• Korean Journal of Agricultural Science
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• v.44 no.2
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• pp.145-180
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• 2017

Alternanthera mosaic virus (AltMV) is a member of the genus Potexvirus which has been known for less than twenty years, and has been detected in Australasia, Europe, North and South America, and Asia. The natural host range to date includes species in at least twenty-four taxonomically diverse plant families, with species in at least four other families known to be infected experimentally. AltMV has been shown to differ from Potato virus X (PVX), the type member of the genus Potexvirus, in a number of ways, including the subcellular localization of the Triple Gene Block 3 (TGB3) protein and apparent absence of interactions between TGB3 and TGB2. Differences between AltMV variants have allowed identification of viral determinants of pathogenicity, and identification of residues involved in interactions with host proteins. Infectious clones of AltMV differing significantly in symptom severity and efficiency of RNA silencing suppression have been produced, suitable either for high level protein expression (with efficient RNA silencing suppression) or for Virus-Induced Gene Silencing (VIGS; with weaker RNA silencing suppression), demonstrating a range of utility not available with most other plant viral vectors. The difference in silencing suppression efficiency was shown to be due to a single amino acid residue substitution in TGB1, and to differences in subcellular localization of TGB1 to the nucleus and nucleolus. The current state of knowledge of AltMV biology, including host range, strain differentiation, host interactions, and utility as a plant viral vector for both protein expression and VIGS are summarized.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.13
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• pp.5233-5237
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• 2014

Epigenetic modifications of tumour suppressor genes are involved in all kinds of human cancer. Aberrant promoter methylation is also considered to play an essential role in development of lung cancer, but the pathogenesis remains unclear.We collected the data of 112 subjects, including 56 diagnosed patients with lung cancer and 56 controls without cancer. Methylation of the FHIT, RASSF1A and RAR-${\beta}$ genes in DNA from all samples and the corresponding gene methylation status were assessed using the methylation-specific polymerase chain reaction (PCR, MSP). The results showed that the total frequency of separate gene methylation was significantly higher in lung cancer compared with controls (33.9-85.7 vs 0 %) (p<0.01).Similar outcomes were obtained from the aberrant methylation of combinations of any two or three genes (p<0.01). There was a tendency that the frequency of combinations of any two or three genes was higher in stage I+II than that in stage III+IV with lung cancer. However, no significant difference was found across various clinical stages and clinic pathological gradings of lung cancer (p>0.05).These observations suggest that there is a significant association of promoter methylation of individual genes with lung cancer risk, and that aberrant methylation of combination of any two or three genes may be associated with clinical stage in lung cancer patients and involved in the initiation of lung cancer tumorigenesis. Methylation of FHIT, RASSF1A and $RAR{\beta}$ genes may be related to progression of lung oncogenesis.

• Preventive Nutrition and Food Science
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• v.8 no.4
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• pp.390-394
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• 2003

In the post-genome period, the technique for identifying gene expression has been progressed to high throughput screening. In the field of molecular nutrition, the use of screening techniques to clarify molecular function of specific nutrients would be very advantageous. In this study, we have evaluated Zn-regulated gene expression in Zn-deficient, homocystein-treated EA.hy926 cells, using cDNA microarray, which can be used to screen the expression of many genes simultaneously. The information obtained can be used for preliminary assessment of molecular and signaling events modulated by Zn under pro-atherogenic conditions. EA.hy926 cells derived from human umbilical vein endothelial cells were cultured in Zn-adequate (control, 15 $\mu$M Zn) or Zn-deficient (experimental, 0 $\mu$M Zn) Dulbecco's MEM media under high homocysteine level (100 $\mu$M) for 3 days of post-confluency. Cells were harvested and RNA was extracted. Total RNA was reverse-transcribed and the synthesized cDNA was labeled with Cy3 or Cy5. Fluorescent labeled cDNA probe was applied to microarray slides for hybridization, and the slide was then scanned using a fluorescence scanner. The expression of seven genes was found to be significantly decreased, and one significantly increased, in response to treatment of EA.hy926 cells with Zn-deficient medium, compared with Zn-supplemented medium. The upregulated genes were oncogenes and tumor suppressor genes, cell cycle-related genes and transporter genes. The down-regulated gene was RelB, a component of the NF-kappaB complex of transcription factors. The results of this study imply the effectiveness of cDNA microarray for expression profiling of a singly nutrient deficiency, namely Zn. Furthur study, using tailored-cDNA array and vascular endothelial cell lines, would be beneficial to clarify the molecular function of Zn in atherosclerosis, more in detail.

