• Experimental and Molecular Medicine
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• v.50 no.12
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• pp.4.1-4.19
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• 2018

Transforming growth factor $(TGF)-{\beta}$ signaling is increasingly recognized as a key driver in cancer. In progressive cancer tissues, $TGF-{\beta}$ promotes tumor formation, and its increased expression often correlates with cancer malignancy. In this study, we utilized adenoviruses expressing short hairpin RNAs against $TGF-{\beta}1$ and $TGF-{\beta}2$ to investigate the role of $TGF-{\beta}$ downregulation in cancer cell death. We found that the downregulation of $TGF-{\beta}$ increased the phosphorylation of several SAPKs, such as p38 and JNK. Moreover, reactive oxygen species (ROS) production was also increased by $TGF-{\beta}$ downregulation, which triggered Akt inactivation and NOX4 increase-derived ROS in a cancer cell-type-specific manner. We also revealed the possibility of substantial gene fluctuation in response to $TGF-{\beta}$ downregulation related to SAPKs. The expression levels of Trx and GSTM1, which encode inhibitory proteins that bind to ASK1, were reduced, likely a result of the altered translocation of Smad complex proteins rather than from ROS production. Instead, both ROS and ROS-mediated ER stress were responsible for the decrease in interactions between ASK1 and Trx or GSTM1. Through these pathways, ASK1 was activated and induced cytotoxic tumor cell death via p38/JNK activation and (or) induction of ER stress.

• Biomolecules & Therapeutics
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• v.27 no.6
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• pp.553-561
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• 2019

Rab25, a member of the Rab11 small GTPase family, is central to achieving cellular polarity in epithelial tissues. Rab25 is highly expressed in epithelial cells of various tissues including breast, vagina, cervix, the gastrointestinal tract, and skin. Rab25 plays key roles in tumorigenesis, mainly by regulating epithelial differentiation and proliferation. However, its role in skin physiology is relatively unknown. In this study, we demonstrated that Rab25 knock-out (KO) mice show a skin barrier dysfunction with high trans-epidermal water loss and low cutaneous hydration. To examine this observation, we investigated the histology and epidermal differentiation markers of the skin in Rab25 KO mice. Rab25 KO increased cell proliferation at the basal layer of epidermis, whereas the supra-basal layer remained unaffected. Ceramide, which is a critical lipid component for skin barrier function, was not altered by Rab25 KO in its distribution or amount, as determined by immunohistochemistry. Notably, levels of epidermal differentiation markers, including loricrin, involucrin, and keratins (5, 14, 1, and 10) increased prominently in Rab25 KO mice. In line with this, depletion of Rab25 with single hairpin RNA increased the expression of differentiation markers in a human keratinocyte cell line, HaCaT. Transcriptomic analysis of the skin revealed increased expression of genes associated with skin development, epidermal development, and keratinocyte differentiation in Rab25 KO mice. Collectively, these results suggested that Rab25 is involved in the regulation of epidermal differentiation and proliferation.

• Molecules and Cells
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• v.44 no.7
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• pp.481-492
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• 2021

Tribbles homolog 2 (TRIB2) is implicated in tumorigenesis and drug resistance in various types of cancers. However, the role of TRIB2 in the regulation of tumorigenesis and drug resistance of cancer stem cells (CSCs) is still elusive. In the present study, we showed increased expression of TRIB2 in spheroid-forming and aldehyde dehydrogenase-positive CSC populations of A2780 epithelial ovarian cancer cells. Short hairpin RNA-mediated silencing of TRIB2 expression attenuates the spheroid-forming, migratory, tumorigenic, and drug-resistant properties of A2780 cells, whereas overexpression of TRIB2 increases the CSC-like characteristics. TRIB2 overexpression induced GSK3β inactivation by augmenting AKT-dependent phosphorylation of GSK3β at Ser9, followed by increasing β-catenin level via reducing the GSK3β-mediated phosphorylation of β-catenin. Treatment of TRIB2-ovexpressed A2780 cells with the phosphoinositide3-kinase inhibitor LY294002 abrogated TRIB2-stimulated proliferation, migration, drug resistance of A2780 cells. These results suggest a critical role for TRIB2 in the regulation of CSC-like properties by increasing the stability of β-catenin protein via the AKT-GSK3β-dependent pathways.

