• IMMUNE NETWORK
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• v.11 no.1
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• pp.11-41
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• 2011

The discovery of microRNA (miRNA) is one of the major scientific breakthroughs in recent years and has revolutionized current cell biology and medical science. miRNAs are small (19~25nt) noncoding RNA molecules that post-transcriptionally regulate gene expression by targeting the 3' untranslated region (3'UTR) of specific messenger RNAs (mRNAs) for degradation of translation repression. Genetic ablation of the miRNA machinery, as well as loss or degradation of certain individual miRNAs, severely compromises immune development and response, and can lead to immune disorders. Several sophisticated regulatory mechanisms are used to maintain immune homeostasis. Regulatory T (Treg) cells are essential for maintaining peripheral tolerance, preventing autoimmune diseases and limiting chronic inflammatory diseases. Recent publications have provided compelling evidence that miRNAs are highly expressed in Treg cells, that the expression of Foxp3 is controlled by miRNAs and that a range of miRNAs are involved in the regulation of immunity. A large number of studies have reported links between alterations of miRNA homeostasis and pathological conditions such as cancer, cardiovascular disease and diabetes, as well as psychiatric and neurological diseases. Although it is still unclear how miRNA controls Treg cell development and function, recent studies certainly indicate that this topic will be the subject of further research. The specific circulating miRNA species may also be useful for the diagnosis, classification, prognosis of diseases and prediction of the therapeutic response. An explosive literature has focussed on the role of miRNA. In this review, I briefly summarize the current studies about the role of miRNAs in Treg cells and in the regulation of the innate and adaptive immune response. I also review the explosive current studies about clinical application of miRNA.

• Journal of Microbiology
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• v.41 no.3
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• pp.259-261
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• 2003

The nsdD gene has been predicted to encode a GATA type transcription factor with the type IVb zinc finger DNA binding domain functions in activating sexual development of A. nidulans. In several allelic mutants of nsdD producing truncated NsdD polypeptides lacking the C-terminal zinc finger, the transcription level of nsdD gene was greatly increased. Also in an over-expressed mutant, the transcription under its own promoter was reduced. These results suggest that the expression of nsdD is negatively autoregulated. When the nsdD gene was over-expressed, cleistothecia were formed in excess amounts even in the presence of 0.6 M KC1 that inhibited sexual development of the wild type. Northern blot analysis revealed that the expression of nsdD was repressed by 0.6 M KC1. These results strongly suggest that the inhibition of sexual development by salts was carried out via the nsdD involved regulatory network.

• Molecules and Cells
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• v.39 no.5
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• pp.367-374
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• 2016

Since the RNA world hypothesis was proposed, a large number of regulatory noncoding RNAs (ncRNAs) have been identified in many species, ranging from microorganisms to mammals. During the characterization of these newly discovered RNAs, RNAs having both coding and noncoding functions were discovered, and these were considered bifunctional RNAs. The recent use of computational and high-throughput experimental approaches has revealed increasing evidence of various sources of bifunctional RNAs, such as protein-coding mRNAs with a noncoding isoform and long ncRNAs bearing a small open reading frame. Therefore, the genomic diversity of Janusfaced RNA molecules that have dual characteristics of coding and noncoding indicates that the functional roles of RNAs have to be revisited in cells on a genome-wide scale. Such studies would allow us to further understand the complex gene-regulatory network in cells. In this review, we discuss three major genomic sources of bifunctional RNAs and present a handful of examples of bifunctional RNA along with their functional roles.

• Journal of Internet Computing and Services
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• v.18 no.5
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• pp.47-53
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• 2017

In past few years, high-throughput sequencing, big-data generation, cloud computing, and computational biology are revolutionary. RNA sequencing is emerging as an attractive alternative to DNA microarrays. And the methods for constructing Gene Regulatory Network (GRN) from RNA-Seq are extremely lacking and urgently required. Because GRN has obtained substantial observation from genomics and bioinformatics, an elementary requirement of the GRN has been to maximize distinguishable genes. Despite of RNA sequencing techniques to generate a big amount of data, there are few computational methods to exploit the huge amount of the big data. Therefore, we have suggested a novel gene selection algorithm combining Support Vector Machines and Intensity-dependent normalization, which uses log differential expression ratio in RNAseq. It is an extended variation of support vector machine recursive feature elimination (SVM-RFE) algorithm. This algorithm accomplishes minimum relevancy with subsets of Big-Data, such as NCBI-GEO. The proposed algorithm was compared to the existing one which uses gene expression profiling DNA microarrays. It finds that the proposed algorithm have provided as convenient and quick method than previous because it uses all functions in R package and have more improvement with regard to the classification accuracy based on gene ontology and time consuming in terms of Big-Data. The comparison was performed based on the number of genes selected in RNAseq Big-Data.

