• BMB Reports
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• v.50 no.8
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• pp.411-416
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• 2017

The endoplasmic reticulum (ER) membrane protein complex subunit 6 (EMC6) is a novel human autophagy-related molecule. Here, using tissue microarray and immunohistochemistry, we report that EMC6 protein is lost or reduced in glandular cells of patients with gastric adenocarcinoma, compared to normal stomach mucosa. Overexpression of EMC6 in gastric cancer cells inhibited cell growth, migration, invasion, and induced apoptosis and cell cycle arrest at S-phase. Further investigation suggested that EMC6 overexpression in BGC823 human adenocarcinoma gastric cancer cells reduced tumorigenicity in a xenograft model, demonstrating that EMC6 has the characteristics of a tumor suppressor. This is the first study to show that EMC6 induces cell death in gastric cancer cells. The molecular mechanism of how EMC6 functions as a tumor suppressor needs to be further explored.

• Journal of Plant Biotechnology
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• v.34 no.3
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• pp.167-172
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• 2007

A tomato zinc-finger protein gene, LeZFP1, encoding the Cys2/His2-type zinc-finger transcription factor was searched from cDNA microarray analysis of gene expression following induction of the overexpressed tomato transgenic plants showing resistance for pathogen and abiotic stresses. The full-length cDNA of LeZFP1 encoded a protein of 261 amino acid residues. Analysis of the deduced amino acid sequence of LeZFP1 revealed that it shares high sequence identity with pepper CAZFP1 (81% identity). We found that single copy of LeZFP1 gene is present in the tomato genome through southern blot analysis. The LeZFP1 transcripts were constitutively expressed in the tomato mature and young leaves, but were detectable weakly in the flower, stem and root. The LeZFP1 transcripts were significantly reduced in treated leaf tissues with NaCl and mannitol. The LeZFP1 gene was induced by oxidative stress especially. Our results indicated that LeZFP1 may play a role function involved in oxidative stress signaling pathways.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.3
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• pp.1003-1008
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• 2016

Breast cancer is now the leading cause of cancer death in women worldwide. Cancer progression is driven not only by cancer cell intrinsic alterations and interactions with tumor microenvironment, but also by systemic effects. Integration of multiple profiling data may provide insights into the underlying molecular mechanisms of complex systemic processes. We performed a bioinformatic analysis of two public available microarray datasets for breast tumor stroma and peripheral blood mononuclear cells, featuring integrated transcriptomics data, protein-protein interactions (PPIs) and protein subcellular localization, to identify genes and biological pathways that contribute to dialogue between tumor stroma and the peripheral circulation. Genes of the integrin family as well as CXCR4 proved to be hub nodes of the crosstalk network and may play an important role in response to stroma-derived chemoattractants. This study pointed to potential for development of therapeutic strategies that target systemic signals travelling through the circulation and interdict tumor cell recruitment.

• Proceedings of the Korean Society of Toxicology Conference
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• 2006.11a
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• pp.19-24
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• 2006

Mothers against decapentaplegic homolog 4 (SMAD4) is a tumor suppressor gene associated with gastrointestinal carcinogenesis. The aim of the present study was to characterize more precisely its role in the development and progression of human gastric carcinoma. In this study, using tissue microarray analysis of 283 gastric cancers and related lesions, we found loss of SMAD4 protein expression in the cytoplasm (36/114, 32%) and in the nucleus (46/114, 40%) of gastric cancer cells. The loss of nuclear SMAD4 expression in primary tumors correlated significantly with poor survival, and was an independent prognostic marker in multivariate analysis. We also found a substantial decrease in SMAD4 expression at both the RNA and protein level in several human gastric carcinoma cell lines. To identify the genetic and/or epigenetic mechanisms of altered SMAD4 expression in gastric carcinoma, loss of heterozygosity (LOH), promoter hypermethylation, and exon mutations were examined. We found that LOH (20/70, 29%) and promoter hypermethylation (4/73, 5%) were associated with the loss of SMAD4 expression. SMAD4 protein levels wore also affected in certain gastric carcinoma cell lines following incubation with Mc132, a proteasome inhibitor. Taken together, our results indicate that the loss of SMAD4, especially loss of nuclear SMAD4 expression, is involved in gastric cancer progression. The loss of SMAD4 in gastric carcinomas is due to several mechanisms, including LOH, hypermethylation, and proteasome degradation.