• The Journal of Korean Institute of Information Technology
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• v.17 no.3
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• pp.43-50
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• 2019

In this paper, we propose a S-band oscillator with a reduced electrical size by applying a vertical split ring resonator(VSRR). The VSRR is a type of split ring resonator that operates as a resonator by the capacitance and inductance generated between the microstrip lines arranged on the top and bottom of the dielectric substrate and it has an advantage that the electrical size of the resonance circuit can be reduced as compared with the conventional ring resonator. In this paper, we design a VSRR operating over S-band and an oscillator using the VSRR as the resonant circuit. The proposed oscillator showed the output of 5.9dBm at 2.4HGz and showed the phase noise characteristics of -112.58dBc at 100KHz offset frequency and -117.85dBc at 1MHz offset.

• Proceedings of the Korean Society of Plant Pathology Conference
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• 1994.06a
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• pp.86-102
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• 1994

To understand the molecular structure and pathogenesis mechanism of Korean garlic viruses, we have isolate cDNA clones for garlic viruses. The partial nucleotide sequences of 24 cDNA clones were determined and that of six clones containing poly (A) tail were compared with those of other plant viruses. One of those clones, V9 has 81.8% similarity in nucleotide sequence and 93.0% in deduced amino acid sequence, respectively, to the coat protein gene for garlic mosaic virus (GMV). Northern blot analysis with the clone V9 demonstrated that the genome of GMV is 7.8 kb long and has poly (A) tail. The anti-coat protein antibody for GMV recognizes 35 kDa polypeptide which could be the coat protein of GMV from infected garlic leaf extract or virus preparation. Clone G7 has about 62% of deduced amino acid sequence identity with the members of potyvirus group. Northern blot analysis with the clone G7 demonstrated that the genome of the potyvirus I garlic is 9.0 kb long and has poly (A) tail. The third clone, S81, shows 42% amino acid identity to the potexvirus. The other clones are under the characterization. To test the possibility of producing garlic virus resistant plant, we have designed a hairpin type ribozyme to cleave V9 RNA at the middle of the coat protein gene. From the cleavage reactions in vitro with two different sizes of RNA substrates, V9SUB (144 nucleotides) and V9 RNA (1,361 nucleotides), the ribozyme can cleave V9 sequence effectively at the predicted site. To study the activity of the ribozyme in vivo, plant transformation is in progress. Further possibilities to produce garlic virus resistant plant will be discussed.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.16
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• pp.7205-7210
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• 2015

Background: In this study, influence caused by expression plasmids of connective tissue growth factor (CTGF) and tissue inhibitor of metalloproteinase-1 (TIMP-1) short hairpin RNA (shRNA) on mRNA expression of CTGF,TIMP-1,procol-${\alpha}1$ and PCIII in hepatic tissue with hepatic fibrosis, a precancerous condition, in rats is analyzed. Materials and Methods: To screen and construct shRNA expression plasimid which effectively interferes RNA targets of CTGF and TIMP-1 in rats. 50 cleaning Wistar male rats are allocated randomly at 5 different groups after precancerous fibrosis models and then injection of shRNA expression plasimids. Plasmid psiRNA-GFP-Com (CTGF and TIMP-1 included), psiRNA-GFP-CTGF, psiRNA-GFP-TIMP-1 and psiRNA-DUO-GFPzeo of blank plasmid are injected at group A, B, C and D, respectively, and as model control group that none plasimid is injected at group E. In 2 weeks after last injection, to hepatic tissue at different groups, protein expression of CTGF, TIMP-1, procol-${\alpha}1$ and PC III is tested by immunohistochemical method and,mRNA expression of CTGF,TIMP-1,procol-${\alpha}1$ and PCIII is measured by real-time PCR. One-way ANOVA is used to comparison between-groups. Results: Compared with model group, there is no obvious difference of mRNA expression among CTGF,TIMP-1,procol-${\alpha}1$, PC III and of protein expression among CTGF, TIMP-1, procol-${\alpha}1$, PC III in hepatic tissue at group injected with blank plasmid. Expression quantity of mRNA of CTGF, TIMP-1, procol-${\alpha}1$ and PCIII at group A, B and C decreases, protein expression of CTGF, TIMP-1, procol-${\alpha}1$, PC III in hepatic tissue is lower, where the inhibition of combination RNA interference group (group A) on procol-${\alpha}1$ mRNA transcription and procol-${\alpha}1$ protein expression is superior to that of single interference group (group B and C) (P<0.01 or P<0.05). Conclusions: RNA interference on CTGF and/or TIMP-1 is obviously a inhibiting factor for mRNA and protein expression of CTGF, TIMP-1, procol-${\alpha}1$ and PCIII. Combination RNA interference on genes of CTGF and TIMP-1 is superior to that of single RNA interference, and this could be a contribution for prevention of precancerous condition.

