Minhyung Kim

Pohang University of Science and Technology, Geijitsu, Gyeongsangbuk-do, South Korea

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Publications (7)43.51 Total impact

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    ABSTRACT: Mechanisms associated with the progression of non-alcoholic fatty liver disease (NAFLD) remain unclear. We attempted to identify the pattern of altered gene expression at different time points in a high fat diet (HFD)-induced NAFLD mouse model. The early up-regulated genes are mainly involved in the innate immune responses, while the late up-regulated genes represent the inflammation processes. Although recent studies have shown that microRNAs play important roles in hepatic metabolic functions, the pivotal role of microRNAs in the progression of NAFLD is not fully understood. We investigated the functions of miR-451, which was identified as a target gene in the inflammatory process in NAFLD. miR-451 expression was significantly decreased in the palmitate (PA)-exposed HepG2 cells and in liver tissues of HFD-induced non-alcoholic steatohepatitis (NASH) mice. Its decreased expressions were also observed in liver specimens of NASH patients. In vitro analysis of the effect of miR-451 on proinflammatory cytokine provided evidence for negative regulation of PA-induced interleukin (IL)-8 and tumor necrosis factor-alpha (TNF-α) production. Furthermore, miR-451 over-expression inhibited translocation of the PA-induced NF-κB p65 subunit into the nucleus. Our result showed that Cab39 is a direct target of miRNA-451 in steatotic cells. Further study showed that AMPK activated through Cab39 inhibits NF-κB transactivation induced in steatotic HepG2 cells. miR-451 over-expression in steatotic cells significantly suppressed PA-induced inflammatory cytokine. These results provide new insights into the negative regulation of miR-451 in fatty acid-induced inflammation via the AMPK/AKT pathway and demonstrate potential therapeutic applications for miR-451 in preventing the progression from simple steatosis to severely advanced liver disease. Copyright © 2015. Published by Elsevier Ltd.
    The international journal of biochemistry & cell biology 05/2015; 91. DOI:10.1016/j.biocel.2015.04.016 · 4.24 Impact Factor
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    ABSTRACT: Recent studies reported conflicting results regarding the role of ARF6 in dendritic spine development but no clear answer for the controversy has been suggested. We found that ARF6 either positively or negatively regulates dendritic spine formation depending on neuronal maturation and activity. ARF6 activation increases the spine formation in developing neurons while it decreasing spine density in mature neurons. Genome-wide microarray analysis revealed that ARF6 activation in each stage leads to opposite expression patterns of a subset of genes that are involved in neuronal morphology. ARF6-mediated Rac1 activation via phospholipase D pathway is the coincident factor in both stages but antagonistic RhoA pathway becomes involved in the mature stage. Furthermore, blocking neuronal activity in developing neurons using TTX or enhancing the activity in mature neurons using PTX or chemical-LTP reverses the effect of ARF6 on each stage. Thus, activity-dependent dynamic changes in ARF6-mediated spine structures may play a role in structural plasticity of mature neurons. Copyright © 2015, The American Society for Biochemistry and Molecular Biology.
    Journal of Biological Chemistry 01/2015; 290(12). DOI:10.1074/jbc.M114.634527 · 4.60 Impact Factor
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    ABSTRACT: Solid-pseudopapillary neoplasm is an uncommon pancreatic tumor with distinct clinicopathologic features. Solid-pseudopapillary neoplasms are characterized by mutations in exon 3 of CTNNB1. However, little is known about the gene and microRNA expression profiles of solid-pseudopapillary neoplasms. Thus, we sought to characterize solid-pseudopapillary neoplasm-specific gene expression and identify the signaling pathways activated in these tumors. Comparisons of gene expression in solid-pseudopapillary neoplasm to pancreatic ductal carcinomas, neuroendocrine tumors, and non-neoplastic pancreatic tissues identified solid-pseudopapillary neoplasm-specific mRNA and microRNA