• Journal of Physiology & Pathology in Korean Medicine
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• v.16 no.5
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• pp.1025-1034
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• 2002

The herbal extract (YMT_02) is a modified herbal extracts from Yukmijihwang-tang (YMJ) to promote memory-enhancing. The YMJ extracts has been widely used as an anti-aging herbal medicine for hundred years in Asian countries. The purpose of this study is to; 1) quantitatively evaluate the memory-enhancing effect of YMT_02 by behavior task, 2) identify candidate genes responsible for enhancing memory by cDNA microarray and 3) assess the anti-oxidant effect of YMT_02 on PC12 cell. Memory retention abilities are addressed by passive avoidance task with Sprague-Dawley (SD) male rat. Before the training session, the rats are subdivided into four groups and administrated with YMT_02, Ginkgo biloba, Soya lecithin and normal saline for 10 days. The retention test was performed. 24 hours after the training session. The retention time of the YMT_02 group was significantly (p<0.05) delayed (～100%), whereas Ginkgo biloba and Soya lecithin treatment delayed 20% and 10% respectively. The hippocampi of YMT_02 and control group were dissected and mANA was further purified. After synthesizing cDNA using oligo-dT primer, the cDNA were applied to Incyte rat GEMTM 2 cDNA microarray. The microarray results show that prealbumin(transthyretin), phosphotidylethanolamine N-methyltransferase, and PEP-19 are expressed abundantly in the YMT_02 treated group. Especially, PEP-19 is a neuron-specific protein, which inhibits apoptotic processes in neuronal cell. On the other hand, transcripts of RAB15, glutamate receptor subunit 2 and CDK108 are abundant in control group. Besides, neuronal genes involved in neuronal death or neurodegeneration such as neuronal-pentraxin and spectrin are abundantly expressed in control group. Additionally, the YMT_02 shows an anti oxidative effect in the PC12 cell. The list of differentially expressed genes may implicate further insight on the action and mechanism behind the memory-enhancing effect of herbal extracts YMT_02, for example, anti-apoptotic, anti-oxidative, and neuroprotective effects.

• Journal of Embryo Transfer
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• v.23 no.3
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• pp.211-216
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• 2008

This study was carried out to investigate inflammation-related gene expression altered in ovary and endometrium of Korean cattle with reproductive disorders using microarray. In the present study, nine inflammation-related differential1y expressed genes (DEGs) were identified in the cystic ovary and endometrium with endometritis. In the follicular cyst, eotaxin and alpha-2-HS-glycoprotein (AHSG) were up-regulated, whereas complement component 3 (C3) and oxidised low density lipoprotein (lectin-like) receptor 1 (OLR1) were down-regulated. Complement component 4A (C4A) was up-regulated in luteal cyst. In the endometritis, chemokine 1igand l and 2 (CXCL1 and CXCL2), protein C (inactivator of coagulation factors Va and VIIIa), and complement component C5 were up-regulated, whereas kininogen was down-regulated. Of these genes, we focused on eotaxin and kininogen, which were highly regulated in the follicular cyst and endometritis, respectively and on C3 commonly regulated in both reproductive disorders. The microarray data of eotaxin, kininogen, and C3 were validated by semi-quantitative PCR. Consistent with microarray data, eotaxin was up-regulated by 4-fold in the follicular cyst, while kininogen was down-regulated by 5-fold in the endometritis. C3 was down-regulated in the both follicular cyst and endometritis. Our results suggest that these inflammation-related genes could be useful markers for diagnosis of cystic ovary and endometritis of Korean cattle.

• Journal of Life Science
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• v.30 no.9
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• pp.772-782
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• 2020

Skeletal muscle differentiation or myogenesis is important to maintain muscle mass and metabolic homeostasis. Muscle-specific microRNAs (miRNAs) are known to play a critical role in skeletal myogenic differentiation. In this study, we examined the expression profiling of miRNAs during myogenic differentiation in rat L6 myoblasts using rat miRNA microarrays. We identified the upregulated expression of miR-128 as well as several well-known myogenic miRNAs, including miR-1, miR-133b, and miR-206. We additionally confirmed the increased expression of miR-128 observed on microarray through quantitative real-time PCR (qRT-PCR), which showed similarly upregulated expression of both primary miR-128 and mature miR-128, consistent with the microarray findings. Furthermore, transfection of miR-128 into rat L6 myoblasts induced gene expression of myogenic markers such as muscle creatine kinase (MCK), myogenin, and myosin heavy chain (MHC). Protein expression of MHC was increased as well. Inhibition of miR-128 by inhibitory peptide nucleic acids (PNAs) blocked the expression of those myogenic markers. In addition, the transfection of miR-128 into rat L6 myoblasts enhanced the phosphorylation of Erk and Akt proteins stimulated by insulin, while simultaneously reversing the inhibited phosphorylation of Erk and Akt due to insulin resistance. These findings suggest that miR-128 may play important roles in myogenic differentiation and insulin signaling.