• Journal of Periodontal and Implant Science
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• v.47 no.2
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• pp.116-131
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• 2017

Purpose: The entry of bacteria or harmful substances through the epithelial seal of human gingival keratinocytes (HGKs) in the junctional epithelium (JE) is blocked by specialized intercellular junctions such as E-cadherin junctions (ECJs). However, the influence of roughened substrates, which may occur due to apical migration of the JE, root planing, or peri-implantitis, on the development of the ECJs of HGKs remains largely unknown. Methods: HGKs were cultured on substrates with varying levels of roughness, which were prepared by rubbing hydrophobic polystyrene dishes with silicon carbide papers. The activity of c-Jun N-terminal kinase (JNK) was inhibited with SP600125 or by transfection with JNK short hairpin RNA. The development of intercellular junctions was analyzed using scanning electron microscopy or confocal laser scanning microscopy after immunohistochemical staining of the cells for E-cadherin. The expression level of phospho-JNK was assessed by immunoblotting. Results: HGKs developed tight intercellular junctions devoid of wide intercellular gaps on smooth substrates and on rough substrates with low-nanometer dimensions (average roughness $[Ra]=121.3{\pm}13.4nm$), although the ECJs of HGKs on rough substrates with low-nanometer dimensions developed later than those of HGKs on smooth substrates. In contrast, HGKs developed short intercellular junctions with wide intercellular gaps on rough substrates with mid- or high-nanometer dimensions ($Ra=505.3{\pm}115.3nm$, $867.0{\pm}168.6nm$). Notably, the stability of the ECJs was low on the rough substrates, as demonstrated by the rapid destruction of the cell junction following calcium depletion. Inhibition of JNK activity promoted ECJ development in HGKs. JNK was closely associated with cortical actin in the regulation of ECJs in HGKs. Conclusions: These results indicate that on rough substrates with nanometer dimensions, the ECJs of HGKs develop slowly or defectively, and that this effect can be reversed by inhibiting JNK.

• Journal of the Korean Society of Costume
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• v.18
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• pp.211-223
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• 1992

The results of the researches in the wig and the Boyo are as follows. The wig is to be classified into Bu, Pyun, Chah, Cheh, and kwik, Bu is an ornamental hairpin used by the empress, and it is decorated with Boyo. Pyun is a wig made of braided hair. Chah is made of Bal which is put together by its lenath, and it was also called Picheh or Pisuck. It is made, one by one, of hair of the convicts and the low-class people. 초도 has a meaning of toupee, and it is used to look beautiful with its thick black hair. Kwik is a wig made of hair as if it is weaved out of thread, and it is rounded with a wire. In ancient times, it was also called chah, Pi, or Pi People wore different wigs according to their class and the use, in order of Bu, Pyun, and Chah. There are remains of the Han Dynasty. Boyo, just like the wig, was originally a custom of the northern nomadic tribes which had been introduced to the later Han Dynasty. It is also called Cho Song and has a different meaning from the Boyo attached to a crown before the Han Dynasty. It became much more beautiful in the Which in period. Boyo gained its popularity by the women in Tang Dynasty, which is due to the influence by the customs of the western Ho tribe. The name of hairstyling using wigs in each period, and things such as hair, black thread, lignum, and paper were used as materials. Since the wig had differed according to the disparity in social standing it was prohibited to the general public, but it became in style later on. Wig also becomes popular in central Asia and gained its properity in the Tang Dynasty which is greatly influenced by the western countries. It is said in the records that the kobal Style had been exceedingly in fashion from the Ju to the Chung Dynasty, and the remains of the Han and Song Dynasty were found. times, it was also called chah, Pr, or period, and things such as hair, black thread, lignum, and paper were used as materials. Since the wig had differed according to the disparity in social standing, it was prohibited to the general public, but it became in style later on. Wig also becomes popular in central Asia and gained its prosperity in the Tang Dynasty which is greatly influenced by the western countries. It is said in the records that the kobal Style had been exceedingly in fashion from the Ju to the Chung Dynasty, and the remains of the Han and Song Dynasty were found.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.8
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• pp.3781-3789
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• 2012