profiles. By analyzing 1686 (1119 upregulated and 567 downregulated) genes differentially expressed in solid-pseudopapillary neoplasm, we found that the Wnt/β-catenin, Hedgehog, and androgen receptor signaling pathways, as well as genes involved in epithelial mesenchymal transition, are activated in solid-pseudopapillary neoplasms. We validated these results experimentally by assessing the expression of β-catenin, WIF-1, GLI2, androgen receptor, and epithelial-mesenchymal transition-related markers with western blotting and immunohistochemistry. Our analysis also revealed 17 microRNAs, especially the miR-200 family and miR-192/215, closely associated with the upregulated genes associated with the three pathways activated in solid-pseudopapillary neoplasm and epithelial mesenchymal transition. Our results provide insight into the molecular mechanisms underlying solid-pseudopapillary neoplasm tumorigenesis and its characteristic less epithelial cell differentiation than the other common pancreatic tumors.Modern Pathology advance online publication, 27 September 2013; doi:10.1038/modpathol.2013.154.
    Modern Pathology 09/2013; 27(4). DOI:10.1038/modpathol.2013.154 · 6.36 Impact Factor
  • Cancer Research 08/2013; 73(8 Supplement):5110-5110. DOI:10.1158/1538-7445.AM2013-5110 · 9.28 Impact Factor
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    ABSTRACT: Homeobox (HOX) family genes, major transcription factors for embryonic development, have been also implicated in vascular development and angiogenesis, particularly with regulation of genes involved in cell-cell or cell-extracellular matrix (ECM) interactions. However, the cellular and molecular functions of HOXD1 in endothelial cells (ECs) are yet to be explored. We here report that HOXD1 is prominently expressed in human ECs and regulates angiogenic activities. Knockdown of HOXD1 in ECs resulted in significant inhibition of migration and adhesion as well as tube like structure formation. These effects were correlated with the reduced expression of integrin β1 (ITGB1), an important signaling component of angiogenesis. Consistently, ITGB1 promoter activity was decreased by HOXD1 knockdown in ECs. Furthermore, we identified the putative HOXD1-binding sites in the promoter region of ITGB1. Together, these findings suggest that HOXD1 plays a significant role in EC functions by regulating the expression of ITGB1.
    Biochemical and Biophysical Research Communications 04/2011; 408(1):186-92. DOI:10.1016/j.bbrc.2011.04.017 · 2.28 Impact Factor
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    ABSTRACT: Mel-18 is a mammalian homolog of Polycomb group (PcG) genes. Microarray analysis revealed that Mel-18 expression was induced during endothelial progenitor cell (EPC) differentiation and correlates with the expression of EC-specific protein markers. Overexpression of Mel-18 promoted EPC differentiation and angiogenic activity of ECs. Accordingly, silencing Mel-18 inhibited EC migration and tube formation in vitro. Gene expression profiling showed that Mel-18 regulates angiogenic genes including kinase insert domain receptor (KDR), claudin 5, and angiopoietin-like 2. Our findings demonstrate, for the first time, that Mel-18 plays a significant role in the angiogenic function of ECs by regulating endothelial gene expression.
    Biochemical and Biophysical Research Communications 10/2010; 400(4):523-30. DOI:10.1016/j.bbrc.2010.08.086 · 2.28 Impact Factor
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    ABSTRACT: Lysine methylation within histones is crucial for transcriptional regulation and thus links chromatin states to biological outcomes. Although recent studies have extended lysine methylation to nonhistone proteins, underlying molecular mechanisms such as the upstream signaling cascade that induces lysine methylation and downstream target genes modulated by this modification have not been elucidated. Here, we show that Reptin, a chromatin-remodeling factor, is methylated at lysine 67 in hypoxic conditions by the methyltransferase G9a. Methylated Reptin binds to the promoters of a subset of hypoxia-responsive genes and negatively regulates transcription of these genes to modulate cellular responses to hypoxia.
    Molecular cell 07/2010; 39(1):71-85. DOI:10.1016/j.molcel.2010.06.008 · 14.46 Impact Factor