• Asian Pacific Journal of Cancer Prevention
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• v.13 no.7
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• pp.3173-3178
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• 2012

The enhancer of zeste homolog 2 (EZH2) methyl transferase and histone 3 lysine 27 (H3K27me3) protein can repress gene transcription, and their aberrant expression has been observed in various human cancers. This study determined their expression levels in gastric cancer tissues with reference to clinicopathological features and patient survival. We collected 117 gastric cancer and corresponding normal tissues for immunohistochemistry analysis. In gastric cancers, 82/117 (70.1%) were positive for EZH2 and 66/117 (56.4%) for H3K27me3 proteins in contrast to only 5.41% and 7.25% of normal gastric mucosa specimens, respectively. Kaplan-Meier survival data showed the average overall and disease-free survival of EZH2 high expression patients was 25.2 and 20.2 months, respectively, shorter than that with EZH2 low expression (40.5 and 35.9 months). The average overall survival and disease-free survival of high H3K27me3 expression patients was 23.4 and 17.4 months, shorter than without H3K27me3 expression (37.6 and 34.5 months). The average overall survival and disease-free survival of patients with both EZH2 and H3K27me3 expression was 18.8 and 12.9 months, respectively, shorter than that with either alone (34.7 and 31.2 months) or with low levels of both (43.9 and 39.9 months). Multivariate Cox regression analysis showed that H3K27me3 and EZH2 expression, tumor size differentiation and clinical stage were all independent prognostic factors for predicting patient survival. This study demonstrated that detection of both EZH2 and H3K27me3 proteins can predict poor survival of gastric cancer patients, superior to single protein detection. In addition, H3K27me3 and EZH2 protein expression could predict lymph node metastasis.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.2
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• pp.999-1003
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• 2014

Objective: To validate the relationship between MACC1 and 6-phosphofructo-2-kinase/fructose 2, 6 bisphosphatase (PFKFB2) expression as well as its clinicopathological features and prognostic significance in hepatocellular carcinoma. Methods: By using immunohistochemistry, we investigated the MACC1 and PFKFB2 protein expression in 60 pairs of hepatocellular carcinoma and corresponding non-tumor tissues. Using the Mann-Whitney U test, the Chi-square test, Kaplan-Meier survival analysis, Cox proportional hazard regression analysis and Spearman analysis, we studied the relationship between MACC1 and PFKFB2 protein expression and postoperative overall survival (OS) of the HCC patients. Results: MACC1 and PFKFB2 positive staining rates were significantly higher in hepatocellular carcinoma than in the corresponding nontumor tissues (P=0.012 and 0.04, respectively). The clinicopathological features evaluation revealed that positive expression of MACC1 was associated with a high Edmondson classification (P=0.007) and advanced TNM stage (P=0.027). Similar findings were evident for PFKFB2 expression (P=0.002 and P=0.027). MACC1 and PFKFB2 positive expression was associated with a lower OS rate (P=0.004 and 0.03, respectively). Kaplan-Meier survival and Cox proportional hazard regression analyses revealed MACC1 positive expression to be a prognostic factor for postoperative OS, but PFKFB was not. Conclusion: Highly expressed MACC1 and PFKFB2 protein were associated with TNM stage, Edmondson-Steier classification and overall survival. MACC1 may affect tumor metabolism partly through expression and phophorylation of PFKFB2.

• Asian-Australasian Journal of Animal Sciences
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• v.28 no.6
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• pp.870-875
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• 2015

The purpose of this study was to investigate the alternative splicing in equine cordon-bleu WH2 repeat protein-like 1 (COBLL1) gene that was identified in horse muscle and blood leukocytes, and to predict functional consequences of alternative splicing by bioinformatics analysis. In a previous study, RNA-seq analysis predicted the presence of alternative spliced isoforms of equine COBLL1, namely COBLL1a as a long form and COBLL1b as a short form. In this study, we validated two isoforms of COBLL1 transcripts in horse tissues by the real-time polymerase chain reaction, and cloned them for Sanger sequencing. The sequencing results showed that the alternative splicing occurs at exon 9. Prediction of protein structure of these isoforms revealed three putative phosphorylation sites at the amino acid sequences encoded in exon 9, which is deleted in COBLL1b. In expression analysis, it was found that COBLL1b was expressed ubiquitously and equivalently in all the analyzed tissues, whereas COBLL1a showed strong expression in kidney, spinal cord and lung, moderate expression in heart and skeletal muscle, and low expression in thyroid and colon. In muscle, both COBLL1a and COBLL1b expression decreased after exercise. It is assumed that the regulation of COBLL1 expression may be important for regulating glucose level or switching of energy source, possibly through an insulin signaling pathway, in muscle after exercise. Further study is warranted to reveal the functional importance of COBLL1 on athletic performance in race horses.