Background: Pancreatic cancer is one of the most aggressive tumors with a dismal prognosis. The membrane cytoskeletal crosslinker Ezrin participates in several functions including cell proliferation, adhesion, motility and survival. There is increasing evidence that Ezrin is overexpressed in vast majority of malignant tumors and regulates tumor progression. However, its roles in pancreatic cancer remain elusive. Methods: Three pairs of specific Ezrin siRNAs were designed and synthetized and screened to determine the most efficient one for construction of a hairpin RNA plasmid targeting Ezrin. After transfection into the Panc-1 pancreatic cancer cell line, real-time quantitative PCR and Western blotting were performed to examine the expression of mRNA and protein. The MTT method was applied to examine the proliferation and the drug sensibility to Gemcitabine. Flow cytometry was used to assess the cycle and apoptosis, while capacity for invasion was determined with transwell chambers. Furthermore, we detected phosphorylated-Erk1/2 protein and phosphorylated-Akt protein by Western blotting. Results: Real-time quantitative PCR and Western blotting revealed that Ezrin expression was notably down-regulated at both mRNA and protein levels by RNA interference (P< 0.01). Proliferation was inhibited and drug resistance to gemcitabine was improved (P< 0.05). Flow cytometry showed that the proportion of cells in the G1/G0 phase increased (P< 0.01), and in G2/M and S phases decreased (P< 0.05), with no apparent differences in apoptosis (P> 0.05). The capacity for invasion was markedly reduced (P< 0.01). In addition, down-regulating Ezrin expression had no effect on phosphorylated-Akt protein (P>0.05), but could decrease the level of phosphorylated-Erk1/2 protein (P< 0.05). Conclusions: RNA interference of Ezrin could inhibit its expression in the pancreatic cancer cells line Panc-1, leading to a potent suppression of malignant behavior in vitro. Assessment of potential as a target for pancreatic cancer treatment is clearly warranted.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.5
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• pp.2045-2049
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• 2012

Objective: To investigate the effect of down-regulation of Sentrin/SUMO-specific protease 1 (SENP1) expression on the apoptosis of human Burkitt lymphoma cells (Daudi cells) and potential mechanisms. Methods: Short hairpin RNA (shRNA) targeting SENP1 was designed and synthesized and then cloned into a lentiviral vector. A lentiviral packaging plasmid was used to transfect Daudi cells (sh-SENP1-Daudi group). Daudi cells without transfection (Daudi group) and Daudi cells transfected with blank plasmid (sh-NC-Daudi group) served as control groups. Flow cytometry was performed to screen GFP positive cells and semiquantitative PCR and Western blot assays were employed to detect the inference efficiency. The morphology of cells was observed under a microscope before and after transfection. Fluorescence quantitative PCR and Western blot assays were conducted to measure the mRNA and protein expression of apoptosis related molecules (caspase-3, 8 and 9). After treatment with $COCl_2$ for 24 h, the mRNA and protein expression of hypoxia inducible factor -$1{\alpha}$ (HIF-$1{\alpha}$) was determined. Results: Sequencing showed the expression vectors of shRNA targeting SENP1 to be successfully constructed. Following screening of GFP positive cells by FCM, semiqualitative PCR showed the interference efficiency was $79.2{\pm}0.026%$. At 48 h after transfection, the Daudi cells became shrunken, had irregular edges and presented apoptotic bodies. Western blot assay revealed increase in expression of caspase-3, 8 and 9 with prolongation of transfection (P<0.05). Following hypoxia treatment, mRNA expression of HIF-$1{\alpha}$ remained unchanged in three groups (P>0.05) but the protein expression of HIF-$1{\alpha}$ markedly increased (P<0.05). However, in the sh-SENP1-Daudi group, the protein expression of HIF-$1{\alpha}$ remained unchanged Conclusion: SENP1-shRNA can efficiently inhibit SENP1 expression in Daudi cells. SENP1 inhibition may promote cell apoptosis. These findings suggest that SENP1 may serve as an important target in the gene therapy of Burkitts lymphoma.