 염수를 이용하여 간장을 제조하였으며, 5주간의 발효과정에서 발효 1주차, 3주차, 5주차 간장 시료의 16S rRNA 유전자를 정량적으로 분석하였다. 발효기간에 따른 미생물의 분포를 분석한 결과 발효 1주차 간장에서는 Halomonadaceae과 미생물이 89.83%를 차지하였으며, 3주차 간장과 5주차 간장에서는 각각 14.46%, 13.78%로 나타나 매우 유의한 수준으로 높은 것으로 나타났다. 종 수준에서 미생물 분포를 분석한 결과 발효 1주차 간장에서는 Chromohalobacter beijerinckii와 Chromohalobacter canadensis가 가장 우점하는 미생물로 나타났으나, 발효 3주차와 5주차 간장에서는 Bacillus subtilis, Pediococcus acidilactici, Enterococcus faecalis가 상대적으로 높은 비율로 우점하는 것으로 나타났다. 또한, 발효과정 중 우점 미생물의 분포 상관관계를 분석한 결과 Chromohalobacter는 Bacillus, Enterococcus와 음의 상관관계를 나타냈다. Beta-diversity 분석 결과 발효 1주차 간장의 미생물 군집은 발효 3주차, 5주차 간장의 미생물 군집과 통계적으로 유의한 수준의 차이가 있는 것으로 나타났으나, 발효 3주차 간장과 5주차 간장의 미생물 군집 사이에는 유의한 차이가 없는 것으로 나타났다. 간장 발효기간별 바이오 마커를 분석하기 위해 선형 판별 효과 크기 분석을 수행한 결과 호염성 미생물, Bacillus 속 미생물, 유산균의 상대적인 풍부도가 발효기간에 따른 미생물 군집 구조 차이에 큰 영향을 미치는 것으로 나타났다.

• BMB Reports
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• 제56권10호
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• pp.563-568
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• 2023

DNA methylation regulates gene expression and contributes to tumorigenesis in the early stages of cancer. In colorectal cancer (CRC), CpG island methylator phenotype (CIMP) is recognized as a distinct subset that is associated with specific molecular and clinical features. In this study, we investigated the genome-wide DNA methylation patterns among patients with CRC. The methylation data of 1 unmatched normal, 142 adjacent normal, and 294 tumor samples were analyzed. We identified 40,003 differentially methylated positions with 6,933 (79.8%) hypermethylated and 16,145 (51.6%) hypomethylated probes in the genic region. Hypermethylated probes were predominantly found in promoter-like regions, CpG islands, and N shore sites; hypomethylated probes were enriched in open-sea regions. CRC tumors were categorized into three CIMP subgroups, with 90 (30.6%) in the CIMP-high (CIMP-H), 115 (39.1%) in the CIMP-low (CIMP-L), and 89 (30.3%) in the non-CIMP group. The CIMP-H group was associated with microsatellite instability-high tumors, hypermethylation of MLH1, older age, and right-sided tumors. Our results showed that genome-wide methylation analyses classified patients with CRC into three subgroups according to CIMP levels, with clinical and molecular features consistent with previous data.