• Journal of Animal Science and Technology
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• v.44 no.6
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• pp.677-684
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• 2002

We have investigated the expression patterns of candidates for growth stage specifically expressed genes. The expression patterns of the EPV20, aldolase A, Translationally Controlled Tumor Protein (TCTP) and Adipocyte Differentiation Related Protein (ADRP) were examined by semiquantitative RT-PCR and northern blot analysis in skeletal muscle tissues of Hanwoo, especially in the longissimus dorsi at various growth stages. The EPV20 mRNA was expressed in longissimus dorsi tissue of Hanwoo, but there was no difference of expression levels during growth stages. Though the aldolase A gene was reported to be muscle-specific and regulated at developmental stages, the expression levels of aldolase A mRNA in the longissimus dorsi tissues showed little differences at various growth stages. The expression levels of TCTP which was reported as growth-related protein regulated at translation step were gradually increased during growth of Hanwoo. The expression levels of ADRP mRNA were rapidly increased at 24-month-old longissimus dorsi tissue of Hanwoo, and decreased at 30-month-old. Our data suggest that the ADRP gene show as growth-stage dependent expression and is related to fat deposition within muscular tissue.

• Journal of Gastric Cancer
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• v.5 no.1
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• pp.34-39
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• 2005

Purpose: KLF6, a member of the KLF family, is a ubiquitous zinc finger tumor suppressor protein that is mutated in several human cancers. Our aim was to determine whether the expression pattern of KLF6 might be associated with gastric cancer development and, if so, to determine to which pathologic parameter it is linked. Materials and Methods: For the construction of the gastric cancer tissue microarray, 85 paraffin-embedded tissues containing gastric cancer areas were cored 3 times and transferred to the recipient master block. The expression pattern of KLF6 was examined on tissue microarray slides by using immunohistochemistry and was compared with pathologic parameters, including histologic type, depth of invasion, lymph node metastasis, and peritoneal dissemination. Results: The KLF6 protein was expressed on superficial and foveolar epithelial cells in the gastric mucosa. We found loss of KLF6 expression in 28 ($32.9\%$) of the 85 gastric cancer tissues. There was a significant correlation between loss of KLF6 expression and lymph-node metastasis. However, other pathologic parameters, such as histologic type, depth of invasion, and peritoneal dissemination, were not statistically associated with loss of KLF6 expression. Conclusion: Our findings suggest that loss of KLF6 expression may contribute to abnormal regulation of gastrointestinal epithelial cell growth and differentiation and to the development and/or progression of Korean gastric cancer.

• Journal of Life Science
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• v.29 no.6
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• pp.631-636
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• 2019

A new nitric oxide-induced (NOI) gene was isolated by screening ESTs from a cDNA library of dehydration-treated fibrous roots of sweetpotato (Ipomoea batatas). The 720 bp cDNA fragment, IbNOI, was sequenced, from which a 77 amino acid residue protein was deduced. A search of the protein BLAST database identified significant similarity to other plant NOI protein sequences. Quantitative RT-PCR analysis revealed diverse expression patterns of IbNOI in various tissues of the intact sweetpotato plant, and in leaves exposed to different stresses. The IbNOI gene was highly expressed in storage roots and suspension-cultured cells. In leaf tissues, IbNOI showed strong expression during sodium nitroprusside (SNP)-induced NO accumulation and chemical stress treatments. Expression of IbNOI was also induced under various abiotic stress conditions, such as dehydration, salt, and bacterial pathogen infection. These results suggest that IbNOI is involved in plant responses to diverse abiotic stresses and pathogen infection through a NO-related pathway.

• Annals of Hepato-Biliary-Pancreatic Surgery
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• v.26 no.1
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• pp.58-68
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• 2022

Backgrounds/Aims: Mechanisms for the development of hepatocellular carcinoma (HCC) in hepatitis B virus (HBV)-infected patients remain unclear. The aim of the present study was to identify genes and pathways involved in the development of HBV-associated HCC. Methods: The GSE121248 gene dataset, which included 70 HCCs and 37 adjacent liver tissues, was downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) in HCCs and adjacent liver tissues were identified. Gene ontology and Kyoto Encyclopedia of Genes and Genome pathway enrichment analyses were then performed. Results: Of 134 DEGs identified, 34 were up-regulated and 100 were down-regulated in HCCs. The 34 up-regulated DEGs were mainly involved in nuclear division, organelle fission, spindle and midbody formation, histone kinase activity, and p53 signaling pathway, whereas the 100 down-regulated DEGs were involved in steroid and hormone metabolism, collagen-coated extracellular matrix, oxidoreductase activity, and activity on paired donors, including incorporation or reduction of molecular oxygen, monooxygenase activity, and retinol metabolism. Analyses of protein-protein interaction networks with a high degree of connectivity identified significant modules containing 14 hub genes, including ANLN, ASPM, BUB1B, CCNB1, CDK1, CDKN3, ECT2, HMMR, NEK2, PBK, PRC1, RACGAP1, RRM2, and TOP2A, which were mainly associated with nuclear division, organelle fission, spindle formation, protein serine/threonine kinase activity, p53 signaling pathway, and cell cycle. Conclusions: This study identified key genes and carcinogenic pathways that play essential roles in the development of HBV-associated HCC. This may provide important information for the development of diagnostic and therapeutic targets for HCC.