• International journal of thyroidology
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• v.11 no.2
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• pp.123-129
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• 2018

Background and Objectives: Hypermethylation of the tumor suppressor gene RASSF1A and activating mutation of BRAF gene have been recently reported in thyroid cancers. To investigate the role of these two epigenetic and genetic alterations in thyroid tumor progression, methylation of RASSF1A and BRAF mutation were examined in thyroid tumors. Materials and Methods: During 2007 to 2017, 69 papillary carcinomas, 18 nodular hyperplasia, 3 follicular carcinomas, and 13 follicular adenomas were selected. The methylation-specific polymerase chain reaction (MSP) technique was used in detecting RASSF1A methylation and polymerase chain reaction (PCR)-single-stranded conformation polymorphism and sequencing were used for BRAF gene mutation study. Results: The hypermethylation of the RASSF1A gene was found in 84.6%, 100% and 57.9% of follicular adenomas, follicular carcinomas, and papillary carcinomas, respectively. Nodular hyperplasia showed a hypermethylation in 33.3%. The BRAF mutation at V600E was found in 60.7% of papillary carcinoma and 27.0% of nodular hyperplasia, but none of follicular neoplasms. The BRAF mutation was correlated with the lymph node metastasis and MACIS clinical stage. There is an inverse correlation between RASSF1A methylation and BRAF mutation in thyroid lesions. Conclusion: Epigenetic inactivation of RASSF1A through aberrant methylation is considered to be an early step in thyroid tumorigenesis, and the BRAF mutation plays an important role in the carcinogenesis of papillary carcinoma, providing a genetic marker.

• Clinical and Experimental Pediatrics
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• v.55 no.1
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• pp.18-23
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• 2012

Purpose: Transforming growth factor beta receptor 2 ($TGFBR2$) is a tumor suppressor gene that plays a role in the differentiation of striated cells and remodeling of coronary arteries. Single nucleotide polymorphisms (SNPs) of this gene are associated with Marfan syndrome and sudden death in patients with coronary artery disease. Cardiovascular remodeling and T cell activation of $TGFBR2$ gene suggest that the $TGFBR2$ gene SNPs are related to the pathogenesis of Kawasaki disease (KD) and coronary artery lesion (CAL). Methods: The subjects were 105 patients with KD and 500 healthy adults as controls. Mean age of KD group was 32 months age and 26.6% of those had CAL. We selected $TGFBR2$ gene SNPs from serum and performed direct sequencing. Results: The sequences of the eleven SNPs in the $TGFBR2$ gene were compared between the KD group and controls. Three SNPs (rs1495592, rs6550004, rs795430) were associated with development of KD ($P$=0.019, $P$=0.026, $P$=0.016, respectively). One SNP (rs1495592) was associated with CAL in KD group ($P$=0.022). Conclusion: Eleven SNPs in $TGFBR2$ gene were identified at that time the genome wide association. But, with the change of the data base, only six SNPs remained associated with the $TGFBR2$ gene. One of the six SNPs (rs6550004) was associated with development of KD. One SNP associated with CAL (rs1495592) was disassociated from the $TGFBR2$ gene. The other five SNPs were not functionally identified, but these SNPs are notable because the data base is changing. Further studies involving larger group of patients with KD are needed.

• Proceedings of the Korean Society for Bioinformatics Conference
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• 2005.09a
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• pp.366-370
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• 2005

Tissue microarry is one of the high throughput technologies in the post-genomic era. Using tissue microarray, the researchers are able to investigate large amount of gene expressions at the level of DNA, RNA, and protein The important aspect of tissue microarry is its ability to assess a lot of biomarkers which have been used in clinical practice. To manipulate the categorical data of tissue microarray, we applied Bayesian network classifier algorithm. We identified that Bayesian network classifier algorithm could analyze tissue microarray data and integrating prior knowledge about gastric cancer could achieve better performance result. The results showed that relevant integration of prior knowledge promote the prediction accuracy of survival status of the immunohistochemical tissue microarray data of 18 tumor suppressor genes. In conclusion, the application of Bayesian network classifier seemed appropriate for the analysis of the tissue microarray data with clinical information.