• Horticultural Science & Technology
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• v.31 no.6
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• pp.748-755
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• 2013

This study was conducted to find a salt tolerance gene in Brassica rapa. In order to meet this objective, we analyzed data from a KBGP-24K oligo chip [BrEMD (Brassica rapa EST and microarray database)] of the B. rapa ssp. pekinensis 'Chiifu' under salt stress (250 mM NaCl). From the B. rapa KBGP-24K microarray chip analysis, 202 salt-responsive unigenes were primarily selected under salt stress. Of these, a gene with unknown function but known full-length sequence was chosen to closely investigate the gene function. The selected gene was named BrSSR (B. rapa salt stress resistance). BrSSR contains a 285 bp open reading frame encoding a putative 94-amino acid protein, and a DUF581 domain. The pSL94 vector was designed to over-express BrSSR, and was used to transform tobacco plants for salt tolerance analysis. T1 transgenic tobacco plants that over-expressed BrSSR were selected by PCR and DNA blot analyses. Quantitative real-time RT PCR revealed that the expression of BrSSR in transgenic tobacco plants increased by approximately 3.8-fold. Similar results were obtained by RNA blot analysis. Phenotypic characteristics analysis showed that transgenic tobacco plants with over-expressed BrSSR were more salt-tolerant than the wild type control under 250 mM NaCl for 5 days. Based on these results, we hypothesized that the over-expression of BrSSR may be closely related to the enhancement of salt tolerance.

• Journal of Life Science
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• v.19 no.12
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• pp.1787-1793
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• 2009

To investigate whether caffeic acid phenethyl ester (CAPE) could affect cancer cell viabilities and gene expression, human colorectal HCT116 cells were incubated with CAPE. CAPE decreased cancer cell viabilities and induced apoptosis in a dose-dependent manner. To analyse differently expressed genes by CAPE, we performed oligo DNA microarray analysis. We found that 266 genes were up-regulated more than twofold, whereas 143 genes were down-regulated more than twofold by 24 hr of treatment with $20{\mu}M$ CAPE. Among the up-regulated genes, we selected 3 genes (NSAID activated gene-1 [NAG-1], cyclin-dependent kinase inhibitor 1A [CDKN1A, p21] and growth arrest and DNA-damage-inducible alpha [GADD45A]) and performed reverse-transcription PCR to confirm microarray data. In addition, we found that CAPE increased NAG-1 gene and NAG-1 protein expression in a dose-dependent manner. And, several other phytochemicals (resveratrol, genistein, daidzein and capsaicin) also could induce NAG-1 expression in human colorectal HCT116 cells. However, CAPE was the highest inducer of NAG-1, even in low concentrations. Overall, these results imply that cancer cell death by CAPE is closely related with over-expression of NAG-1.

• Microbiology and Biotechnology Letters
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• v.38 no.4
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• pp.442-447
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• 2010

We investigated anti-cancer and anti-proliferative activity of allicin and analyzed global gene expression changes by allicin treatment in human colorectal HCT116 cells. As a result, allicin decreased cell viabilities in a dose and time-dependent manner and induced apoptosis. Oligo DNA microarray analysis, we found that 7,840 genes were up-regulated more than 2-folds, whereas 10,010 genes were down-regulated more than 2-folds by $50\;{\mu}M$ allicin treatment. To confirm specific gene expressions, we performed RT-PCR. Consistent with the results of DNA microarray analysis, allicin dramatically induced ATF3 and NAG1 gene expression. Interestingly, NAG-1 protein expression was dependent on p53 presence. Taken together, our present results increase the knowledge of the molecular mechanism of anti-cancer and anti-proliferative activity mediated by allciin in human colorectal cancer cell.