• Tuberculosis and Respiratory Diseases
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• v.50 no.4
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• pp.450-461
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• 2001

Background : The underlying pathogenesis of radiation-induced lung fibrosis (RTLF) has not been very well defined. However, the role of TGF-$\beta$ in the generation of RTLF has been a major focus because there is an increase in the expression of both the TGF-${\beta}m$-RNA and its protein preceding RTLF lesions. The down stream signal after a TGF-$\beta$ stimulated lung fibrosis includes the activation of many mediators such as Smad and c-Jun N-terminal kinase (JNK) through TAK1. It is we hypothesized that JNK activation may play a pivotal role in RTLF pathogenesis through increased transcription of the fibrogenic cytokines. The present study evaluates JNK activity in alveolar macrophages after irradiation and the relationship between JNK activity and the amount of collagen in the lung tissues. Methods : C57BL/6 mice(20-25 gr, males) received chlorotetracycline(2g/L) in their drinking water 1 week prior to irradiation and continuously there after. The mice were irradiated once with 1400 cGy of $60CO{\gamma}$-ray over the whole chest. The cellular composition of the whole lung bronchoalveoalr lavage fluids(BALF), elastin expression in the lung tissues, the level of hydroxyproline in lung tissues, and an in vitro JNK assay was measured before irradiation and one, four, and eight weeks after irradiation (RT). Results : The volumes of BALF retrieved from instilled 4 mL of saline with 2% heparin were 3.7-3.8 mL for each group. The cell numbers were similar before($4.1{\times}10^4{\pm}0.5{\times}10^4/mL$) and 1 week($3.1{\times}10^4{\pm}0.5{\times}10^4/mL$) after RT. At four and eight weeks after RT, the cell number reached to $14.0{\times}10^4{\pm}1.5{\times}10^4mL$ and $10.0{\times}10^4{\pm}1.3{\times}10^4/mL$, respectively. There we no changes in the lymphocytes and neutrophils population observed in the BALF after RT. The H-E stain of the lung tissues did not show any structural and fibrotic change in the lung tissues at 4 and 8 weeks after RT. In addition, the amount of elastin and collagen were not different on Verhoeff staining of the lung tissues before RT to eight weeks after RT. The hydroxyproine content was measured with the left lung dissected from the left main bronchus. The lung were homogenized and hydrolyzed with 6 N Hel for 12 hours at $110^{\circ}C$ then measured as previously described. The content of hydroxyproline, standardized with a lung protein concentration, reached a peak 4 weeks after RT, and thereafter showed a plateau. AnIn vitro JNK assay using c-$Jun_{1-79}$-GST sepharose beads were performed with the alveolar macrophages obtained from the BAL. JNK activity was not detected prior to RT, However, the JNK activity increased from one week after RT and reached a peak four weeks after RT. Conclusion : JNK may be involved in the pathogenesis because the JNK activity showed similar pattern observed with the hydroxyproine content. However, it is necessary to clarify that the JNK increases the transcription of fibrogenic cyiokines through the transcription factor.

• Animal cells and systems
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• v.5 no.1
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• pp.71-75
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• 2001

Spin is an abundant maternal transcript comprising up to 0.2% of the total mRNA stock in mouse oocyte, whose protein product is associated with the meiotic spindle. We have identified a new isoform of Spin transcript containing a distinct 5'-untranslated region and the N-terminus of encoded protein. Northern blot and RT-PCR analysis showed that the new isoform is expressed in embryos and most of adult tissues, while the previously identified transcript is expressed solely in mouse oocyte. We thus designated these two Spin isoforms as somatic type and oocyte type, respectively. To investigate the underlying mechanism for the differential expression, genomic structure of Spin was examined. Spin exists as multiple copies in the genome, some of which appears to be pseudogenes, and characterization of Spin genomic clones indicates that oocyte- and somatic-isoforms were generated by alternative splicing. The complex organization of Spin genomic locus and its multifaceted control of expression provide a good model to study the molecular mechanisms of elaborate genome usage in mammals.

• BMB Reports
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• v.42 no.9
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• pp.568-573
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• 2009

Fatty acid oxidation (FAO) defects cause abnormal lipid accumulation in various tissues, which provides an opportunity to uncover novel genes that are involved in lipid metabolism. During a gene expression study in the riboflavin deficient induced FAO disorder in the chicken, we discovered the dramatic increase in mRNA levels of an uncharacterized gene, ANKRD9. No functions have been ascribed to ANKRD9 and its orthologs, although their sequences are well conserved among vertebrates. To provide insight into the function of ANKRD9, the expression of ANKRD9 mRNA in lipidperturbed paradigms was examined. The hepatic mRNA level of ANKRD9 was repressed by thyroid hormone ($T_3$) and fasting, elevated by re-feeding upon fasting. However, ANKRD9 mRNA level is reduced in response to apoptosis. Transient transfection assay with green fluorescent protein tagged- ANKRD9 showed that this protein is localized within the cytoplasm. These findings point to the possibility that ANKRD9 is involved in intracellular lipid accumulation.