• Genomics & Informatics
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• v.11 no.1
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• pp.38-45
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• 2013

In cancer genome studies, the annotation of newly detected oncogene/tumor suppressor gene candidates is a challenging process. We propose using concept lattice analysis for the annotation and interpretation of genes having candidate somatic mutations in whole-exome sequencing in acute myeloid leukemia (AML). We selected 45 highly mutated genes with whole-exome sequencing in 10 normal matched samples of the AML-M2 subtype. To evaluate these genes, we performed concept lattice analysis and annotated these genes with existing knowledge databases.

• Biomedical Science Letters
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• v.12 no.4
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• pp.385-391
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• 2006

Heterotrimeric GTP binding proteins (G proteins) mediate signals generated by neurotransmitters and hormones Among G proteins, Go is found in a large quantity in brain and growth cone membranes of neurons. In spite of its abundance in neurons, the role of Go is not fully understood. In our previous study, we identified promyelocytic leukemia zinc finger protein (PLZF) as an interacting partner of alpha subunit of Go ($Go{\alpha}$) and confirmed their interaction employing several biochemical assays. To date, it is reported that PLZF functioned as a cell growth suppressor and a transcription repressor. To determine effect of $Go{\alpha}$ and PLZF interaction on the cellular function of PLZF, we performed luciferase reporter gene assay and BrdU incorporation assay. Co-expression of $Go{\alpha}$ and PLZF synergistically increased the effect of PLZF alone. These results suggest that $Go{\alpha}$ may act as cellular activator of PLZF. This novel feature of Go may provide insights into understanding diverse role of Go-coupled receptor as well as its cellular actions.

• BMB Reports
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• v.38 no.5
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• pp.619-623
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• 2005

The efficacy of chemotherapeutic agents on tumor cells has been shown to be modulated by tumor suppressor gene p53 and its target genes such as Bcl-2 family members (Bax, Noxa, and PUMA). However, various chemotherapeutic agents can induce cell death in tumor cells that do not express the functional p53, suggesting that some chemotherapeutic agents may induce cell death in a p53-independent pathway. Here we showed that etoposide can induce the similar degree of cell death in p53-deficient HCT 116 cells, whereas 5'-FU-mediated cell death is strongly dependent on the existence of functional p53 in HCT 116 cells. Further, we provide the evidence that etoposide can induce the cytochrome c release from isolated mitochondria, and etoposide-induced cytochrome c release is not accompanied with the large amplitude swelling of mitochondria. These data suggest that etoposide can directly induce the mitochondrial dysfunction irrespective of p53 status, and it may, at least in part, account for the p53-independent pathway in cell death induced by chemotherapeutic agents.

• BMB Reports
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• v.49 no.7
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• pp.357-358
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• 2016

Merlin, encoded by the NF2 gene, is a tumor suppressor that exerts its function via inhibiting mitogenic receptors at the plasma membrane. Although multiple mutations in Merlin have been identified in Neurofibromatosis type II (NF2) disease, its molecular mechanism is not fully understood. Here, we show that Merlin interacts with LRP6 and inhibits LRP6 phosphorylation, a critical step for the initiation of Wnt signaling. We found that treatment of Wnt3a caused phosphorylation of Merlin by PAK1, leading to detachment of Merlin from LRP6 and allowing the initiation of Wnt/β-catenin signaling. A higher level of β-catenin was found in tissues from NF2 patients. Enhanced proliferation and migration caused by knockdown of Merlin in glioblastoma cells were inhibited by suppression of β-catenin. Conclusively, these results suggest that sustained Wnt/β-catenin signaling activity induced by abrogation of Merlin-mediated inhibition of LRP6 phosphorylation might be a cause of NF2 disease.