• Molecules and Cells
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• v.41 no.5
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• pp.381-389
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• 2018

ARF is a tumor suppressor protein that has a pivotal role in the prevention of cancer development through regulating cell proliferation, senescence, and apoptosis. As a factor that induces senescence, the role of ARF as a tumor suppressor is closely linked to the p53-MDM2 axis, which is a key process that restrains tumor formation. Thus, many cancer cells either lack a functional ARF or p53, which enables them to evade cell oncogenic stress-mediated cycle arrest, senescence, or apoptosis. In particular, the ARF gene is a frequent target of genetic and epigenetic alterations including promoter hyper-methylation or gene deletion. However, as many cancer cells still express ARF, pathways that negatively modulate transcriptional or post-translational regulation of ARF could be potentially important means for cancer cells to induce cellular proliferation. These recent findings of regulators affecting ARF protein stability along with its low levels in numerous human cancers indicate the significance of an ARF post-translational mechanism in cancers. Novel findings of regulators stimulating or suppressing ARF function would provide new therapeutic targets to manage cancer- and senescence-related diseases. In this review, we present the current knowledge on the regulation and alterations of ARF expression in human cancers, and indicate the importance of regulators of ARF as a prognostic marker and in potential therapeutic strategies.

• Proceedings of the Korea Information Processing Society Conference
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• 2005.11a
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• pp.603-606
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• 2005

하나의 유전자는 또 다른 유전자의 단백질과 프로모터 영역에서 Binding 함으로써 그 유전자의 발현에 영향을 미칠 수 있다. 이러한 두 유전자간의 조절 상호 작용을 유전자 조절망이라 하며 유전체의 핵심적인 기능을 보다 간결하게 표현하는 조절망을 설계할 수 있다. 대표적인 설계 방법으로는 Time-Series Data 를 이용한 방법과 Steady-State Data 를 이용하는 방법이 있으며 이 논문에서는 Steady-State Data 즉, Knock-out Data 를 이용하여 유전자 조절망을 재구성함으로써 기존의 방법을 개선하여 보다 정확한 결과 예측을 목표로 한다.

• Molecules and Cells
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• v.28 no.2
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• pp.75-80
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• 2009

The cyclic environmental conditions brought about by the 24 h rotation of the earth have allowed the evolution of endogenous circadian clocks that control the temporal alignment of behaviour and physiology, including the uptake and processing of nutrients. Both metabolic and circadian regulatory systems are built upon a complex feedback network connecting centres of the central nervous system and different peripheral tissues. Emerging evidence suggests that circadian clock function is closely linked to metabolic homeostasis and that rhythm disruption can contribute to the development of metabolic disease. At the same time, metabolic processes feed back into the circadian clock, affecting clock gene expression and timing of behaviour. In this review, we summarize the experimental evidence for this bimodal interaction, with a focus on the molecular mechanisms mediating this exchange, and outline the implications for clock-based and metabolic diseases.

• IMMUNE NETWORK
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• v.2 no.1
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• pp.1-5
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• 2002

Estimated number of adults and children newly infected with HIV-1 during 2001 alone is 5 million in total. An effective vaccine, in addition to education & public health approaches, has been believed to be the best option to stop the HIV-1 transmission, especially for developing countries. Among AIDS vaccine candidates, DNA vaccine is relatively safe and, in a certain extent, mimics some attributes of live attenuated vaccine, with regard to in vivo gene expression & the type of immunity induced. We recently demonstrated that DNA vaccines expressing SIVmac239 structural and regulatory genes, augmented with coadministration of IL-12 mutant induced the strongest T cell responses, resulting in low to undetectable setpoint viral loads, stable $CD4^+$ T cell counts, and no evidence of clinical diseases or mortality by day 420 after challenge. This finding is the second demonstration, following the protective result of live attenuated SIV vaccine in SIVmac-rhesus monkey model, which was known to have safety problem. So, our DNA vaccines could give a significant impact on HIV-1 epidemic by slowing or stopping the spread of HIV-1, leading to eventual eradication of HIV-1 and AIDS in the population.

• Journal of Animal Science and Technology
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• v.54 no.6
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• pp.383-394
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• 2012

Microarray analyses provide information that can be used to enhance the efficiency of livestock production. For example, microarray profiling can potentially identify the biological processes responsible for the phenotypic characteristics of porcine liver. We performed transcriptome profiling to identify differentially expressed genes (DEGs) in liver of pigs from two breeds, the Korean native pigs (KNP) and Yorkshire pigs. We correctly identified expected DEGs using factor analysis for robust microarray summarization (FARMS) and robust multi-array average (RMA) strategies. We identified 366 DEGs in liver (p<0.05, fold-change>2). We also performed functional analyses, including gene ontology and molecular network analyses. In addition, we identified the regulatory relationship between DEGs and their transcription factors using in silico and qRT-PCR analysis. Our findings suggest that DEGs and their transcription factors may have a potential role in adipogenesis and/or lipid deposition in liver tissues of two pig breeds.

• Journal of Life Science
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• v.19 no.8
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• pp.1159-1163
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• 2009

It has been postulated that endoplasmic (ER) stress is involved in the development of several diseases. However, the detailed molecular mechanisms have not been fully understood. Therefore, we characterized a genetic network of genes induced by ER stress using cDNA microarray and gene set expression coherence analysis (GSECA), and identified gene function as well as several transcription regulators associated with ER stress. We analyzed time-dependent gene expression profiles in thapsigargin-treated Sk-Hep1 using an oligonucleotide expression chip, and then selected functional gene sets with significantly high expression coherence which was processed into functional clusters according to the expression similarities. The functions related to sugar binding, lysosome, ribosomal protein, ER lumen, and ER to golgi transport increased, whereas the functions with mRNA processing, DNA replication, DNA repair, cell cycle, electron transport chain and helicase activity decreased. Furthermore, functional clusters were investigated for the enrichment of regulatory motifs using GSECA, and several transcriptional regulators associated with regulation of ER-induced gene expression were found.